Publication for NFKBIA and TNF

Species	Symbol	Function*	Entrez Gene ID*	Other ID	Gene coexpression	CoexViewer
hsa	NFKBIA	NFKB inhibitor alpha	4792			[link]
hsa	TNF	tumor necrosis factor	7124

Pubmed ID	Priority	Text
22722901	1.00	TNFalpha (15 ng/ml) was able to stimulate phosphorylation and subsequent degradation of IkappaBalpha when monitored by immunoblotting over 90 min.
	0.96	IkappaBalpha protein was almost undetectable after 30 min, and IkappaBalpha started reappearing around 90 min following TNFalpha addition, indicating a feedback regulation of IkappaBalpha synthesis.
	0.96	TNFalpha (15 ng/ml) was able to stimulate phosphorylation and subsequent degradation of IkappaBalpha when monitored by immunoblotting over 90 min.
	0.93	TNFalpha-induced activation of the canonical NF-kappaB pathway by measuring IkappaBalpha degradation, NF-kappaB nuclear localization, specific DNA-binding activity and transcriptional activity.
	0.93	TNFalpha-stimulated degradation of IkappaBalpha.
	0.92	TNFalpha induced the rapid phosphorylation and degradation of IkappaBalpha in H23 cells.
	0.80	TNFalpha-stimulated phosphorylation and degradation of IkappaBalpha.
	0.72	TNFalpha-stimulated phosphorylation and degradation of IkappaBalpha.
	0.68	IkappaBalpha transcript levels by TNFalpha.
	0.56	TNFalpha-induced IkappaBalpha degradation and subsequent NF-kappaB transcriptional activity.
19796012	0.98	TNFalpha-induced IkappaBalpha phosphorylation in macrophages.
	0.97	IkappaBalpha phosphorylation, but not in TNFalpha-induced IkappaBalpha-NFkappaB pathway in Raw264.7macrophages.
	0.97	TNFalpha-induced IkappaBalpha-NFkappaB pathway in Raw264.7 macrophages and suggest that IkappaBalpha phosphorylation by GRKs might be an essential step in this regulation.
	0.96	TNFalpha-induced IkappaBalpha phosphorylation tested as described earlier.
	0.96	TNFalpha-induced IkappaBalpha phosphorylation (at Ser32/36), but does inhibit LPS-induced IkappaBalpha phosphorylation, suggesting that in Raw264.7 macrophages, GRKs play the role of IkappaBalpha kinases selectively for TNFalpha signaling.
	0.96	TNFalpha-induced IkappaBalpha phosphorylation and degradation in macrophages
	0.95	TNFalpha caused a time-dependent increase in IkappaBalpha phosphorylation (at serines-32/36) and a subsequent decrease in IkappaBalpha levels (Fig 1).
	0.95	TNFalpha-induced IkappaBalpha phosphorylation compared to vector controls (Fig 2).
	0.95	TNFalpha-induced IkappaBalpha phosphorylation or whether p105 phosphorylation can also be regulated in a similar manner, we examined TNFalpha-induced p105 phosphorylation in control and GRK2/5 knockdown macrophages.
	0.95	TNFalpha-induced IkappaBalpha-NFkappaB pathway as well as its physiological gene expression target in macrophages.
	0.95	TNFalpha-induced IkappaBalpha phosphorylation is not significantly affected by knockdown of IKKbeta, suggesting that IKKbeta may be redundant in this system (Fig 9).
	0.94	TNFalpha-induced IkappaBalpha phosphorylation and degradation.
	0.94	IkappaBalpha kinases", IKKbeta may be dispensable in Raw264.7 cells, particularly for TNFalpha-induced IkappaBalpha phosphorylation.
	0.93	IkappaBalpha in the context of TNFalpha signaling in macrophages.
	0.93	TNFalpha-induced IkappaBalpha phosphorylation and degradation
	0.93	TNFalpha-induced IkappaBalpha-NFkappaB pathway, they are not involved in LPS-induced IkappaBalpha-NFkappaB signaling.
	0.92	TNFalpha-induced IkappaBalpha phosphorylation in Raw264.7 macrophages
	0.91	TNFalpha-induced IkappaBalpha phosphorylation and NFkappaB signaling.
	0.89	TNFalpha-induced IkappaBalpha-NFkappaB pathway.
	0.86	IkappaBalpha may be a substrate for GRKs in TNFalpha-induced NFkappaB signaling.
	0.85	IkappaBalpha phosphorylation/degradation, TNFalpha-induced p50 and p65 nuclear translocation were significantly inhibited in GRK2 knockdown cells compared to control cells (Fig 1D).
	0.85	IkappaBalpha-NFkappaB signaling and mediate TNFalpha-induced IkappaBalpha phosphorylation.
	0.84	TNFalpha-induced IkappaBalpha phosphorylation and degradation, NFkappaB activation, and expression of the NFkappaB-regulated gene, macrophage inflammatory protein-1beta.
	0.82	TNFalpha induced IkappaBalpha phosphorylation
	0.77	TNFalpha-induced IkappaBalpha phosphorylation (data not shown).
	0.70	TNFalpha-induced IkappaBalpha phosphorylation and degradation (Fig 3B, C & D).
	0.66	TNFalpha-induced IkappaBalpha phosphorylation and degradation
	0.62	IkappaBalpha phosphorylation and degradation leads to subsequent release and translocation of the NFkappaB subunits, primarily p50 and p65, we next examined the nuclear levels of the NFkappaB subunits in control and GRK2 knockdown cells before and after TNFalpha treatment.
	0.61	TNFalpha-induced IkappaBalpha phosphorylation (Ser32/36).
	0.54	IkappaBalpha phosphorylation (on Ser32/36) and therefore, suggest that LPS and TNFalpha signal to NFkappaB activation via different mechanisms in Raw264.7 macrophages.
23284737	0.98	IkappaBalpha to the action of 26S proteasome, contributing to the optimal control of NF-kappaB activity after TNFalpha-stimulation.
	0.98	TNFalpha-induced IkappaBalpha degradation and the activation of the NF-kappaB transcription factor.
	0.98	IkappaBalpha in a TNFalpha-mediated time-course response in HEK293 cells (Figure 4).
	0.97	IkappaBalpha after activation of the TNFalpha signalling pathway.
	0.96	IkappaBalpha behave as previously reported with a peak of ubiquitylated IkappaBalpha after 20 minutes of TNFalpha stimulation followed by a reduction at 60 minutes, even in the presence of the proteasome inhibitor MG132.
	0.95	TNFalpha-mediated NF-kappaB activation and degradation of IkappaBalpha.
	0.95	IkappaBalpha is detected after 20 minutes of TNFalpha stimulation (Figure 4C).
	0.95	IkappaBalpha is importantly reduced after 60 minutes of TNFalpha stimulation, even in the presence of proteasome inhibitors (Figure 4C).
	0.95	IkappaBalpha SUMOylation is at 60 minutes of TNFalpha-stimulation (Figure 3D and Figure 4).
	0.95	IkappaBalpha appear to be mainly mono-modified with SUMO-2, ubiquitin-IkappaBalpha and SUMO-2-IkappaBalpha are also polySUMOylated after 1hr pre-treatment with MG132 and TNFalpha stimulation (Figure 6C).
	0.93	IkappaBalpha SUMOylation correlates with a deficient TNFalpha-induced IkappaBalpha degradation and NF-kappaB activation.
	0.90	IkappaBalpha and activation of NF-kappaB mediated by TNFalpha.
	0.90	TNFalpha stimulation, IkappaBalpha accumulated as both ubiquitylated and SUMOylated forms.
	0.89	TNFalpha stimulation, mono-modified forms of endogenous IkappaBalpha with SUMO-2 and SUMO-3 (Figure 3A).
	0.88	IkappaBalpha-SV5 WT or mutated on K21 and K22 in the presence of His6Ubiquitin, His6-SUMO2 and His6-SUMO3, pre-treated with MG132 and stimulated with TNFalpha.
	0.87	IkappaBalpha containing SUMO-2/3 and ubiquitin after TNFalpha stimulation.
	0.85	TNFalpha stimulation the levels of ubiquitylated IkappaBalpha dramatically decreased, while SUMOylated IkappaBalpha maintained a modest but consistent increase as compared to the unstimulated condition (Figure 3D).
	0.85	IkappaBalpha after proteasome inhibition with MG132 and TNFalpha-stimulation (data not shown).
	0.84	TNFalpha-stimulation thus coinciding with the peak of ubiquitylated IkappaBalpha, allowing us to analyse the contribution of SUMO-2/3 in the formation of hybrid chains.
	0.69	IkappaBalpha stability after cell activation with TNFalpha, we used a tool recently developed by our group to capture endogenous ubiquitylated proteins.
	0.67	TNFalpha, we can observe an accumulation of high molecular weight bands, suggesting that polyubiquitylation and polySUMOylation of IkappaBalpha (mainly with SUMO-2) are significantly enhanced in this condition (Figure 2B right panel).
	0.64	IkappaBalpha was only evident in cells transiently expressing His6-ubiquitin after 15 min stimulation with TNFalpha and in the presence of MG132 (Figure 3A).
	0.62	IkappaBalpha after TNFalpha-stimulation analysed by immunoprecipitations with anti-IgG control, anti-ubiquitin, anti-IkappaBalpha and anti-SUMO-2/3 antibodies.
	0.62	TNFalpha drives an efficient ubiquitin chain extension of both ubiquitin-IkappaBalpha and SUMO-2-IkappaBalpha fusions, far superior to the one observed with IkappaBalphaWT or SUMO-1-IkappaBalpha fusion.
26463447	0.98	IkappaBalpha and RelA to become simultaneously phosphorylated in the cytosol in response to TNF and their phosphorylation to occur within the NF-kappaB/RelA-IkappaBalpha complex, we next analysed the dependence of RelA phosphorylation on canonical IKKs (the IKK complex) and IKK-related kinases (IKKepsilon and TBK1).
	0.97	TNF-induced IkappaBalpha degradation and the release of RelA
	0.97	IkappaBalpha degradation because of inhibition of CRL1beta-TrCP neddylation, and thus its catalytic activation, coincided with nearly complete inhibition of TNF-induced RelA nuclear accumulation (Fig. 1E).
	0.97	TNF-induced phosphorylation and degradation of IkappaBalpha in the cytosol were completely inhibited in cells pretreated with TPCA-1 (Fig. S2A), an inhibitor of canonical IKKs with high selectivity for IKKbeta 68, demonstrating this inhibitor to efficiently block kinase activity of the IKK complex, being responsible for IkappaBalpha phosphorylation in the canonical pathway of NF-kappaB activation 1, 6.
	0.97	IkappaBalpha with RelA in response to TNF.
	0.97	IkappaBalpha, in response to TNF or alternative agonists, is largely unexplored by now.
	0.95	IkappaBalpha and RelA expression, likely depending on p97/VCP-supported scheduled basal NF-kappaB activity, and the mechanism of TNF-induced NF-kappaB activation.
	0.94	TNF-induced IkappaBalpha phosphorylation/degradation and RelA phosphorylation/nuclear translocation, PI3K inhibitor wortmannin did not affect any of the cytoplasmic events (Fig. S2A).
	0.94	IkappaBalpha in response to TNF.
	0.90	IkappaBalpha, a bonafide substrate of CRL1beta-TrCP 52, 53 and phosphorylated isoforms of RelA, a substrate of CRL2SOCS1 10, 11, to already accumulate upon exposure of non-stimulated cells to MLN4924, a phenomenon previously noted in preclinical models of B-cell-like lymphoma 48, we next explored the impact of NAE inhibition on CRL-dependent proteolytic turnover of components of the NF-kappaB system during a time course of TNF stimulation.
	0.90	IkappaBalpha and p105) with efficient inhibition of TNF-induced RelA nuclear accumulation already implicated at this time that RelA phosphorylation by itself is likely insufficient to liberate RelA from its cytoplasmic anchor proteins, e.g. IkappaBalpha.
	0.90	TNF-induced association of p97/VCP with IkappaBalpha-Ub 29, 71, reciprocal IPs of both interaction partners were performed.
	0.85	IkappaBalpha and RelA and its phosphorylated isoforms, reciprocal IPs of both interaction partners were performed from cytosolic fractions of cells treated with MLN4924 prior to TNF stimulation.
	0.81	IkappaBalpha in response to TNF stimulation.
	0.77	IkappaBalpha in response to TNF stimulation in epithelial cells, we thus explored in this study (i) the impact of RelA phosphorylation on RelA association with IkappaBalpha before and after phosphorylation and ubiquitination of the latter, (ii) the kinase responsible for RelA phosphorylation, and (iii) the requirement of p97/VCP for IkappaBalpha degradation, liberation of RelA from IkappaBalpha and RelA nuclear translocation.
	0.72	TNF-induced degradation of IkappaBalpha and concomitant release and nuclear translocation of RelA. (A-C) Cullin neddylation is rapidly and efficiently inhibited by NAE inhibitor MLN4924.
	0.68	TNF stimulation was observed concomitant with a clear defect in the liberation of RelA from (ubiquitinated) IkappaBalpha 30 min.
	0.67	TNF-induced dissociation of the NF-kappaB/RelA-IkappaBalpha complex in epithelial cells, the timely and efficient degradation of ubiquitinated IkappaBalpha and the concomitant liberation of active NF-kappaB molecules, ready to enter the cell nucleus, we decided to initially make use of MLN4924, a potent small molecule inhibitor of the NEDD8-activating enzyme (NAE) 24.
	0.67	TNF-induced degradation of IkappaBalpha was efficiently inhibited in the cytosol, as expected.
	0.65	IkappaBalpha and RelA nuclear translocation in response to TNF.
	0.62	TNF-induced liberation of RelA from ubiquitinated IkappaBalpha.
	0.50	IkappaBalpha in vitro, as well as in cells stimulated with TNF, and to promote its UPP-dependent degradation in an in vitro assay 71.
25122471	0.98	IkappaBalpha, cells treated with TNFalpha showed decreased levels of IkappaBalpha (Fig. 4B).
	0.97	TNFalpha, fixed and stained with anti-IkappaBalpha or anti-I3L, an early poxvirus protein that is indicative of infection, and analyzed by flow cytometry.
	0.96	TNFalpha or IL-1beta accumulate phosphorylated IkappaBalpha, indicating that IkappaBalpha is stabilized and not degraded.
	0.95	TNFalpha or IL-1beta stimulation (shown in blue) inhibited the degradation of IkappaBalpha, as expected (Fig. 4C panel a and d).
	0.95	TNFalpha-stimulated mock-infected cells that were pre-treated with the proteasome inhibitor MG132 maintained IkappaBalpha levels (shown in blue) (Fig. 7A panel a).
	0.95	TNFalpha induced IkappaBalpha degradation.
	0.94	TNFalpha- and IL-1beta-stimulated IkappaBalpha degradation and subsequent nuclear translocation of NF-kappaB; however, deletion of the EVM005 F-box domain resulted in activation of NF-kappaB. ECTV devoid of EVM005, ECTV-Delta005, inhibited NF-kappaB activation.
	0.94	TNFalpha treatment, mock-infected cells showed phosphorylated IkappaBalpha, as indicated by a doublet, which was subsequently degraded (Fig. 1A and B).
	0.94	IkappaBalpha that were significantly decreased following TNFalpha or IL-1beta stimulation, as indicated by a leftward shift on the histogram (shown in green) (Fig. 4C panels a and d).
	0.93	TNFalpha- and IL-1beta-induced IkappaBalpha degradation
	0.92	TNFalpha-stimulated cells infected with ECTV-Delta005 or ECTV-005-rev also inhibited IkappaBalpha degradation (Fig. 7A panels c and d).
	0.91	TNFalpha or IL-1beta, Orthopoxvirus-infected cells displayed an accumulation of phosphorylated IkappaBalpha, indicating that NF-kappaB activation was inhibited during poxvirus infection.
	0.91	IkappaBalpha is catalyzed by the SCFbeta-TRCP ubiquitin ligase, we investigated the role of the ectromelia virus ankyrin/F-box protein, EVM005, in the regulation of NF-kappaB. Expression of Flag-EVM005 inhibited both TNFalpha- and IL-1beta-stimulated IkappaBalpha degradation and p65 nuclear translocation.
	0.91	TNFalpha stimulation, similar to IkappaBalpha.
	0.90	TNFalpha demonstrated that ectopic expression of EVM005 stabilized IkappaBalpha compared to the surrounding cells (Fig. 4A panel m-p).
	0.85	IkappaBalpha that decreased following TNFalpha stimulation (shown in green) (Fig. 7A panel a).
	0.84	TNFalpha or IL-1beta, and fixed and stained with anti-Flag and anti-IkappaBalpha, to detect EVM005 and IkappaBalpha, respectively.
	0.81	TNFalpha showed a typical pattern of IkappaBalpha degradation kinetics (Fig. 1A).
	0.72	TNFalpha and immunoblotted for anti-IkappaBalpha, anti-Flag to detect EVM005, and anti-beta-tubulin as a loading control.
	0.51	IkappaBalpha were unaffected by expression of Flag-EVM005(1-593) (Fig. 4A panel q-t); however, upon treatment with TNFalpha, IkappaBalpha was degraded, suggesting that the F-box domain was necessary for EVM005 to inhibit IkappaBalpha degradation (Fig. 4A panel u-x).
20696864	0.98	TNF-alpha promoter is unphosphorylated and can be removed by IkappaBalpha, the p65 recruited to IL-8 promoter is phosphorylated on S536, which decreases its affinity for IkappaBalpha and makes it unresponsive to the inhibition by nuclear IkappaBalpha (Table I).
	0.98	TNF-alpha, IL-1beta, or IL-6 promoters (Fig. 9), indicating that this phosphorylation may represent one of the mechanisms responsible for the gene-specific inhibition of NF-kappaB-dependent transcription by nuclear IkappaBalpha.
	0.97	TNF-alpha, the beta form of pro-IL-1 (IL-1beta), and IL-6 were inhibited by the leptomycin B-induced nuclear IkappaBalpha, IL-8 mRNA expression and cellular release were not significantly affected.
	0.97	IkappaBalpha induced by post-induction repression in the nucleus of U937 cells stimulated 6 h with LPS (Fig. 5) and with studies demonstrating that IkappaBalpha associates with DNA through p65 NF-kappaB. Importantly, LMB treatment that increases the nuclear accumulation of IkappaBalpha (Fig. 5A, 5B) inhibited the LPS-induced IkappaBalpha recruitment to TNF-alpha, IL-1beta, and IL-6 promoters (Fig. 7A-C), indicating that the LMB-induced nuclear IkappaBalpha inhibits transcription of these genes by removing p65 NF-kappaB from the NF-kappaB promoter sites.
	0.96	TNF-alpha, IL-1beta, and IL-6, but not IL-8 (Fig. 3) suggested that the inhibition of NF-kappaB-dependent transcription by nuclear IkappaBalpha is gene specific.
	0.96	TNF-alpha, IL-1beta, or IL-6, enrichment of IkappaBalpha at the IL-8 promoter was not markedly affected by LPS stimulation or by LMB treatment (Fig. 7D).
	0.94	TNF-alpha, IL-1beta, and IL-6 promoters was inhibited by the nuclear IkappaBalpha, p65 recruitment to IL-8 promoter was not repressed.
	0.93	IkappaBalpha proteins to TNF-alpha, IL-1beta, IL-6, and IL-8 promoters, we demonstrate in this paper that both p65 and p50 NF-kappaB are recruited to IL-1beta and IL-6 promoters in 6-h LPS-stimulated human macrophages, whereas TNF-alpha and IL-8 promoters contain predominantly p65 NF-kappaB (Fig. 7).
	0.90	IkappaBalpha, p50, and p65 recruitment to TNF-alpha (A), IL-1beta (B), IL-6 (C), and IL-8 (D) promoters was measured by ChIP analysis and quantified by real-time PCR.
	0.85	IkappaBalpha inhibits p65 NF-kappaB recruitment to TNF-alpha, IL-1beta, and IL-6 promoters (Fig. 6A-C), thus inhibiting transcription of these genes (Fig. 3A-C), it does not remove p65 NF-kappaB from IL-8 promoter (Fig. 6D) and does not inhibit IL-8 transcription (Fig. 3D).
	0.82	TNF-alpha release inhibition by LMB from stimulated human leukocytes and to test the hypothesis that inhibition of NF-kappaB-dependent transcription by nuclear IkappaBalpha is gene specific.
	0.81	TNF-alpha, IL-1beta, and IL-6 in LPS-stimulated human macrophages is inhibited by the nuclear IkappaBalpha, transcription of IL-8 is not.
	0.78	TNF-alpha promoter is inhibited by the LMB-induced nuclear IkappaBalpha, whereas the p65 recruitment to IL-8 promoter is not repressed.
	0.77	IkappaBalpha to TNF-alpha, IL-1beta, and IL-6 promoters compared with unstimulated cells (Fig. 7A-C).
	0.73	IkappaBalpha is able to remove transcriptionally active p65 NF-kappaB from TNF-alpha, IL-1beta, and IL-6 promoters, whereas it does not inhibit p65 binding to IL-8 promoter in LPS-stimulated macrophages.
	0.69	IkappaBalpha inhibited p65 NF-kappaB recruitment to the TNF-alpha but not the IL-8 promoter in LPS-stimulated human PBMCs (Fig. 8).
	0.68	TNF-alpha, IL-1beta, and IL-6 from LPS-stimulated U937 macrophages were greatly inhibited by the LMB-induced nuclear IkappaBalpha, IL-8 mRNA expression and cellular release were not significantly affected.
	0.56	TNF-alpha, IL-1beta, and IL-6 promoters is inhibited by the nuclear IkappaBalpha, recruitment to IL-8 promoter is not repressed.
	0.53	TNF-alpha and IL-8 promoters by nuclear IkappaBalpha in primary human PBMCs
22022389	0.98	IkappaBalpha resistance to TNFalpha-induced proteolysis, suggest reduced capacity to interact/get access to the proteasome.
	0.96	IkappaBalpha is stable after TNFalpha stimulation and does coexist with polyubiquitylated IkappaBalpha under the same conditions.
	0.95	IkappaBalpha mutant after TNFalpha stimulation in a situation where polyubiquitylated IkappaBalpha WT is well accumulated (Figure 3B).
	0.95	IkappaBalpha accumulated after proteasome inhibitor and TNFalpha treatment can be the result of proofreading mechanism acting on polyubiquitylated IkappaBalpha.
	0.93	IkappaBalpha is degraded after 20 minutes of TNFalpha-stimulation as it can be seen in the input (IN).
	0.93	IkappaBalpha fusion negatively affects TNF-induced NF-kappaB activity.
	0.92	IkappaBalpha is not destabilized by the induction with TNFalpha but it is slightly accumulated after treatment with MG132 (Figure 3A).
	0.90	IkappaBalpha stability is also reflected after signal-mediated stimulation, as this ubiquitin-IkappaBalpha fusion shows resistance to TNFalpha induced degradation (Figure 4C).
	0.88	IkappaBalpha remain very stable after 20 or 60 minutes of TNFalpha stimulation even in the presence of proteasome inhibitor (Figure 3A).
	0.84	IkappaBalpha resistant to TNFalpha-induced proteolysis, which is able to interact and repress DNA binding and NF-kappaB transcriptional activity.
	0.81	IkappaBalpha fusion became statistically significant after 6 hours of TNFalpha stimulation (Figure 6C).
	0.79	IkappaBalpha fusion, results presented here show that monoubiquitylated IkappaBalpha has an impact on basal and TNFalpha-induced NF-kappaB transcription.
	0.70	TNFalpha stimulation and MG132, modified forms of IkappaBalpha were captured using His6-Ubiquitin, His6-SUMO-1 or His6-SUMO-2 and nickel beads chromatography.
	0.66	IkappaBalpha is not sensitive to the TNFalpha-mediated degradation
	0.60	TNFalpha (tumor necrosis factor-alpha) ends with the activation of the IKK (IkappaBalpha Kinase) complex, composed by IKKalpha, IKKbeta and IKKgamma/NEMO .
28513540	0.98	TNF stimulation from inducing IkappaBalpha degradation and NF-kappaB activation.
	0.97	TNF-Induced IkappaBalpha Degradation
	0.97	IkappaBalpha degradation in response to TNF stimulation was still inhibited by ETEC FliC, even after hTLR5-Fc pre-incubation (Figure 2F).
	0.97	TNF-induced IkappaBalpha degradation.
	0.97	TNF-induced IkappaBalpha degradation.
	0.97	IkappaBalpha immunoreactivity in HCT-8 cells 24 h post-transfection of fliC truncations in the absence of TNF stimulation; (C) IkappaBalpha immunoreactivity in HCT-8 cells 24 h post-transfection of fliC truncations after TNF stimulation (20 ng/mL, 20 min).
	0.96	TNF stimulation or microbial infection, the IkappaB kinase (IKK) complex is activated and phosphorylates IkappaBalpha which is then polyubiquitinated and degraded, resulting in nuclear translocation of NF-kappaB subunits.
	0.96	IkappaBalpha immunoreactivity after incubating HCT-8 cells with WT and mutant ETEC supernatants (10 microg protein) and then stimulating the cells with TNF (20 ng/mL, 20 min); (B) Purified recombinant FliC resolved using 10% SDS-PAGE and Coomassie blue staining; (C) IkappaBalpha immunoreactivity after incubating HCT-8 cells with FliC-pET28a-BL21 (100 pg-10 microg) for 1.5 h followed by TNF stimulation (20 ng/mL, 20 min); (D) IkappaBalpha immunoreactivity after incubating HCT-8 cells with FliC-pET28a-ClearColi (100 pg-10 microg) for 1.5 h and then stimulating the cells with TNF (20 ng/mL, 20 min); (E) IkappaBalpha immunoreactivity after incubating HCT-8 cells with heated (100 C, 20 min), recombinant FliC (1 microg) for 1.5 h followed by TNF stimulation (20 ng/mL, 20 min); (F) IkappaBalpha immunoreactivity after pretreating HCT-8 cells with 1.5 microg/mL hTRL5-Fc for 1 h, followed by FliC (100 ng/mL, 90 min) and TNF (20 ng/mL, 20 min).
	0.95	TNF-induced IkappaBalpha degradation (Figure 4C).
	0.94	IkappaBalpha from TNF-induced degradation in a dose-dependent manner (Figure 2D).
	0.94	IkappaBalpha degradation in response to TNF stimulation (Figure 1 and Figure 2).
	0.93	IkappaBalpha immunoreactivity after incubating HCT-8 cells with ETEC H10407-M9 supernatant (0.1-10 microg protein) and then stimulating the cells with TNF (20 ng/mL, 20 min) Asterisks indicate significantly different IkappaBalpha abundance as compared with the 'TNF only' lane; (B) IkappaBalpha immunoreactivity after incubating HCT-8 cells with ETEC H10407-M9 supernatant (0.1-10 microg protein) and then stimulating the cells with TNF (20 ng/mL, 20 min); (C) IkappaBalpha immunoreactivity after incubating HCT-8 cells with ETEC H10407-RPMI1640 and ETEC H10407-M9 supernatants (10 microg protein) without TNF; (D) IkappaBalpha immunoreactivity after incubating HCT-8 cells with ETEC H10407-M9 supernatant FPLC fractions for 1.5 h and then stimulating the cells with TNF (20 ng/mL, 20 min); (E) Sliver staining of FPLC fractions E and F on 10% SDS-PAGE.
	0.88	IkappaBalpha degradation in response to TNF (Figure 3B), none of the truncated FliC proteins were active.
	0.84	IkappaBalpha degradation in response to TNF could be associated with TNFR internalization, as we had previously observed that blocking clathrin-dependent endocytosis affected the activity of the ETEC secreted factor (ESF).
	0.80	IkappaBalpha immunoreactivity after incubating HCT-8 cells with FliC truncations (1 microg) for 1.5 h followed by TNF stimulation (20 ng/mL, 20 min); (C) IkappaBalpha immunoreactivity after incubating HCT-8 cells with heated (100 C, 20 min) FliC (1 microg) followed by TNF stimulation (20 ng/mL, 20 min).
22684243	0.98	IkappaBalpha in TNFalpha-stimulated HEK293 cells
	0.98	TNFalpha-induced NF-kappaB activation by delaying the degradation of IkappaBalpha, but it did not inhibit TNFalpha-induced IkappaBalpha phosphorylation and IKK activation.
	0.98	H2O2 and TNFalpha, and its kinase activity was measured in a reaction mixture containing [gamma-32P]ATP and GST-IkappaBalpha (Figure 2).
	0.97	IkappaBalpha revealed that its degradation upon TNFalpha stimulation was blocked by pre-exposure to H2O2 (Figure 3A).
	0.97	IkappaBalpha phosphorylated at Ser-32 and Ser-36 using a phospho-specific antibody revealed that TNFalpha-induced IkappaBalpha phosphorylation was not inhibited by pre-exposure to H2O2.
	0.97	TNFalpha-induced activation of NF-kappaB in HEK293 cells by blocking the degradation of phosphorylated IkappaBalpha.
	0.97	TNFalpha in the presence of MG-132, high-molecular-weight poly-ubiquitinated IkappaBalpha appeared after 5 min and remained undegraded.
	0.96	IkappaBalpha, whereas proteasomal peptidase activities were not changed, indicating that transient oxidative stress temporally inhibits NF-kappaB activation by blocking IkappaBalpha ubiquitination in TNFalpha-stimulated HEK293 cells.
	0.95	TNFalpha in the presence of MG-132, the poly-ubiquitination of IkappaBalpha was obvious only after 30 min.
	0.94	TNFalpha stimulation, pre-exposure of cells to H2O2 significantly delayed IkappaBalpha degradation, whereas IkappaBalpha phosphorylation was not changed in the same cells (Figure 3B).
	0.91	TNFalpha-induced NF-kappaB activation by temporarily blocking the ubiquitination of phosphorylated IkappaBalpha, whereas IKK activity and IkappaBalpha phosphorylation remain largely intact in the same cells.
	0.79	TNFalpha in the absence of the proteasomal inhibitor MG-132 induced the time-dependent degradation of IkappaBalpha.
29734393	0.98	TNFalpha stimulation is due to a blockage of IkappaBalpha degradation, HeLa cells were infected with O. tsutsugamushi.
	0.97	TNFalpha-induced p65 accumulation in the nucleus and reduces NF-kappaB-dependent transcription in a manner that involves neither degradation of p65 nor inhibition of IkappaBalpha degradation and is therefore likely due to direct bacterial modulation of p65 itself.
	0.97	TNFalpha, p65 was detected in the nuclei of more than 80% of cells expressing Flag-BAP or GFP and almost none of the cells expressing Flag-IkappaBalpha SR.
	0.97	TNFalpha-induced IkappaBalpha dissociation from p65 proceeds normally in the presence of either Ank and that a Flag-Ank1/6:p65:IkappaBalpha ternary complex does not form.
	0.96	TNFalpha induced degradation of IkappaBalpha frees the p50/p65 dimer to translocate into the nucleus.
	0.95	IkappaBalpha SR abrogated TNFalpha-stimulated p65 nuclear accumulation, LMB eliminated this phenomenon (Figs 11 and S7).
	0.94	TNFalpha- and IL-1beta-induced IkappaBalpha degradation.
	0.83	IkappaBalpha levels are reduced to similar degrees in uninfected and infected cells upon TNFalpha stimulation.
	0.82	TNFalpha was present or not, but failed to precipitate endogenous IkappaBalpha in either condition.
	0.81	TNFalpha-stimulated IkappaBalpha degradation proceeds normally in O. tsutsugamushi infected cells, it can be inferred that the Ank1/Ank6 mechanism of action is distinct from the ectromelia virus F-box-containing Anks.
	0.78	IkappaBalpha from lysates of TNFalpha-exposed HeLa cells.
	0.57	IkappaBalpha SR as compared to Flag-BAP, whether exposed to TNFalpha or not (Fig 7A and 7B).
21602809	0.98	TNF-tolerized cells can contribute to induction of nontolerized genes, such as the early response gene NFKBIA that is rapidly activated by NF-kappaB with minimal additional activation requirements.
	0.97	I-kappaBalpha protein amounts were rapidly restored to prestimulation levels in TNF-tolerized macrophages (Fig. 3a, lanes 9-12).
	0.96	I-kappaBalpha 90 minutes after LPS stimulation of TNF-tolerized macrophages, and this nuclear accumulation was abrogated when GSK3 was inhibited (Fig. 5d).
	0.96	TNF-tolerized macrophages, NF-kappaB signaling is completely abrogated in TLR-tolerized cells, with minimal degradation of I-kappaBalpha, likely secondary to a strong block in proximal signaling.
	0.87	TNF-induced tolerance was distinct from TLR-induced tolerance as it was dependent on GSK3, which suppressed chromatin accessibility and promoted rapid termination of NF-kappaB signaling by augmenting negative feedback by A20 and I-kappaBalpha.
	0.85	I-kappaBalpha protein re-expression after LPS stimulation of TNF-tolerized macrophages.
	0.83	TNF-tolerized macrophages the initial phase of LPS-induced I-kappaBalpha degradation was nearly intact (Fig. 3a, lanes 9-12 vs. 5-8).
	0.83	TNF-tolerized cells (Fig. 6b), which provides an explanation for decreased I-kappaBalpha degradation.
	0.79	NFKBIA mRNA was induced after LPS stimulation of TNF-tolerized macrophages (Fig. 6a); thus NFKBIA is a nontolerizable gene.
	0.72	I-kappaBalpha in TNF-tolerized macrophages.
	0.50	TNF-induced tolerance at least in part by promoting rapid reaccumulation of newly synthesized I-kappaBalpha, thereby attenuating expression of NF-kappaB-dependent genes.
24224954	0.98	TNF resulted in more persistentstimulation of the NFkappaB signaling pathway, as evidenced by continuing degradation of IkappaB-alpha and increasingly high levels of p65 in the nuclear fractions over the time course of the exposure (Fig. 4).
	0.97	TNF) of cytosolic IkappaB-alpha and nuclear p65 were lower and higher, respectively, than in control cells.
	0.97	TNF stimulation, then phosphorylation of IkappaB-alpha could also be affected.
	0.97	TNF-induced p65 phosphorylation was compared to the time course of IkappaB-alpha phosphorylation (Fig. 6).
	0.97	TNF-induced degradation of IkappaB-alpha and nuclear translocation of NFkappaB is not inhibited by SAH.
	0.90	IkappaB-alpha and translocation of NFkappaB to nucleus, were not completely blocked in cells with high SAH levels, but the expression of NFkappaB-dependent genes was no longer inducible upon TNF exposure.
	0.89	TNF-induced expression of IkappaB-alpha, A20 and IL-8 was inhibited in hepatocytes pre-treated with Ado+Hcy (Fig. 3C).
	0.89	IkappaB-alpha occurred 5 minutes after TNF stimulation in control cells, whereas peak phosphorylation was delayed in Ado+Hcy-treated cells.
	0.80	TNF stimulation resulted in transient degradation of cytosolic IkappaB-alpha within 15 minutes, followed by the reappearance of IkappaB-alpha and a return to baseline levels within 60 minutes.
	0.70	IkappaB-alpha in cytosolic fraction and translocation of the NFkappaB subunit p65 to the nucleus in response to TNF.
	0.59	IkappaB-alpha was induced upon stimulation with TNF in control cells, but not in cells treated with Ado+Hcy (Fig. 3B).
31266502	0.98	TNF-alpha (100 ng/ml) and either IkappaBalpha inhibitor Bay11-7082 (Bay) or NF-kappaB inhibitor PDTC for 72 h. The results are shown as the means +- STD of at least three independent experiments.
	0.97	IkappaBalpha levels in MDA-MB-435-pFDR1 cells co-treated with minocycline and TNF-alpha.
	0.96	TNF-alpha-induced activation of IKK-IkappaBalpha signalling.
	0.96	TNF-alpha-induced cell fusion rate, whereas no inhibitory effect was observed for IkappaBalpha inhibition by Bay 11-7082 (Fig. 4).
	0.94	TNF-alpha binds to TNFR1, the downstream signal cascade is activated via TRAF2 recruitment and IkappaBalpha kinase complexes resulting in the release of the transcription factor NF-kappaB in M13SV1-Cre cells.
	0.91	TNF-alpha-induced IkappaBalpha phosphorylation in M13SV1-Cre cells but not in MDA-MB-435-pFDR1 cells.
	0.91	IkappaBalpha expression levels and phosphorylated IkappaBalpha levels were diminished in M13SV1-Cre cells treated with TNF-alpha and minocycline.
	0.87	IkappaBalpha and NF-kappaB expression levels were diminished in M13SV1-Cre cells co-treated with minocycline + TNF-alpha.
	0.70	TNF-alpha, minocycline and minocycline + TNF-alpha stimulation of MDA-MB-435-pFDR1 cells resulted in an increased amount of NF-kappaB p65 in the nucleus (Fig. 7a), a finding in agreement with increased phosphorylated IkappaBalpha levels that were observed in minocycline and minocycline + TNF-alpha treated MDA-MB-435-pFDR1 cells (Fig. 5b).
	0.53	TNF-alpha-induced activation of IKK-IkappaBalpha signalling
23001849	0.98	IkappaBalpha with TNF-alpha treatment (Fig. 5B), however, direct effects of Vpr on HIV-1 transcription or packaging cannot be excluded and future studies are necessary to decipher these mechanisms.
	0.97	IkappaBalpha in response to TNF-alpha stimulation.
	0.97	IkappaBalpha phosphorylation, and IkappaBalpha degradation in response to TNF-alpha (10 ng/mL) or LPS (50 ng/mL) treatment in PMA differentiated U937 cells.
	0.97	TNF-alpha (10 ng/mL) treatment on IkappaBalpha phosphorylation and IkappaBalpha degradation in U937 and U1 cells.
	0.96	IkappaBalpha in response to TNF-alpha, preliminarily suggesting that any Vpr present in these cells may actually be less able to inhibit the pathway to a significant extent, perhaps due to the presence of other HIV-1 proteins that inhibit Vpr's effects.
	0.94	IkappaBalpha levels in the presence of TNF-alpha treatment.
	0.89	IkappaBalpha phosphorylation and degradation in response to TNF-alpha (10 ng/mL) treatment in macropages (C) and PMA differentiated U937 cells.
	0.88	IkappaBalpha after twenty minutes of TNF-alpha treatment, as would be expected if NF-kappaB activation proceeded in response to TNF-alpha, while shNull/Vpr and shHSP27/Vpr cells demonstrated higher or equal levels of IkBalpha after TNF-alpha stimulation (Fig. 4C).
	0.52	IkappaBalpha with TNF-alpha treatment then control cells (Fig. 4C).
24386331	0.98	TNF-alpha induced more efficient IkappaBalpha phosphorylation at Ser32 than PMA did.
	0.98	IkappaBalpha that accompanied the protein's phosphorylation was more clearly detected in cells treated with TNF-alpha than in cells exposed to PMA.
	0.98	IkappaBalpha, measurement of in vitro IkappaBalpha phosphorylation demonstrated that TNF-alphainduced robust IKK activity in HEK293 cells and MEFs.
	0.97	TNF-alpha, PMA (10 nM) induced the phosphorylation of IKKalpha/beta (Ser176/177) and IkappaBalpha more slowly and to a lesser extent (Fig. 3A).
	0.97	TNF-alpha increased IKKalpha/beta phosphorylation at Ser176/177 by 10 min, and this was accompanied by IkappaBalpha degradation.
	0.97	IkappaBalpha phosphorylation in response to TNF-alpha, but did not cause a clear elevation of IkappaBalpha phosphorylation after PMA treatment (Fig. 3B).
	0.97	IkappaBalpha phosphorylation was not clearly detected in MEFs, we suggest that the nuclear localization of p65 induced by PMA, unlike that caused by treatment with TNF-alpha, does not result from IKK-mediated IkappaB degradation, but can be ascribed to IKKalpha/beta-mediated p65 phosphorylation.
	0.95	TNF-alpha treatment increased IKKalpha/beta (Ser176/177) and IkappaBalpha phosphorylation within 5 min and sustained IKKalpha/beta (Ser176/177) phosphorylation for 40 min.
	0.53	IkappaBalpha(1-67) in response to TNF-alpha stimulation, the IKK complex showed poor kinase activity toward its substrate after treatment with PMA (Fig. 3C).
28963466	0.98	TNFalpha- or IL-1beta-induced degradation of IkappaBalpha at 15 min or 30 min nor did it influence IkappaBalpha resynthesis at 1 and 2 h, but inhibited IkappaBalpha degradation at 6 h (Fig. 6C,D).
	0.97	TNFalpha- and IL-1beta-induced autophagy is involved in late-phase IkappaBalpha degradation and thereby maintains long-term adhesion molecules expression in endothelial cells stimulated by pro-inflammatory cytokines.
	0.97	TNFalpha- or IL-1beta-induced IkappaBalpha degradation in the presence of 3-MA or MG-132 for 6 h. These results suggest that TNFalpha- and IL-1beta-induced biphasic IkappaBalpha degradation is controlled by different degradation mechanisms; the early phase degradation is processed by the proteasome machinery while the late phase by autophagy.
	0.96	TNFalpha-induced autophagy is involved in biphasic IkappaBalpha degradation, nor is it clear whether autophagy regulates TNFalpha-induced persistent VCAM-1 and ICAM-1 expression in endothelial cells.
	0.91	IkappaBalpha blots of TNFalpha or IL-1beta control vs. 3-MA or MG-132 treatment (n = 3) at each time point were quantified by densitometry.
	0.91	IkappaBalpha was degraded rapidly and became barely detectable at 15-30 min but was resynthesized and the level was increased at 1 h and 2 h after TNFalpha treatment.
	0.87	IkappaBalpha degradation in a manner closely resembling TNFalpha except a delay in IkappaBalpha resynthesis: its level remained barely detectable at 1 h (Fig. 6B).
	0.81	TNFalpha for 6 h. IkappaBalpha, IkappaBbeta, IkappaBepsilon and Atg5 were analyzed by western blotting.
	0.73	TNFalpha- or IL-1beta-induced IkappaBalpha degradation at 15 min and 30 min as well as 6 h and also inhibited IkappaBbeta and IkappaBepsilon degradation throughout the time-course (Fig. S1).
16271147	0.98	IkappaBalpha specific bands obtained from a minimum of 4 donor pairs were used to determine fold change when compared to their respective controls and are presented as Mean (fold-change) +- S.D. [TNF-alpha (A); Pervanadate (B)].
	0.97	TNFalpha-induced degradation of IkappaBalpha in T cells
	0.97	TNFalpha, have been demonstrated to induce transcription factor NFkappaB activation by a signal-induced, proteasome-mediated degradation of the inhibitor IkappaBalpha.
	0.94	TNFa or Pervanadate), E64D appeared not to impact on the activation-induced modulation of IkappaBalpha.
	0.93	IkappaBalpha levels following stimulation with either TNFalpha or pervanadate.
	0.91	TNFa treatment in the young induced degradation of IkappaBalpha, when compared to untreated controls.
	0.84	IkappaBalpha band appears at later time-points (20 and 30 min.) in TNF activated cells from the elderly.
	0.73	TNFalpha, pretreatment with E64D failed to impact on activation-induced IkappaBalpha modification in cells pre-treated with pervanadate, irrespective of the age of the donor (fig. 4 and 5B).
19053972	0.98	IkappaBalpha-serine-32 is significantly increased after 2 minutes of TNF-alpha stimulation in MPCs isolated from both young and old animals (Figure 3A).
	0.98	IkappaBalpha protein had recovered to pre-TNF-alpha stimulation levels in MPCs isolated from both age groups (Figure 5C).
	0.96	IkappaBalpha is rapidly degraded and we demonstrate that the vast majority of IkappaBalpha has been degradated within 5 minutes of stimulation with TNF-alpha (Figure 3B).
	0.94	IkappaBalpha mRNA after stimulation with TNF-alpha as an indicator of resynthesis.
	0.86	IkappaBalpha mRNA 2 and 24 hours after stimulation with TNF-alpha, as a measure of IkappaBalpha mRNA re-synthesis, do not indicate an age-related dysfunction in this negative feedback mechanism.
	0.81	IkappaBalpha protein was almost completely degraded after TNF-alpha stimulation (Figure 3B) and needs to be replenished.
	0.54	TNF-alpha-induced IkappaBalpha mRNA expression after 2 and 24 hr stimulation with TNF-alpha in MPCs isolated from 3-mo and 32-mo.
	0.52	IkappaBalpha protein level 24 hr after TNF-alpha stimulation expressed relative to non-stimulated levels (n=2). *, significantly different from basal.
21765415	0.98	TNF (10 ng/ml), followed by immunoprecipitation and autoradiography (as in Fig. 1c); blots were probed with anti-TAX1BP1 (after immunoprecipitation with anti-TAX1BP1) or anti-beta-actin and anti-IkappaBalpha (total lysates).
	0.97	TNF or IL-1, detected in lysates after immunoprecipitation (IP) with anti-TAX1BP1 (top two blots) by immunoblot analysis with anti-HA or anti-TAX1BP1; below, immunoblot analysis of total cell lysates with anti-HA, anti-IkappaBalpha or anti-beta-actin.
	0.97	TNF or IL-1, probed with anti-Flag, anti-beta-actin plus anti-IkappaBalpha or anti-Tax.
	0.95	TNF or IL-1 (above lanes); blots were probed with anti-Flag, anti-beta-actin or anti-IkappaBalpha.
	0.91	TNF (left) or IL-1 (right); blots were probed with anti-Flag, anti-beta-actin, anti-IkappaBalpha or anti-IKKalpha.
	0.59	TNF, probed with the phosphorylation-specific antibody in i, anti-IkappaBalpha or anti-beta-actin.
	0.57	TNF, probed with antibody specific for TAX1BP1 phosphorylated at Ser593, anti-TAX1BP1, anti-beta-actin plus anti-IkappaBalpha or anti-Tax.
23573150	0.98	TNF-alpha and LPS can activate the canonical NF-kappaB pathway; then the transcriptional factor NF-kappaB is released to the nuclear after the phosphorylation, ubiquitination, and proteolytic degradation of IkappaBalpha.
	0.98	TNF-alpha-induced IkappaBalpha degradation in a dose-dependent manner (Figure 2(a), lower panel).
	0.97	TNF-alpha-induced IkappaBalpha degradation, we examined the proteolytic degradation of IkappaBalpha in the presence of TNF-alpha from 0 to 60 min.
	0.97	TNF-alpha stimulation on HepG2 cells is optimal for inducing IkappaBalpha degradation.
	0.93	TNF-alpha has been evident of suppressing cancerous carcinoma, it also stimulates activation of NF-kappaB signaling via degradation of IkappaBalpha, leading to apoptosis resistance, as well as TNF-alpha resistance in cancer cells.
	0.92	TNF-alpha-induced degradation of IkappaBalpha.
24146961	0.98	TNFalpha-dependent IkappaBalpha Phosphorylation and Degradation
	0.97	TNFalpha-induced IkappaBalpha phosphorylation which is another condition for NF-kappaB translocation.
	0.95	TNFalpha-induced NF-kappaB activation by digitoflavone was due to inhibition of IkappaBalpha degradation.
	0.92	IkappaBalpha, digitoflavone completely suppressed TNFalpha-induced IkappaBalpha phosphorylation (Fig. 4A).
	0.90	TNFalpha for different times, and then tested for phosphorylated IKKalpha/beta and IkappaBalpha in cytosolic fractions by Western blotting analysis.
	0.72	TNFalpha-induced phosphorylation of IKKalpha/beta and IkappaBalpha.
28900035	0.98	IkappaBalpha after TNFalpha treatment.
	0.97	IkappaBalpha (ser32), and p-JNK were detected in M2 cells after stimulation with TNFalpha compared with M2-PrP-/- cells.
	0.97	IkappaBalpha was detected at 10 min after TNFalpha treatment and persisted for at least 40 min in the M2 wild-type cells (Fig. 1C).
	0.97	TNFalpha treatment barely altered the levels of either p-IkappaBalpha or total IkappaBalpha (Fig. 1C).
	0.90	TNFalpha up-regulates the expression of p-IkappaB-kinase alpha/beta (p-IKKalpha/beta), p-p65, and p-JNK, but down-regulates the IkappaBalpha protein, all of which are downstream signaling intermediates in the TNF receptor signaling cascade.
	0.54	TNFalpha (10 ng/ml) induced robust IkappaBalpha degradation via the proteasomal pathway in A7 cells, it had no effect on M2 cells that do not express FLNa.
21912593	0.98	TNF-alpha showed significantly enhanced IkappaBalpha phosphorylation and decreased amounts of IkappaBalpha relative to complemented FANCD2 cells (FA-D2/D2) (Fig. 2A).
	0.97	TNF-alphainduced transient loss and subsequent resynthesis of IkappaBalpha protein in FANCD2-deficient (FA-D2/vec) and FANCD2-proficient cells (FA-D2/D2) (Fig. 2B).
	0.97	TNF-alpha exposure, the amount of IkappaBalpha protein was lower and the reduction was prolonged in FANCD2-deficient cells relative to FANCD2-proficient cells (Fig. 2B).
	0.96	TNF-alpha induced NF-kappaB activity in FA cells, using IkappaBalpha levels as a marker.
	0.93	TNF-alpha(100 ng/ml), and cell lysates were examined by immunoblotting (IB) using anti-phospho (P) Ser 32/36 IkappaBalpha or anti-alpha-tubulin.
23071583	0.98	TNF-alpha-induced IkappaBalpha degradation and p65/RelA phosphorylation regulate NF-kappaB activation.
	0.97	TNF-alpha-induced IkappaBalpha degradation by inhibiting the IKK-beta activation
	0.96	TNFalpha for 30 mins and total cell extracts were processed for western blot analysis using antibodies against IkappaBalpha, phosphoIkappaBalpha and alpha-tubulin.
	0.94	TNF-alpha-induced phosphorylation [Figures 4B and 4C panel (ii)] and degradation [Figures 4A and 4C panel (i)] of IkappaBalpha.
	0.92	TNF-alpha-induced IkappaBalpha degradation by inhibiting the activation of IKK-beta.
28829844	0.98	IkappaBalpha significantly reduced TNFalpha-associated IL-1beta induction by 72% (Fig. 6D, P < 0.05).
	0.97	IkappaBalpha with TMP prevented IL-1alpha-, A2E-, LPS-, and TNFalpha-induced NFkappaB-mediated upregulation and release of the proinflammatory cytokines IL-1beta and IL-6 from ARPE-19 cells (by as much as 93%).
	0.97	TNFalpha (0.25-25 ng/mL, Fig. 6B, P < 0.05, P < 0.01) caused significant increases in the secretion of GLuc, indicating activation of NFkappaB. Next, we assessed whether our DHFR-IkappaBalpha strategy was broadly applicable for dampening NFkappaB signaling triggered by these stimuli.
	0.97	IkappaBalpha fusion protein with dox/TMP, cells are protected from the proinflammatory effects of IL-1alpha, TNFalpha, and LPS, reducing NFkappaB-dependent gene expression and cytokine production by approximately 80% to 90%.
	0.65	IkappaBalpha also prevents LPS and TNFalpha-mediated NFkappaB priming.
29207489	0.98	TNF-alpha-induced IkappaBalpha degradation, Ser-536 phosphorylation, or the nuclear translocation of p65 in A549 cells.
	0.97	TNF-alpha-induced IkappaBalpha phosphorylation and subsequent degradation.
	0.97	IkappaBalpha phosphorylation was initiated within 5 min of TNF-alpha stimulation, and its subsequent degradation occurred within 15 min, in A549 cells.
	0.81	TNF-alpha-induced IkappaBalpha degradation.
	0.80	IkappaBalpha and only slightly decreased TNF-alpha-induced IkappaBalpha degradation at 50 microM (Figure 5).
16191192	0.98	IkappaBalpha Mut cells were plated in parallel cultures in the absence or presence of Dox (2 mug/ml), and each group stimulated tonically with TNFalpha to induce NF-kappaB activation in the oscillatory mode.
	0.96	TNFalpha are observed with other NF-kappaB activating stimuli, we stimulated HeLatTA/FLAG-IkappaBalpha Mut with IL-1alpha.
	0.94	TNF stimulation rapidly activates IKK briefly over 5-15 min, after which the kinase inactivates, thereby allowing newly resynthesized IkappaBalpha to recapture activated NF-kappaB and return it to its inactivated cytoplasmic form.
	0.67	TNFalpha-stimulated in HeLatTA/FLAG-IkappaBalpha Mut cells cultured in the absence or presence of Dox.
31540489	0.98	TNF-alpha-induced IkB-alpha degradation (c) by western blot analysis.
	0.95	TNF-alpha-Induced MAPK, Akt, and IkappaB-alpha Signaling Pathways
	0.92	TNF-alpha can induce the degradation of IkappaB-alpha and the translocation of NF-kappaB activity.
	0.91	TNF-alpha-activated MAPKs, Akt, and IkappaB-alpha signaling pathways have been involved in tumor progression via AP-1 or NF-kappaB transcriptional activities.
24530305	0.98	NFKBIA (which respectively encode IL-8, A20 and IkappaBalpha), three NF-kappaB-dependent genes strongly expressed 1 hr after exposure to TNF.
	0.92	TNF and other inducers of the canonical NF-kappaB pathway promote phosphorylation and degradation of IkappaBalpha, releasing RelA-p50 and exposing its nuclear localization sequence (NLS).
	0.86	TNF-treated cells) encode cytokines (e.g. IL-8 and IL-6) as well as regulators of the NF-kappaB pathway itself (e.g. A20 and IkappaBalpha).
24587316	0.98	TNF-alpha on IkappaBalpha phosphorylation.
	0.95	TNF-alpha for 5-15 min resulted in phosphorylation (Fig. 4) and disappearance of IkappaBalpha (Fig. 5A).
	0.92	IkappaBalpha phosphorylation (Fig. 4) and reversed the inhibitory effect of TNF-alpha on eosinophil apoptosis (Fig. 6C).
29853786	0.98	TNF-alpha significantly reduced IkappaBalpha at early time points, which then appeared to peak at 2 h and decrease at 24 h (significant for TNF-alpha only).
	0.94	TNF-alpha, IkappaBalpha was significantly downregulated early (30 minutes).
	0.82	IkappaBalpha releases the transcription-activating subunits of NF-kappaB. The classic pathway of NF-kappaB activation is triggered by the IL-1 receptor (IL-1R), the TNF receptor (TNFR), and pattern recognition receptors (PRRs), through downstream activation of IKKbeta and IkappaBalpha and release of p65-p50.
18948845	0.98	TNF-alpha provokes a marked increase in whole cell levels of phosphorylated IkappaBalpha (Ser32) at 5 min that then degrades by 10 min.
	0.97	IkappaBalpha phosphorylation, HTS does not alter the relative amount of TNF-alpha-induced p38 phosphorylation.
21279667	0.98	TNF-alpha, IkappaBalpha protein levels were nearly restored in cells that express p65 (lane 7), and this was blocked in cells that lacked p65 protein (lane 8).
	0.93	IkappaBalpha increased apoptosis in response to TNF-alpha and chemotherapeutic agents.
24324544	0.98	IkappaBalpha, A20, intracellular TNFalpha.
	0.97	TNFalpha stimulation, A20-deficient cells do not exhibit limit cycle oscillation, but reach the active steady state, characterized by a high IKK activity, a high level of nuclear NF-kappaB and correspondingly high level of IkappaBalpha transcript, but low level of IkappaBalpha protein, which is constantly degraded due to the high IKK activity.
19874889	0.97	IkappaBalpha stability to negatively regulate TNFalpha induced NF-kappaB activation.
	0.97	IkappaBalpha can be deubiquitinated by its associated USP11 in collaboration with USP15 to prevent excessive NF-kappaB activation induced by TNFalpha.
	0.95	IkappaBalpha ubiquitination and deubiquitination processes function as a Yin-Yang regulatory mechanism on TNFalpha-induced NF-kappaB activation.
	0.94	IkappaBalpha and attenuates IkappaBalpha degradation to negatively regulate TNFalpha-induced NF-kappaB activation.
	0.94	IkappaBalpha at the early phase and USP15 fits in at a later time point in the TNFalpha-induced NF-kappaB activation.
	0.94	TNFalpha-induced IkappaBalpha ubiquitination level in the cells.
	0.93	TNFalpha-mediated NF-kappaB activation through modulating IkappaBalpha stability.
	0.93	IkappaBalpha in the transfected HEK 293T cells or endogenous IkappaBalpha in HeLa cells after TNFalpha treatment in the presence of MG132 were immunoprecipitated from cell lysates with anti-Flag or anti-IkappaBalpha antibodies, and then incubated with recombinant His-USP11-WT or -C318A mutant.
	0.93	TNFalpha-induced NF-kappaB activation by modulating IkappaBalpha ubiquitination and turnover in the cells.
	0.92	TNFalpha induced a stronger IkappaBalpha ubiquitination and a stronger NF-kappaB nuclear translocation in two USP11 knockdown cell lines compared to the control cells whereas TNFalpha induced a similar level of IKK, JNK and ERK phosphorylation.
	0.92	TNFalpha-induced TAK1-IKK activation, IkappaBalpha is phosphorylated by IKKbeta and subsequently ubiquitinated for degradation.
	0.89	IkappaBalpha deubiquitination in the negative regulation of the TNFalpha-induced NF-kappaB activation has not been completely defined.
	0.89	IkappaBalpha associated deubiquitinase and further characterize the mechanism and role of IkappaBalpha deubiquitination in the attenuation of TNFalpha-induced NF-kappaB activation.
	0.86	TNFalpha-induced IkappaBalpha ubiquitination (Fig. S1A) as well as TNFalpha- and IKKbeta-induced NF-kappaB activation (Figs. S1B and C).
	0.84	IkappaBalpha deubiquitination through a TNFalpha-induced interaction with IkappaBalpha in the CSN complex.
	0.79	IkappaBalpha to inhibit the TNFalpha-induced NF-kappaB activation through an inducible interaction of the CSN with IkappaBalpha.
	0.79	IkappaBalpha protein level is essential for preventing excessive TNFalpha-mediated cellular responses.
	0.78	TNFalpha-mediated IkappaBalpha ubiquitination and NF-kappaB activation but had no effect on TNFalpha-mediated MAPK activation.
	0.66	TNFalpha-induced IkappaBalpha ubiquitination and NF-kappaB activation.
	0.58	TNFalpha-induced IkappaBalpha ubiquitination and NF-kappaB activation
	0.54	TNFalpha-induced IkappaBalpha ubiquitination and NF-kappaB activation.
31909200	0.97	IkappaBalpha degradation and phosphorylation in response to both cytokines, IL-1beta stimulated a higher fold change in IkappaBalpha phosphorylation that reached a maximum slightly faster than TNFalpha in MCF-7 cells.
	0.97	IkappaBalpha results, phosphorylation of p65 on serine 536 was increased after TNFalpha treatment and the increased phosphorylation signal was inhibited by IKK16 treatment (Fig. 5a).
	0.96	IkappaBalpha phosphorylation was detected as early as 4 min and the phosphorylation signal started decreasing after 10 min of TNFalpha treatment (Fig. 4a).
	0.95	IkappaBalpha protein were detected starting around 10 min after TNFalpha treatment confirming the decreased phosphorylation signal is due to degradation of total IkappaBalpha (Fig. 4a).
	0.93	IkappaBalpha in response to TNFalpha treatment could be observed with this assay using as low as 3500 cells with a linear range of detection between 3500 and 60,000 cells per well (Fig. 2c, d).
	0.93	IkappaBalpha in response to TNFalpha treatment at various and early time points.
	0.93	IkappaBalpha is a result of de novo transcription/translation of IkappaBalpha gene, the MCF-7 cells were treated with TNFalpha in the presence of cycloheximide for the same extended time to block protein synthesis and total IkappaBalpha was measured.
	0.93	IkappaBalpha degradation in MCF-7 cells treated with TNFalpha was inhibited by IKK16 in a dose-dependent fashion with an IC50 of 1.44 microM, which is similar to what was previously reported.
	0.92	TNFalpha (50 ng per ml, 30 min) before total IkappaBalpha was measured by NanoBiT cell-based immunoassays.
	0.89	IkappaBalpha phosphorylation signal after 10 min of TNFalpha treatment may be due to immediate degradation of the phosphorylated IkappaBalpha.
	0.89	TNFalpha treatment caused maximal IkappaBalpha degradation by 30 min and then extended the time course to 2 h of TNFalpha treatment to see if newly synthesized IkappaBalpha appears.
	0.88	IkappaBalpha on serine 32 was increased after TNFalpha treatment and this phosphorylation was suppressed by IKK16, an IKK complex selective inhibitor (Fig. 3a).
	0.88	IkappaBalpha protein also decreased due to its degradation after TNFalpha treatment and this reduction was abolished with IKK16 treatment (Fig. 3b).
	0.87	TNFalpha induced degradation of IkappaBalpha by the IKK complex inhibitor IKK16 and generated the corresponding IC50 value.
	0.83	TNFalpha (10 ng per ml, 30 min) before IkappaBalpha phosphorylation was measured by NanoBiT cell-based immunoassay as described in Material and Methods section.
	0.81	IkappaBalpha plus and minus TNFalpha treatment.
	0.78	TNFalpha for 30 min, before total IkappaBalpha level was measured.
	0.69	IkappaBalpha was measured in various numbers of MCF-7 cells after TNFalpha treatment.
	0.67	TNFalpha treatment, the phospho-IkappaBalpha signal increased with increasing cell number in a linear fashion (Fig. 2c).
	0.55	IkappaBalpha level to assess its TNFalpha-mediated degradation.
27212040	0.97	TNF-alpha-induced IkappaBalpha degradation at 10 and 15 min was significantly abolished by honokiol treatment (3 muM) (Fig. 4A,B).
	0.96	TNF-alpha stimulation, the inhibitor of NF-kappaB alpha (IkappaBalpha) is phosphorylated and sequentially conjugated with K48-linked polyubiquitin, which leads to degradation of IkappaBalpha by the 26S proteasome.
	0.96	TNF-alpha-induced IkappaBalpha degradation in ECs.
	0.93	TNF-alpha-induced neutrophil adhesion on cerebral ECs by disrupting the polyubiquitination and degradation of IkappaBalpha to block NF-kappaB-controlled VCAM-1 expression.
	0.92	TNF-alpha-induced IkappaBalpha degradation in ECs.
	0.91	TNF-alpha-induced Lys48-linked polyubiquitination, including IkappaBalpha-polyubiquitin interaction.
	0.89	IkappaBalpha (Red) and p65 (green) in ECs preincubated with DMSO or honokiol (3 muM) for 30 min, then with TNF-alpha (10 ng/ml) for 15 min.
	0.88	IkappaBalpha induced by TNF-alpha on immunoprecipitation assay (Fig. 6B).
	0.87	TNF-alpha-induced neutrophil adhesion and VCAM-1 gene expression in cerebral ECs, at least in part by directly inhibiting ubiquitination-mediated IkappaBalpha degradation and then preventing NF-kappaB nuclear translocation.
	0.87	TNF-alpha-induced IkappaBalpha degradation and the GABAA receptor antagonist, SR95531, also did not affect the inhibitory effect of honokiol on TNF-alpha-induced IkappaBalpha degradation in ECs, suggesting that honokiol-blocked IkappaBalpha degradation is not changed by the GABAA receptor antagonist as well as GABAA agonist, although muscimol and SR95531 does not address the benzodiazepine binding site of the GABAA receptor.
	0.87	TNF-alpha-induced IkappaBalpha proteosomal degradation.
	0.86	TNF-alpha still caused the IkappaBalpha degradation in the presence of honokiol after longer 30 min stimulation in Fig. 4A, suggesting that the effect of honokiol on TNF-alpha-mediated NF-kappaB activation may be a delayed response rather than a merely suppressed response, although honokiol would repress the VCAM-1 expression or neutrophil adhesion after 1-3 h TNF-alpha stimulation (Figs 1 and 2).
	0.83	TNF-alpha-induced IkappaBalpha phosphorylation was accumulated by honokiol treatment (Fig. 4A,B), suggesting that honokiol may mainly alter on the IkappaBalpha stability instead of phosphorylation.
	0.75	IkappaBalpha, suggesting that honokiol may not totally control the TNF-alpha-regulated NF-kappaB activity because of IkappaBalpha-independent regulation.
	0.57	IkappaBalpha, phospho-IkappaBalphaand tubulin (loading control) protein expression in ECs pre-treated with DMSO or honokiol (3 muM) for 30 min, then stimulated with TNF-alpha (10 ng/ml) at different times (5, 10, 15, and 30 min).
	0.52	IkappaBalpha induced by TNF-alpha (Fig. 6C).
27381163	0.97	IkappaBalpha and NF-kappaB oscillations in response to continuous TNFalpha.
	0.97	IkappaBalpha and serine 536-phosphorylated NF-kappaB p65 levels in WT cells stimulated with two pulses of TNFalpha, or alternate TNFalpha and IL-1beta pulses at 60 min interval.
	0.94	IkappaBalpha-eGFP p65-mCherry C9L cells pulsed at 100 min interval (see Fig. 2h for single-cell traces, Fig. 2i for fraction of responding cells), the average amplitude of p65-mCherry nuclear translocation was similar to that of cells stimulated with continuous TNFalpha (80% of the first-peak amplitude, Fig. 2j).
	0.93	IkappaBalpha, IkappaBe and A20) and a number of pro-inflammatory signalling molecules including cytokines and chemokines (IL8, CSF2, CCL2, CCL5, CXCL1, CXCL2, LIF, TNFalpha, TNFAIP6 and IL-1beta).
	0.90	TNFalpha (or IL-1beta) led to a rapid and synchronous degradation of IkappaBalpha-eGFP, which coincided with a nuclear p65-mCherry translocation (Fig. 1b-d, see Supplementary Table 1 for the number of cells analysed in specific experiments).
	0.88	IkappaBalpha-eGFP intensities shown) respond to the first (depicted at 10 min after stimulation), as well as to the second TNFalpha pulse (at 80 min after start of the experiment).
	0.87	TNFalpha based on the IkappaBalpha-eGFP trajectories (for times >35 min, Fig. 5).
	0.79	IkappaBalpha levels oscillate out-of-phase with NF-kappaB p65 nuclear localization in response to TNFalpha and IL-1beta stimulation.
	0.72	IkappaBalpha negative feedback, whilst the IKK module depicted the transduction pathway downstream of TNFalpha and IL-1beta.
	0.60	TNFalpha and IL-1beta pulses applied at 0 and 60 min Shown is the mean (+-s.d.) of normalized total IkappaBalpha-GFP intensity in single C9 cells.
	0.58	TNFalpha pulses (as defined by amplitude of NF-kappaB translocation) was controlled by parameters associated with the IKKK and A20 signalling (for example, A20 mRNA transcription, protein translation rates and half-lives, c1, c2, c3, c4; IKKK level, IKKKtott; A20-induced IKKK inhibition, kA20; half-maximal IKK activation, sIKKK, Fig. 4g shown in blue), but not the core NF-kappaB-IkappaBalpha or receptor signalling (see also Supplementary Fig. 28).
	0.57	IkappaBalpha, IkappaBe, Rel, RelB, NF-kappaB1 and NF-kappaB2) and cytokine response genes (CXCL2, CXCL1, IL8, TNFAIP6, CSF2, TNFalpha, LIF, IL-1beta and CCL2).
	0.53	IkappaBalpha-GFP response to the first TNFalpha pulse.
	0.51	IkappaBalpha-eGFP degradation) in response to pulsatile cytokine stimulation, with fewer cells responding at shorter TNFalpha pulsing intervals.
23850221	0.97	TNFalpha released chromatin-bound IkappaBalpha in keratinocytes, as we previously found in fibroblasts.
	0.97	IkappaBalpha targets (n = 12) were robustly induced by TNFalpha treatment (up to 12-fold) following different kinetics (Figures 3F) and to a lesser extent (up to 3-fold) by Ca2+ treatment (Figure S3B) or IkappaBalpha KD (Figure S3C).
	0.97	IkappaBalpha after 20 min of TNFalpha or 48 hr Ca2+ treatments.
	0.96	IkappaBalpha target genes following TNFalpha treatment analyzed by qRT-PCR.
	0.94	IkappaBalpha targets by TNFalpha, we attempted to use different mutant MEFs, including the p65, Ikkalpha, Ikkbeta, and the triple p65;p50;c-Rel KO.
	0.94	TNFalpha treatment result in the loss of chromatin-associated IkappaBalpha and Polycomb release, associated with a moderate or temporary activation of Hox and Irx transcription, respectively.
	0.92	IkappaBalpha involves its desumoylation and subsequent ubiquitylation, and which modifications in both IkappaBalpha and histones are imposed by TNFalpha and induce PS-IkappaBalpha release from the chromatin, is currently under investigation.
	0.91	IkappaBalpha KO cells failed to activate Hox transcription in response to TNFalpha (Figure 4G), which is consistent with a defective release of PRC2 proteins (Figure 4F).
	0.90	IkappaBalpha modulates Polycomb recruitment and imparts their competence to be activated by TNFalpha.
	0.90	TNFalpha treatment induced the dissociation of SUZ12 from IkappaBalpha target regions, but not non-IkappaBalpha targets (Figure 4C).
	0.88	IkappaBalpha associates with the promoter of Notch target genes correlating with their transcriptional repression, which is reverted by TNFalpha.
	0.50	IkappaBalpha in WT and IkappaBalpha KO MEFs treated with TNFalpha.
16177180	0.97	IkappaBalpha, or HUVEC were stimulated with TNF-alpha for the indicated intervals, total RNA was analyzed by RT-PCR.
	0.93	IkappaBalpha HMEC-1 when stimulated with TNF-alpha compared to stimulated control cells.
	0.93	IkappaBalpha largely abolished TNF-alpha-induced expression of the investigated genes in HMEC-1 cells.
	0.93	TNF-alpha induction of this gene was comparable to the extent observed by the previous authors, but at the same time TD-IkappaBalpha was able to completely suppress this induction.
	0.89	TNF-alpha-induced genes in control HMEC-1 were repressed in TD-IkappaBalpha transducing cells (94%), while the 76% of them were already up-regulated in CA-IKK2 infected cells in the absence of stimulation.
	0.85	IkappaBalpha and stimulated by TNF-alpha at different time intervals (data not shown), suggesting an absolute dependence on the IKK/NF-kappaB module.
	0.83	TNF-alpha, repressed by TD-IkappaBalpha but not up-regulated by CA-IKK2 is of particular interest.
	0.78	IkappaBalpha, CA IKK2 or empty vector were cultured to ~80% confluence, stimulated with of TNF-alpha for 16 h and RNA expression profiles were determined by oligonucleotide array hybridization in three independent experiments.
	0.74	IkappaBalpha were stimulated with TNF-alpha for the time intervals indicated.
	0.73	TNF-alpha-regulated genes on NF-kappaB. A constitutively active IKK2 was sufficient for maximal induction of most target genes, whereas a transdominant IkappaBalpha suppressed gene expression.
17565690	0.97	IkappaBalpha mutant LN-18 cells treated with TNF-alpha for 3 hr.
	0.97	TNF-alpha on pp53 and p21 was studied in LN-229 cells transfected with IkappaBalpha dominant negative construct.
	0.97	IkappaBalpha dominant negative construct and the expression of nuclear p65 was determined after exposure to TNF-alpha for 6 hr.
	0.97	TNF-alpha mediated cytotoxicity, we used a stable IkappaBalpha mutant LN-18 cell line that was rendered sensitive to TNF-alpha induced death by transfection with a double mutant construct pcDNA3-IkappaBalpha in which both serines (32 and 36) at the amino-terminal are replaced with alanine that are essential for phosphorylation of IkappaBalpha during NF-kappaB activation.
	0.97	IkappaBalpha dominant negative construct transfected LN-229 cells exposed to TNF-alpha suggested that p53 might not be downstream of NF-kappaB and p21 could be regulated independently by the p53.
	0.93	TNF-alpha in LN-18 cells, we examined the role of NF-kappaB pathway in the regulation of p21 using a stable IkappaBalpha mutant LN-18 cell line.
	0.84	IkappaBalpha mutant cell line to TNF-alpha determined by MTT assay and PARP cleavage.
	0.75	IkappaBalpha mutant LN-18 cells were treated with TNF-alpha (10 ng/ml) for different time points and cleavage of PARP (89 kD fragment) was determined by Western blotting.
	0.74	IkappaBalpha mutant LN-18 cells and was not induced on stimulation with TNF-alpha (Fig. 3C, and 3D) suggesting that p21 expression might be regulated by the NF-kappaB pathway.
	0.62	TNF-alpha on cell viability and expression of p21 and p27 in IkappaBalpha mutant LN-18 cells.
20354190	0.97	TNF induced IkappaBalpha phosphorylation in control cells within 5 min, but noscapine-pretreated cells inhibited the phosphorylation of IkappaBalpha.
	0.92	TNF-dependent IkappaBalpha phosphorylation and degradation
	0.92	TNF induced IkappaBalpha degradation in control cells within 5 min, reaching maximum degradation at 15-30 min, but TNF could not induce IkappaBalpha degradation in noscapine-pretreated cells (Figure 5B, left-top panel).
	0.83	TNF-induced NF-kappaB activation by noscapine is caused by inhibition of IkappaBalpha degradation, we pretreated cells with noscapine and then exposed them to TNF for various time periods.
	0.82	IkappaBalpha, we tested the effect of noscapine on TNF-induced IKK activation.
	0.82	IkappaBalpha by TNF.
	0.78	IkappaBalpha showed that TNF induced IkappaBalpha phosphorylation, whereas noscapine suppressed it (Figure 5B, right).
	0.77	TNF-induced IkappaBalpha phosphorylation needed for IkappaBalpha degradation.
	0.77	TNF-dependent IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, and p65 nuclear translocation
	0.70	TNF-induced IkappaBalpha kinase activity.
18974130	0.97	TNF induced degradation of IkappaBalpha as quickly as 10 min, and resynthesis occurred at 60 min (Fig. 2B).
	0.97	TNF induced phosphorylation of IkappaBalpha and that picroliv suppressed it (Fig. 2D).
	0.96	IkappaBalpha, we studied its effects on TNF-induced activation of IKK by immune complex kinase assays.
	0.90	TNF-induced activation of NF-kappaB is mediated through sequential interaction of TNFR with TRADD, TRAF2, TAK1, and IKK, resulting in phosphorylation of IkappaBalpha.
	0.89	TNF-induced phosphorylation of IkappaBalpha is mediated through the activation of IkappaBalpha kinase (IKK).
	0.87	TNF induced phosphorylation of IkappaBa within 5 min (Fig. 2C); and picroliv treatment inhibited this phosphorylation.
	0.80	TNF-induced phosphorylation of IkappaBalpha thereby preventing its degradation.
	0.78	IkappaBalpha by TNF in the presence of ALLN.
	0.62	TNF-induced degradation of IkappaBalpha.
23593410	0.97	IkappaB-alpha degradation is required for nuclear translocation of p65, we sought to determine whether PMS1077 could also suppress the TNF-alpha induced nuclear translocation of p65.
	0.95	TNF-alpha dependent IkappaB-alpha phosphorylation and degradation
	0.95	TNF-alpha induced activation of NF-kappaB via suppressing phosphorylation and degradation of IkappaB-alpha.
	0.92	IkappaB-alpha in HEK293T, we found that TNF-alpha induced IkappaB-alpha degradation reached the maximum at 0.5 h to 1 h and that resynthesis of IkappaB-alpha occurred 2 h to 4 h after TNF-alpha treatment (Fig. 4A).
	0.90	TNF-alpha (20 ng/ml) for the indicated periods of time; (B) PMS1077 inhibited TNF-alpha induced IkappaB-alpha degradation.
	0.90	TNF-alpha (20 ng/ml) for 0.5 h; (C) PMS1077 inhibited TNF-alpha induced IkappaB-alpha phosphorylation.
	0.89	TNF-alpha induced IkappaB-alpha degradation, which leads to suppression of NF-kappaB activation.
	0.87	TNF-alpha induced IkappaB-alpha degradation, IkappaB-alpha phosphorylation, p65 phosphorylation.
	0.78	TNF-alpha induced IkappaB-alpha degradation, IkappaB-alpha phosphorylation.
24864134	0.97	IkappaB-alpha, and Phosphorylated-IkappaB-alpha in HT-29 Cells Treated with TNF-alpha and/or 2-Cl-IB-MECA
	0.97	IkappaB-alpha expression and the increased expression of phosphorylated-IkappaB-alpha in the cytoplasm, induced by TNF-alpha, could be observed in Figures 2(c)2 and 2(d)2.
	0.97	TNF-alpha attenuated NF-kappaB p65 nuclear translocation, as p65 protein decreased in the nucleus of cells and increased in the cytoplasm, inhibited the degradation of IkappaB-alpha and reduced phosphorylated-IkappaB-alpha level, compared to TNF-alpha-only-treated groups (P < 0.05, Figures 4 and 5).
	0.95	IkappaB-alpha to increase in the cytoplasm of TNF-alpha-treated cells.
	0.93	TNF-alpha-induced NF-kappaB activation, we estimated the level of NF-kappaB p65, IkappaB-alpha, and phosphorylated-IkappaB-alpha using western blot after HT29 cells were treated with various concentrations (10 nM, 30 nM, and 50 nM) of 2-Cl-IB-MECA for 30 min and then incubated with TNF-alpha (10 ng/mL) for 30 min.
	0.92	TNF-alpha-induced decrease in IkappaB-alpha and inhibited phosphorylation of IkappaB-alpha, leading to failed nuclear translocation of NF-kappaB p65 in HT-29 cells in a concentration-dependent manner.
	0.84	TNF-alpha, IkappaB-alpha is first phosphorylated and rapidly degraded in the proteasomes, allowing NF-kappaB nuclear translocation and gene activation.
	0.80	TNF-alpha resulted in a reduction in IkappaB-alpha expression and an increase in p-IkappaB-alpha expression in HT-29 cells.
	0.68	TNF-alpha attenuated NF-kappaB p65 nuclear translocation as p65 protein decreased in the nucleus of cells and increased in the cytoplasm, inhibited the degradation of IkappaB-alpha, and reduced phosphorylated-IkappaB-alpha level significantly, compared to TNF-alpha-only-treated groups.
24957606	0.97	IkappaBalpha degradation after 0.25 h; however, a rapid disappearance was observed 0.5 h after TNF treatment followed by IkappaBalpha resynthesis within 1 h. By contrast, in the ATM-depleted cells IkappaBalpha degradation was significantly delayed, not being apparent until after 1 h of TNF treatment (Figure 2B).
	0.97	IkappaBalpha and a delay in TNF-induced IkappaBalpha degradation (Figure 2B and D).
	0.95	TNF-induced IkappaBalpha degradation.
	0.95	TNFalpha activates the IKK complex, a rate-limiting kinase responsible for IkappaBalpha phosphorylation at Ser residues 32 and 36 in its NH2 terminal regulatory domain.
	0.95	TNF exposure regulates expression of a subset of genes by controlling two key steps in the pathway: (i) facilitating optimal IkappaBalpha degradation by forming a viable IkappaBalpha-beta-TrCP-ubiquitin ligase complex and (ii) RelA Ser 276 phosphorylation by promoting R6K/PKAc association with RelA.
	0.92	TNF-induced IkappaBalpha degradation was measured in CEs using western immunoblot.
	0.87	IkappaBalpha after TNF exposure.
	0.80	TNF response pathway, ATM seems to directly work at the level of E3 ubiquitin ligase recruitment to facilitate IkappaBalpha degradation.
	0.68	TNF to the TNF receptor on the plasma membrane activates two parallel pathways: (1) IKK complex activation resulting in IkappaBalpha phosphorylation and (2) ROS generation leading to DNA double-strand breaks.
25479425	0.97	I-kappaBalpha is inhibited at 10 minutes in cells stimulated with TNFalpha or IL-1beta (10 ng/ml) by either 400 mOsm HTS or SOR treatment.
	0.96	I-kappaBalpha induced by both TNFalpha and IL-1beta.
	0.95	TNFalpha signaling requires IKKbeta associated with NEMO, IL-1beta signaling is more diverse and can utilize either IKKalpha or IKKbeta (bound to NEMO) resulting in phosphorylation and degradation of I-kappaBalpha, which activates NF-kappaB. Consequently, these stimuli were chosen to contrast and classify potential mechanistic targets of HOsm treatment during receptor-stimulated inflammation in an alveolar pneumocyte line (A549).
	0.93	TNFalpha stimulated A549 cells, HOsm media inhibited I-kappaBalpha phosphorylation, NF-kappaB translocation into the nucleus and NF-kappaB nuclear binding.
	0.92	I-kappaBalpha phosphorylation was noted at 10 minutes following stimulation with either TNFalpha or IL-1beta (p<0.05) [Figure 5B&C].
	0.92	I-kappaBalpha phosphorylation similarly with either TNFalpha or IL-1beta stimulation at the early time points but appears to only delay peak phosphorylation.
	0.90	TNFalpha or IL-1beta stimulation, I-kappaBalpha phosphorylation in the setting of HOsm treatment peaked at 30 minutes at or above the levels seen in isotonic media at the same time point.
	0.86	I-kappaBalpha degradation and p65 translocation when TNFalpha is stimulus, but not with IL-1beta.
	0.84	TNFalpha requires both IKKalpha and IKKbeta for I-kappaBalpha phosphorylation.
28656529	0.97	TNF-alpha-induced CXCL8 secretion was then determined to require the p38 MAPK, but not STAT1/3, PI3K, Akt, JNK, ERK or IkBalpha.
	0.97	TNF-alpha-induced IkBalpha phosphorylation and degradation.
	0.97	TNF-alpha and/or IL-22 as in Fig. 3 before preparing cell extracts for SDS-PAGE and Western blotting for phosphorylated and total IkBalpha and actin.
	0.96	TNF-alpha to TNFR1 leads to the intracellular recruitment of MAPK pathway signal transducers, inducing the c-Jun N-terminal kinases (JNK), p38 MAPK, and ERK1/2 kinases, as well as signaling transducers in the IKK/IkBalpha/NFkB signaling pathway.
	0.96	TNF-alpha-induced IkBalpha phosphorylation and degradation.
	0.95	TNF-alpha or IL-22 and TNF-alpha resulted in a significant degradation of total IkBalpha levels at 30 minutes (Figs. 4A and C).
	0.94	IkBalpha in colonic subepithelial myofibroblasts, IL-22 had no enhancing effect on IkBalpha phosphorylation or degradation with TNF-alpha stimulation of the HT-29 cells.
	0.70	TNF-alpha resulted in a significant suppression of IkBalpha phosphorylation at 30 minutes, yet this suppression was still significantly elevated compared to the untreated controls.
	0.56	TNF-alpha-induced CXCL8 secretion levels were enhanced with IL-22 co-stimulation, this suppressive effect of IL-22 on IkBalpha phosphorylation was apparently not important and may have been reflective of a delay in IkBalpha phosphorylation.
20460401	0.97	TNF-induced IkappaBalpha degradation started at 5 min after TNF treatment and reached maximum level at 10 min.
	0.97	TNF-induced IkappaBalpha degradation, which in turn leads to suppression of the activation of NF-kappaB.
	0.97	IkappaBalpha induced by TNF.
	0.95	TNF induced IkappaBalpha phosphorylation at serine 32 and that sesamin suppressed this phosphorylation (Fig. 4C).
	0.94	TNF-induced activation of the enzyme IKK which triggers the phosphorylation of IkappaBalpha.
	0.90	TNF-induced degradation of IkappaBalpha was caused by inhibition of phosphorylation of IkappaBalpha.
	0.67	TNF-induced degradation of IkappaBalpha.
24083678	0.97	TNFalpha caused a gradual decrease in overall IkappaBalpha protein abundance, which reached its lowest point 40 minutes after stimulation and returned to normal levels 3 hours following TNFalpha treatment.
	0.97	IkappaBalpha protein levels at 2 hours post-treatment and there was little change in IkappaBalpha intensity upon subsequent stimulation with TNFalpha (Figure 6A, C).
	0.96	IkappaBalpha protein levels in basal conditions, and induced up-regulation of NF-kappaB target genes, we next tested the effect of sulindac sulfide on IkappaBalpha in conditions where the canonical NF-kappaB pathway is activated through stimulation by the cytokine TNFalpha.
	0.95	TNFalpha stimulated conditions the drug treatment inhibited phosphorylation on IkappaBalpha (Ser 32) which is consistent with previous studies and indicates that sulindac sulfide can inhibit TNFalpha-induced NF-kappaB activation.
	0.95	IkappaBalpha phosphorylation and degradation in sulindac sulfide and TNFalpha-treated cells.
	0.94	IkappaBalpha showed that sulindac sulfide pre-treatment in the absence of TNFalpha did not increase IkappaBalpha phosphorylation on Ser32, whereas TNFalpha stimulation induced rapid IkappaBalpha phosphorylation on Ser32.
	0.93	TNFalpha-induced IkappaBalpha phosphorylation and degradation.
25888769	0.97	IkappaB-alpha (p-IkappaB-alpha Ser32) and of nuclear p65 component (p-NF-kappaB Ser536) in control and TRAPS PBMCs kept in culture for 24 hours unstimulated or stimulated with TNF and IL-1beta.
	0.96	IkappaB-alpha and p65 nuclear subunit of NF-kappaB expression in all mutants in the presence of TNF or IL-1beta stimulation.
	0.96	TNF and IL-1beta on two key NF-kappaB signaling molecules, p-IkappaB-alpha (Ser32) and p65 component (p-NF-kappaB (Ser536)), were assessed by Western blot analysis in WT, S59P, R92Q and T50M HEK-293, and in PBMCs obtained from TRAPS patients and controls.
	0.87	TNF receptor triggers a set of cascade events, including IKK complex activation, phosphorylation and IkappaB-alpha degradation, and activation and nuclear translocation of the NF-kappaB complex that in turn modulates the expression of a sequence of pro-inflammatory genes.
	0.70	TNF reduced IkappaB-alpha phosphorylation.
	0.62	TNF and IL-1beta reduced the phosphorylation of IkappaB-alpha (p-IkappaB-alpha Ser32) in WT cells, while the opposite was found when they were added to S59P and T50M mutant cells.
	0.61	TNF and IL-1beta induced the phosphorylation of IkappaB-alpha, which was higher and more persistent in T50M and S59P than in the WT TNFRSF1A cells.
20978115	0.97	IkappaBalpha showed that TNF induced IkappaBalpha phosphorylation and that thiocolchicoside suppressed both this phosphorylation (Fig. 5B, left) and IkappaBalpha ubiquitination (Fig. 5B, right).
	0.94	TNF-induced IkappaBalpha degradation was due to inhibition of IkappaBalpha phosphorylation and ubiquitination, we used the proteasome inhibitor ALLN to block the degradation of IkappaBalpha.
	0.93	TNF-induced phosphorylation of IkappaBalpha and because thiocolchicoside inhibited the phosphorylation of IkappaBalpha, we determined the effect of thiocolchicoside on TNF-induced IKK activation.
	0.90	TNF induced IkappaBalpha degradation in control cells after 10 minutes, and thiocolchicoside inhibited this degradation (Fig. 5A, right).
	0.88	TNF-induced NF-kappaB activation and IkappaBalpha degradation, as well as phosphorylation.
	0.56	TNF), okadaic acid (OA), tumor promoter [phorbol 12-myristate 13-acetate (PMA)], and lipopolysaccharide (LPS) through inhibition of phosphorylation, ubiquitination, and degradation of inhibitory kappaBalpha (IkappaBalpha), the inhibitor of NF-kappaB. Thiocolchicoside also inhibited the phosphorylation and nuclear translocation of p65, the major isoform of NF-kappaB. Thiocolchicoside inhibition of NF-kappaB leads to suppression of NF-kappaB-regulated proteins, which are responsible for the anticancer effect of thiocolchicoside on various cancer cell lines, characterized by induction of apoptosis and inhibition of cell proliferation as well as colony formation.
21908405	0.97	TNFalpha exposure led to marked IkappaBalpha phosphorylation, strong DNA binding as well as 4-fold (P = 0.0039) increased NF-kappaB-dependent GFP transcription.
	0.96	IkappaBalpha-SR both basal (3.5-fold) and TNFalpha-induced (2.7-fold) DSB repair was down-regulated (P < 0.01; Figure 1B).
	0.96	TNFalpha-mediated induction of DSB repair could still be detected in cells expressing IkappaBalpha-SR, a NF-kappaB-independent effect of TNFalpha action is conceivable.
	0.96	IkappaBalpha-SR expression compromised DNA binding and GFP expression in TNFalpha-treated samples.
	0.96	TNFalpha-treatment, we measured a 9.3-fold (P = 0.0117) HR increase which was abrogated in the presence of IkappaBalpha-SR (P > 0.05) (Supplementary Figure S6C).
	0.70	TNFalpha- and mock treated nor between IkappaBalpha-SR expressing and control samples regarding sub-G1, G1-, S- or G2-phase fractions (Figure 1D and E).
25229347	0.97	TNF-alpha-induced activation of IKK and IkappaBalpha degradation.
	0.95	IkappaBalpha phosphorylation and TNF-alpha-induced nuclear translocation of NF-kappaB subunits of p65 were also antagonized by leukotriene B4 receptor antagonist LY29311 (figure S1).
	0.90	TNF-alpha-induced IKKalpha/beta activation, IkappaBalpha phosphorylation, IkappaBalpha degradation and NF-kappaB nuclear translocation in human synovial fibroblasts.
	0.89	TNF-alpha (10 ng/ml) enhanced the phosphorylation of IkappaBalpha time-dependently in human synovial fibroblasts.
	0.83	TNF-alpha (10 ng/ml) enhanced the phosphorylation of IkappaBalpha time-dependently in human synovial fibroblasts, and the phosphorylation of IkappaBalpha reached a peak at 10 min (Figure 5A).
	0.63	TNF-alpha-induced cytokine expression in human synovial fibroblasts, IKKalpha/beta activation, IkappaBalpha phosphorylation, and IkappaBalpha degradation were evaluated by immunoblotting after stimulation by TNF-alpha.
27641334	0.97	TNF engages NEMO (nuclear factor-kappaB (NFkappaB_ essential modulator)-IKK2 (IkappaB kinase subunit 2, also known as IKKbeta) kinase complex, which promotes phosphorylation and degradation of inhibitory IkappaBalpha (inhibitor of NF-kappaBalpha), thereby, liberating RelA:p50 dimer into the nucleus via the canonical NFkappaB pathway.
	0.93	IkappaBalpha control, whose degradation during TNF signaling induced an early RelB:p50 containing NFkappaB activity.
	0.91	IkappaBalpha mediated regulations and RelA-induced synthesis control, are inadequate to account for the prolonged RelB:p50/NFkappaB response during canonical TNF signaling.
	0.91	TNF-induced nuclear activation of RelB/NFkappaB dimer in IkappaBalpha-deficient MEFs was revealed in RelB-EMSA.
	0.83	TNF signaling to impart drug resistance in myeloma cells independent of the principal NFkappaB subunit RelA. Interestingly, these mutations did not act through typical p52 NFkappaB complexes, but depleted p100 to reposition RelB under IkappaBalpha control.
	0.60	TNF stimulation that further weakened RelB-IkappaBalpha interaction.
19934328	0.97	TNF-alpha neutralizing antibody totally abolished the TNF-alpha induced reduction of IkappaBalpha, AR and PSA expression (Fig.1C left).
	0.96	TNF-alpha-induced AR repression, we blocked NF-kappaB activation with an IkappaBalpha super suppressor (pcDNA-IkappaBalphaSS/AA-HA) to test whether TNF-alpha-induced AR suppression requires NF-kappaB activation.
	0.94	TNF-alpha-induced IkappaBalpha phosphorylation and NF-kappaB activation.
	0.91	TNF-induced IkappaBalpha phosphorylation was inhibited significantly (56% reduction).
	0.87	IkappaBalpha in LNCaP and C4-2B cells after 1 hour treatment with 20ng/ml TNF-alpha.
29162874	0.97	IkappaBalpha is degraded, a noticeable fraction of NF-kappaB remains cytoplasmic (Fig. 1b), possibly because it is sequestered by other inhibitors that are not degraded in response to TNF or because some post-translational modifications preclude its nuclear translocation.
	0.97	IkappaBalpha (Nfkbia) and A20 (Tnfaip3) mRNA accumulate over 3-4 hours after TNF or LPS stimulation (Fig. 1d), indicating transcriptional activity, however, no IkappaBalpha proteins are visible in immunostaining images at the end of that period, and most of NF-kappaB reside in the nucleus (Fig. 1b), as also observed by Sung et al.. Notwithstanding, in cells stimulated with TNF or LPS without CHX pretreatment, IkappaBalpha mRNA profile peaks at about 1 hour, and IkappaBalpha protein accumulates over 3 hours and directs NF-kappaB out of the nucleus.
	0.95	IkappaBalpha-mediated feedbacks by incubation with CHX leads to prolonged NF-kappaB activation in responses to TNF or LPS.
	0.92	TNF or LPS resulted in markedly increased levels of IkappaBalpha and A20 mRNA at 3 hr/4 hr after TNF/LPS stimulation.
	0.76	TNF, fixed and stained with antibodies for RelA (a subunit of NF-kappaB) and IkappaBalpha.
21572963	0.97	TNF-alpha-induced IkappaBalpha degradation
	0.93	IkappaBalpha degradation, but also attenuated the nuclear translocation of NF-kappaB. This provides evidence that H2S can attenuate TNF-alpha-induced NF-kappaB activation, as previously reported.
	0.91	IkappaBalpha degradation was analyzed by Western blot in HUVEC stimulated with TNF-alpha (10 ng/ml) for indicated periods.
	0.63	TNF-alpha-induced IkappaBalpha degradation in a concentration dependent manner.
29109532	0.97	TNF-alpha-stimulated FLAG-IkappaBalpha degradation (Fig. 3B).
	0.97	IkappaBalpha, we knockdowned IkappaBalpha expression with siRNA and analyzed the p65 nuclear translocation in NMI-expressing HeLa cells after TNF-alpha stimulation.
	0.96	TNF signaling, significantly inhibited TNF-alpha-stimulated IkappaBalpha degradation (Fig. 3C and Supplementary Fig. 4).
	0.92	TNF-alpha-induced NF-kappaB activation, we examined the effect of NMI on\ TNF-alpha-induced IkappaBalpha degradation.
19243468	0.97	IkappaBalpha, which strongly supports an apoptotic role for HSP70 in TNFalpha-induced apoptosis.
	0.92	IkappaBalpha-NFkappaB and the expression of anti-apoptotic molecules (e.g. Bcl-xl and c-IAP1) induced by TNFalpha.
	0.79	TNFalpha treatment (20 ng/ml) was about 1.35 folds to that in Ctrl siRNA-transfected cells; **, the relative signal intensity of p-IkappaBalpha to input IKKbeta in HSP70-silenced cells 60 min.
19561104	0.97	IkappaBalpha kinase (IKK) complex and MAPK followed by dissociation of IkappaBalpha, nuclear translocation, and DNA binding of NFkappaB to the promoter region of target genes such as adhesion molecules and proinflammatory cytokines particularly, TNF-alpha, IL-1beta, and IL-6.
	0.91	IkappaBalpha degradation results in NFkappaB translocation, DNA binding, and transactivation of target genes such as TNF-alpha.
	0.91	TNF-alpha production was due to increased IRAK kinase, increased NFkappaB activity, and less IkappaBalpha protein levels, a lack of IRAK-M induction, and decreased TLR4 expression.
21618526	0.97	TNF (100 U/ml) for 5-30 min were immunoblotted with antibodies to phospho-IkappaBalpha (Ser32; P-IkappaBalpha), IkappaBalpha, phospho-65 (Ser536; P-p65).
	0.79	IkappaBalpha phosphorylation and degradation, and less p65 phosphorylation in HGF-treated versus TNFalpha-treated RPTEC.
	0.70	TNFalpha treatment, in contrast, led to significantly greater phosphorylation of IkappaBalpha and p65, followed by a complete degradation of IkappaBalpha within 15 min of adding TNFalpha (Fig. 3).
25795708	0.96	TNFalpha-induced IkappaBalpha degradation was stronger in MCF-7 cells expressing higher levels of RXRalpha and tRXRalpha than in H460 cells with much lower RXRalpha and tRXRalpha expression (Fig. 4D).
	0.96	TNFalpha-stimulated NFkappaB transcriptional activity and IkappaBalpha degradation (Supplementary Fig. S5A and B).
	0.96	TNFalpha activation of NFkappaB. When TRAF2 expression was suppressed by siRNA-mediated knockdown, the effect of Z-12 on inhibiting TNFalpha-induced IkappaBa degradation was dramatically reduced, indicating the role of TRAF2 in the activity of Z compounds (Fig. 5C).
	0.96	TNFalpha-induced IkappaBalpha degradation.
	0.95	TNFalpha-induced IkappaBalpha degradation.
	0.94	TNFalpha-induced IkappaBalpha degradation (Supplementary Fig. S4E).
	0.94	TNFalpha-induced IKK phosphorylation and IkappaBalpha degradation.
	0.93	TNFalpha-induced p65 nuclear translocation, IkappaBalpha degradation and IKKalpha/beta phosphorylation (Fig. 4B, 4C and Supplementary Fig. S4C).
	0.93	TNFalpha-induced IkappaBalpha degradation (Supplementary Fig. S4D).
	0.93	TNFalpha-induced IkappaBalpha degradation was reduced (Fig. 4E).
	0.93	TNFalpha, tumor necrosis factor alpha; IkappaBalpha, NF-Kappa-B Inhibitor alpha; DAPI, 4',6-diamidino-2-phenylindole.
	0.87	TNFalpha (10 ng/ml) for the indicated time, and IKKalpha/beta phosphorylation and IkappaBalpha expression were analyzed by immunoblotting.
	0.85	TNFalpha-induced IkappaBalpha degradation (Supplementary Fig. S4F).
	0.84	TNFalpha-induced IkappaBalpha degradation and RXRalpha/tRXRalpha expression.
14641910	0.96	IkappaB-alpha, ICAM-1 and TNF-alpha.
	0.96	TNF-responsive genes in U373 cells and to inhibit NF-kappaB target genes pharmacologically with PDTC, IkappaB-alpha expression was analyzed by Northern blotting.
	0.96	IkappaB-alpha by TNF is blocked by cotreatment with PDTC.
	0.96	TNF regulated, such as tumor necrosis factor induced protein 2 (TNFAIP2, B94), IkappaB-alpha or VCAM-1.
	0.95	IkappaB-alpha was readily detected after 1 h and peaked after 1 h of TNF treatment (Fig. 1a).
	0.95	IkappaB-alpha expression, PDTC pre-treatment blocked the TNF effect on IkappaB-alpha expression (Fig. 1B).
	0.95	IkappaB-alpha in U373 cells after TNF treatment (A) or PDTC and TNF cotreatment (B).
	0.91	TNF target genes, e.g. constituents of transcription factors: IkappaB-alpha and IRF-1 (NFKBIA, IRF1).
	0.87	TNF regulates IkappaB-alpha expression in U373 glioblastoma cells
24324738	0.96	TNFA -308 polymorphism was the best one factor model and TNFA -308 and NFKBIA 3'UTR were the best model for two factors and TNFA-308, NFKBIA -826, NFKBIA 3'UTR polymorphisms as best model for three factors.
	0.94	TNFA -308GA genotype was associated with increased risk of ESCC specifically in females and in patients with regional lymph node involvement, while, NFKBIA -826CT+TT genotype conferred decreased risk of ESCC in females.
	0.94	TNFA-308 G>A, NFKB1 -94ATTG ins/del and NFKBIA (-826 C>T and 3'UTR A>G) polymorphisms
	0.92	TNFA -308 G>A polymorphism and combined effect of TNFA and NFKBIA gene polymorphisms in susceptibility of ESCC in northern Indian population.
	0.89	TNFA-308, NFKBIA-826, NFKBIA 3'UTR as better predictor for risk of ESCC.
	0.87	TNFA, NFKB1 and NFKBIA were in accordance with HWE in controls (P>0.05 in each case).
	0.84	TNFA -308, NFKBIA -826 and NFKBIA 3'UTR polymorphisms as better predictor for risk of ESCC.
	0.67	TNFA-308 G>A, NFKB1 -94ATTG ins/del and NFKBIA polymorphisms with clinical characteristics (tumour location and regional lymph node involvement) of ESCC
	0.55	TNFA, NFKB1 and NFKBIA (the major mediators of inflammatory and immune response in malignancy) with risk and prognosis of ESCC in northern Indian population.
22768286	0.96	TNF-alpha-Induced Activation of IkappaBalpha Kinase, p65 Phosphorylation, and
	0.95	TNF-alpha-induced phosphorylation and degradation of IkappaBalpha (Fig. 2B, right five lanes), and this inhibitory effect was also observed in a dose-dependent manner (Fig. 2C).
	0.95	TNF-alpha-induced activation of NF-kappaB through inhibition of phosphorylation and degradation of IkappaBalpha.
	0.95	TNF-alpha-induced NF-kappaB activation pathway, which is mediated through the sequential interaction of TNFR and TRADD, TRAF2, NIK, and IKK, results in the phosphorylation and degradation of IkappaBalpha to realease NF-kappaB, we further examine the effects of cryptopleurine on the TNF-alpha-induced NF-kappaB activation pathway in the MDA-MB231 cells transfected with the NF-kappaB-regulated luciferase reporter gene and plasmids expressing TNFR1, TRAF2, RIP, NIK, IKK, or p65.
	0.94	TNF-alpha induced phosphorylation and degradation of IkappaBalpha were also occurred as quickly as 5 min (Fig. 2B, left five lanes).
	0.93	TNF-alpha-induced IkappaB kinase (IKK) activation, thereby blocking the activation of NF-kappaB through the inhibition of IkappaBalpha phosphorylation and degradation, and p65 nuclear translocation and DNA-binding activity.
	0.91	TNF-alpha-Induced IkappaBalpha Phosphorylation and Degradation
	0.90	TNF-alpha-induced activation of IkappaBalpha kinase, p65 phosphorylation, and p65 nuclear translocation.
25849741	0.96	TNF-alpha stimulation, IkappaBalpha proteins are phosphorylated and as a consequence degraded, thus providing a positive control for our data set.
	0.91	NF-kappa-B inhibitor alpha (IkappaBalpha) protein with a 22-fold upregulation on TNF-alpha stimulation, whereas treatment of SC-514 showed a significant downregulation (53%).
	0.84	IkappaBalpha) on TNF-alpha stimulation; however, this effect was abolished on SC-514 treatment or on the overexpression of the kinase dead IKKbeta (K44M), thus proving the basal functionality of the experimental conditions (Fig. 1c,d).
	0.77	TNF-alpha-mediated gene expression, including the degradation of IkappaBalpha and p65-mediated activation of gene transcription, but not for translocation of p65 and AEG-1 to the nucleus.
	0.67	TNF-alpha pathway is the regulation of gene expression through IkappaBalpha-kinase-complex (IKK complex)-mediated degradation of IkappaBalpha and the subsequent activation of the transcription factor NF-kappaB. Although regulation of IkappaBalpha degradation is believed to be the major cellular function of the IKK complex members, there is growing evidence that the IKK complex has additional functions and modulates other cellular processes, including insulin signal transduction.
	0.60	TNF-alpha-induced IkappaBalpha degradation and subsequent activation of NF-kappaB-dependent cellular processes.
27671354	0.96	TNF-induced IkappaBalpha degradation and p65 translocation
	0.95	TNF pathway, we first investigated the degradation of IkappaBalpha and the nuclear translocation of NF-kappaB, which are the two biochemical hallmarks of NF-kappaB activation.
	0.95	TNF-induced NF-kappaB-dependent genes expressions, IkappaBalpha degradation and p65 nuclear translocation.
	0.92	TNF-induced IKK activation was significantly reduced as measured by the in vitro IKK kinase assay as well as the immunoblotting of p-IkappaBalpha in the total cell extracts (Fig. 3a, upper panel).
	0.71	IkappaBalpha degradation, we observed a significant reduction of TNF-induced p65 nuclear translocation in JMJD8-deficient cells (Fig. 2a, lower panel).
23468625	0.96	IkappaBalpha despite lacking all known inhibitors of TNFalpha-mediated NF-kappaB activation.
	0.92	TNFalpha, accumulation of p-IkappaBalpha and IkappaBalpha during vA49rev infection was also detected (as observed by conventional immunoblotting), but with the sample sizes tested this was not significant.
	0.90	IkappaBalpha were observed upon TNFalpha activation, but these were reduced in the presence of A49 (Figure 6C).
	0.73	TNFalpha stimulation, IkappaBalpha was immunoprecipitated.
22437419	0.96	TNF rapidly induced the phosphorylation and degradation of IkappaBalpha in HASMCs; consistently, TNF stimulated the nuclear translocation of p65, which was blocked by IKK inhibition (IKKbetaVI, 2 muM) (Figure 3B).
	0.77	TNF, but Ad-IkappaBalpha maintained the expression of ANKH and decreased TNF-accelerated calcification (Supplemental Figure 2).
	0.73	TNF strongly induced the expression of NF-kappaB target genes, including interleukin 8 (IL-8), IkappaBalpha, and monocyte chemoattractant protein 1 (MCP-1) (Figure 3A), all associated with vascular inflammation.
21973049	0.96	IkappaBalpha protein decreased in response to TNF-alpha treatment, mutant-IkappaBalpha protein was stably detected even after treatment with TNF-alpha.
	0.93	TNF-alpha-induced suppression of AQP5 expression in NS-SV-AC cells, we detected similar TNF-alpha suppression of AQP5 expression in non-transfected cells and in a super-repressor form of IkappaBalpha cDNA-transfected cell clones.
29900006	0.95	IkappaBalpha complex in the cytoplasm and free, non-phosphorylated NFkappaB in the nucleus were simulated for TNFalpha concentrations between 0.1 and 1000 ng/ml.
	0.95	TNFalpha-induced IKK phosphorylation similar to DCF, whereas the effect on IkBalpha was barely noticeable.
	0.95	TNFalpha-induced NFkappaB signal transduction using IKK phosphorylation and IkBalpha production/degradation as major characteristics of DILI compounds within the TNFalpha-induced NFkappaB signaling pathway.
	0.93	TNFalpha concentration of 10 ng/ml lead to the dissociation of almost all NFkB:IkBalpha complexes.
	0.93	IkappaBalpha influx exceeds the NFkappaB influx is shown as dashed black line for TNFalpha and as dashed red line for TNFalpha and DCF.
	0.89	TNFalpha concentrations above the experimentally applied 10 ng/ml of TNFalpha resulted in an increase of IKK phosphorylation levels but not in an increase in the peak height of nuclear NFkB. This effect can be understood from the predicted dynamics of the NFkB:IkBalpha complex concentration.
	0.88	IkappaBalpha complex, we performed co-immunoprecipitation experiments (Co-IP) in HepG2 cells that were stimulated with TNFalpha.
	0.86	IkappaBalpha, pIkappaBalpha, pIKK, and pNFkB levels were measured by quantitative immunoblotting in HepG2 cells treated with either TNFalpha alone (10 ng/ml) or TNFalpha (10 ng/ml) and the respective compound (n = 3-4, raw data in Figs. S30-S45).
	0.83	TNFalpha-induced IKKbeta-mediated and IkappaBalpha-mediated regulation of NFkappaB signal transduction as a tool to quantify the impact of drug-induced liver injury compounds
	0.83	TNFalpha concentrations as low as 0.1 ng/ml, more than 90% of all NFkB:IkBalpha complexes dissociated.
	0.81	IkappaBalpha regulation it was possible to quantify the impact of four additional DILI compounds (amiodarone, paracetamol, ximelagatran, and fialuridine) on TNFalpha-induced NFkappaB activation.
	0.75	TNFalpha, the recovery of iIKK, the phosphorylation of pIKK, the phosphorylation of IkBalpha by pIKK, the production and degradation of IkBalpha mRNA, and, finally, the translation of A20 mRNA were introduced into the model yielding the TNFalpha signaling DCF model.
	0.74	IkappaBalpha and of NFkappaB in response to TNFalpha (black line) and upon TNFalpha and DCF co-treatment (red line).
	0.63	IkappaBalpha, and NFkappaB phosphorylation the cytoplasmic levels of IkappaBalpha reached the lowest values after TNFalpha stimulation at 20 min in both HepG2 cells and PHH.
25893721	0.95	TNFalpha stimulation; (2) the complex of PTPIP51/RelA/IkappaBa has a regulatory function on all complexed proteins; and (3) that PTPIP51 probably links the NFkappaB signaling to the MAPK pathway in cooperation with RelA.
	0.85	IkappaBalpha under the influence of TNFalpha (p > 0.05).
	0.85	TNFalpha treated cells, 100 ng/mL TNFalpha treated cells, 200 ng/mL TNFalpha treated cells, 400 ng/mL TNFalpha treated cells, 500 ng/mL TNFalpha treated cells. * (p < 0.05), ** (p < 0.01); (B) PTPIP51 and IkBalpha interactions.
	0.59	IkappaBalpha, the inhibitory protein of RelA. After a transient TNF-alpha stimulation RelA initiates resynthesis of IkappaBalpha as a potent negative feedback resulting in the rapid termination of RelA activity.
	0.53	IkappaBalpha complex is modulated by TNFalpha.
29968158	0.95	IkappaBalpha-/- vascular cells and downregulated genes in RelA-/- vascular cells compared to WT vascular cells upon TNFalpha treatment.
	0.93	IkappaBalpha-/- vascular cells (pink), downregulated only in RelA-/- vascular cells (green) and genes overlapped (blue) upon TNFalpha treatment.
21820422	0.94	TNF-induced IkappaBalpha phosphorylation and ubiquitination needed for IkappaBalpha degradation, we blocked degradation of IkappaBalpha with the proteasome inhibitor N-acetyl-leucyl-leucyl-norleucinal (ALLN).
	0.93	TNF-induced IkappaBalpha degradation
	0.93	TNF induced IkappaBalpha degradation in control cells as early as 10 min after treatment, but in triptolide-treated cells TNF-induced IkappaBalpha degradation was decreased but not completely reversed (Fig. 4A).
	0.82	IkappaBalpha degradation is required for activation of NF-kappaB, we investigated whether triptolide inhibits TNF-induced NF-kappaB activation by inhibiting IkappaBalpha degradation.
	0.82	IkappaBalpha showed that TNF-induced IkappaBalpha phosphorylation and ubiquitination were strongly suppressed by triptolide (Fig. 4B upper).
19123467	0.94	IkappaBalpha-M or control vector (Western blot -- bottom panel) with or without TRAIL or TNFalpha treatment for 24 hours.
	0.91	IkappaBalpha-M sensitizes prostate cancer cells to TRAIL- and TNFalpha-induced apoptosis.
	0.62	IkappaBalpha-M were partially sensitized to TNFalpha (PC3 and PC3-TR cells) and TRAIL (PC3-TR cells) by demonstrating a lower percentage of viable cells (Fig. 4 A and B - lower panels).
28715653	0.94	IkappaBalpha phosphorylation by nsp1 after TNFalpha treatment for 5 min (Fig. 7E).
	0.67	IkappaBalpha was reduced, and the amount of IkappaBalpha was stable in nsp1-expressing cells as well as in PRRSV nsp1alpha-expressing control cells when treated with TNFalpha (Fig. 7D).
19152111	0.93	IkappaBalpha (200 moi) or control vector and then incubated with TNFalpha (10 ng/ml) for the indicated time periods.
	0.91	IkappaBalpha (200 moi) or control adenoviral vector, followed by incubation with TNFalpha (10 ng/ml) or PBS for 2 hours.
	0.68	IkappaBalpha (50 moi) (A-D) or 200 moi (E,F) followed by incubation with TNFalpha (10 ng/ml) for 16 hours (B-D) or 4 hours (E, F), respectively.
	0.66	IkappaBalpha vectors and then incubated with control medium or with TNFalpha for 2 hours.
	0.63	IkappaBalpha (200 moi) or the control vector, followed by incubation with TNFalpha (10 ng/ml) for 16 hours.
29703889	0.93	IkappaBalpha degradation was blocked by TPCA-1 but not by necroptosis inhibitors (Supplementary Figure 9c-e), and TNFalpha alone induced IkappaBalpha degradation was not affected by NSA (Supplementary Figure 9f), indicating that the RIPK1 kinase activity, RIPK3, and MLKL were specifically required for the second wave of IkappaBalpha degradation.
	0.90	IkappaBalpha during necroptosis was much stronger than that triggered by TNFalpha alone (Fig. 5a and Supplementary Figure 7a).
	0.83	IkappaBalpha ubiquitination in cells treated with TSZ was significantly stronger than that induced by TNFalpha alone, which was blocked by IKK inhibition, and by Nec-1s, GSK872, NSA, or silencing MLKL (Fig. 6f-h).
27185527	0.93	TNFalpha treatment of SK-N-AS cell populations transiently expressing EGFP-E2F-1 and RelA-DsRedxp led to reduced levels of phospho-S536-RelA and stabilized levels of IkappaBalpha (Figure 6E).
25419573	0.92	TNF-alpha sensitized breast cancer cells to WA or Cel by enhancing the inhibition of cellular proteasome activities, we studied the cellular proteasomal CT-like activity and accumulation of ubiquitinated proteins and the proteasome target protein, IkappaBalpha.
	0.91	TNF-alpha plus Cel on CT-like activity, ubiquitinated proteins and IkappaBalpha.
	0.88	TNF-alpha plus Cel on proteasomal activity, ubiquitinated proteins and IkappaBalpha.
	0.82	TNF-alpha plus WA on proteasomal activity, ubiquitinated proteins and IkappaBalpha.
	0.63	TNF-alpha plus WA on CT-like activity, ubiquitinated proteins and IkappaBalpha.
27713151	0.92	TNFalpha exposure abrogated TNFalpha induced NF-kappaB and IkappaB-alpha phosphorylation, protecting IkappaB-alpha from degradation and preventing the activation of the NF-kappaB complex (Figure 6A and see Figure 3B).
	0.92	IkappaB-alpha after treatment with 20ng/mL TNFalpha or/and 1muM selinexor for 24 hours.
	0.90	IkappaB-alpha and phosphor-NF-kappaB p-65 shows that selinexor reverts the pro-inflammatory effects of TNFalpha and selinexor also increased cellular levels of IkappaB-alpha.
	0.84	TNFalpha mediated phosphorylation is inhibited by selinexor in a dose dependent manner, protecting IkappaB-alpha from degradation and preventing phosphorylation and activation of the NF-kappaB complex.
	0.69	TNFalpha-induced transcriptional activity of NF-kappaB. Our studies demonstrate that this is achieved through the inhibition of XPO1-mediated nuclear export of key members of the NF-kappaB pathway, namely NF-kappaB p65 subunit and IkappaB-alpha.
25380350	0.92	IkappaBalpha-SR in HaCaT-p53i cells (Figure 3e) minimized both, apoptosis enhancement (Figure 3f) and TNF release (Figure 3g).
	0.92	IkappaBalpha-SR cells were treated as in a, apoptosis was determined with Cell Death Detection ELISA, and (h) TNF release was documented with TNF ELISA.
	0.88	TNF release and thereby IL-1-mediated enhancement of UVB-induced apoptosis was minimized in HaCaT-p53i-IkappaBalpha-SR cells.
	0.84	IkappaBalpha-SR, and -p53i/IkappaBalpha-SR cells were stimulated as in d. Apoptosis was determined with Cell Death Detection ELISA (n-fold enhancement of apoptosis is indicated) and (g) TNF release with TNF ELISA.
22261743	0.91	IkappaBalpha-/- 3T3 were treated with TNF for 15 min and then either left untreated or stimulated with MG132 for 1, 3, and 6 hours, cells were processed for immunofluorescence with RelA antibody.
	0.90	IkappaBalpha-/- 3T3 were stimulated with a pulse of TNF for 15 min, then either left untreated or incubated with beta-lactone or MG132 for 6 hours.
	0.89	IkappaBalpha absence, nuclear RelA was completely cleared over the time course of 6 hours medium after a pulse of 15 min TNF.
29065968	0.91	TNF-alpha, the cytosolic NF-kappaB heterodimer is freed from IkappaBalpha and translocates into the nucleus, where it activates the transcription of proinflammatory genes.
21754991	0.89	IkappaBalpha and nuclear translocation of p50 (NF-kappaB1) in TNF-alpha endothelial cells (L Michel and M Applanat, not shown).
	0.68	TNF-alpha treated HMEC in the presence of Bay11-7082 (a specific inhibitor of cytokine-induced IkappaBalpha phosphorylation), is in agreement with the involvement of this pathway.
21383764	0.86	IkappaBalpha, NF-kappaB inhibitor-alpha (also known as NF-kappaBIalpha); IKK, IkappaB kinase; IRAK, IL-1R-associated kinase; KSHV, Kaposi's sarcoma-associated herpesvirus; LMP1, latent membrane protein 1; L. pneumophila, Legionalla pneumophila; MYD 88, myeloid differentiation primary response protein 88; NEMO, NF-kappaB essential modulator (also known as IKKgamma); RIP1, receptor-interacting protein 1 (also known as RIPK1); R. rickettsii, Rickettsia rickettsii; RSV, respiratory syncytial virus; SCFbetaTRCP, SKP1, cullin 1 and F-box protein betaTRCP; S. flexneri, Shigella flexneri; Stp, Saimiri transformation-associated protein; TAK1, TGFbeta-activated kinase 1; T. gondii, Toxoplama gondii; TLR, Toll-like receptor; TNFR, TNF receptor; TRAF, TNFR-associated factor; Ub, ubiquitin.
	0.83	IkappaBalpha, NF-kappaB inhibitor-alpha (also known as NF-kappaBIalpha); IKK, IkappaB kinase; IL-1R, interleukin-1 receptor; NEMO, NF-kappaB essential modulator (also known as IKKgamma); NIK, NF-kappaB-inducing kinase (also known as MAP3K14); TLR, Toll-like receptor; TNFR, TNF receptor.
23612498	0.86	TNFalpha-induced IkappaBalpha phosphorylation is robust and immediate, resulting in complete degradation of IkappaBalpha within 15 minutes post-stimulation.
	0.62	TNFalpha-induced transient IKK activation or IkappaBalpha degradation, though it does result in reduced NF-kappaB-dependent gene expression.
17925009	0.75	tumor necrosis factor-alpha (TNFalpha) and interleukin-1 (IL-1) bind to cell surface receptors coupled to the cytoplasmic IkappaB kinase (IKK), a multiprotein complex that phosphorylates IkappaBalpha, leading to its ubiquitination and then to its rapid proteasomal degradation.
	0.54	TNFalpha dose of 10 or 1 ng/ml is much higher than needed for efficient IkappaBalpha degradation.
24509793	0.74	TNFalpha-treated BT549 cells and immunoblotted with antibodies to alpha-catenin and IkappaBalpha.