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IKBKB — TNF

Pathways - manually collected, often from reviews:

• OpenBEL Selventa BEL large corpus: IKBKB → TNF (increases, TNF Activity)
  Evidence: Figure 1. Pathways to MUC5AC expression in COPD
• OpenBEL Selventa BEL large corpus: IKBKB → TNF (increases, TNF Activity)
  Evidence: TNF- treatment induced substantial activation of IKK, as reflected by IB phosphorylation (Figure 4C).
• OpenBEL Selventa BEL large corpus: IKBKB → TNF (increases, TNF Activity) Prajapati et al., J Biol Chem 2004*
  Evidence: The NF-kappaB pathway is important in the control of the immune and inflammatory response. One of the critical events in the activation of this pathway is the stimulation of the IkappaB kinases (IKKs) by cytokines such as tumor necrosis factor-alpha and interleukin-1.
• OpenBEL Selventa BEL large corpus: IKBKB → TNF (increases, TNF Activity) Varfolomeev et al., J Biol Chem 2005*
  Evidence: By contrast, TNF primarily induces gene transcription through the inhibitor of kappaB kinase (IKK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase pathways.
• OpenBEL Selventa BEL large corpus: IKBKB → TNF (increases, TNF Activity) Cusson-Hermance et al., J Biol Chem 2005
  Evidence: Rip1 is required for IkappaB kinase activation in response to tumor necrosis factor alpha (TNF-alpha) and has been implicated in the Toll-like receptor 3 (TLR3) response to double-stranded RNA.
• OpenBEL Selventa BEL large corpus: IKBKB → TNF (increases, TNF Activity) Chen et al., J Immunol 2000*
  Evidence: The endogenous IKK complex was isolated by immunoprecipitation with anti-IKKb Ab and tested for in vitro kinase activity. As shown in Fig. 13, both TNF-a and TPA induced IKK activation, and these effects were inhibited by staurosporine and herbimycin.
• OpenBEL Selventa BEL large corpus: IKBKB → TNF (increases, TNF Activity) Newton et al., J Pharmacol Exp Ther 2007*
  Evidence: In A549 cells, IKK kinase activity is maximal within 5 min of TNF stimulation, and both IL-1 and TNF lead to substantial losses of IB within this time frame (Newton et al., 1998a; Catley et al., 2004).
• OpenBEL Selventa BEL large corpus: IKBKB → TNF (increases, TNF Activity)
  Evidence: In the case of NF-kappaB, external stimuli such as TNF-alpha and IL-1beta signal through specific receptors to activate the IKK2.
• OpenBEL Selventa BEL large corpus: IKBKB → TNF (increases, TNF Activity) Peters et al., Mol Cell 2000*
  Evidence: This led to the identification of a high molecular weight IkBalpha kinase complex capable of phosphorylating IkBalpha specifically on serines 32 and 36. Subsequently, the same complex was isolated from TNFalpha-induced HeLa cells and found to contain two IkBalpha kinases, designated IKKalpha and IKKbeta (or IKK1 and IKK2). These kinases were cloned and shown to be activated by TNFalpha, IL-1, and PMA.
• OpenBEL Selventa BEL large corpus: IKBKB → TNF (increases)
  Evidence: TNF- treatment induced substantial activation of IKK, as reflected by IB phosphorylation (Figure 4C).
• KEGG Type II diabetes mellitus: TNF → IKBKB (protein-protein, indirect effect)
• NCI Pathway Database Canonical NF-kappaB pathway: TNF/TNFR1A complex (TNF-TNFRSF1A) → IKK complex complex (CHUK-IKBKB-IKBKG) (modification, activates)
  
• NCI Pathway Database TNF receptor signaling pathway : sTNF-alpha/TNFR1A/TRADD/RIP/TRAF2/TAK1/TAB family/MEKK3 complex (TNFRSF1A-TRADD-RIPK1-TRAF2-MAP3K3-MAP3K7-TAB2_TAB1-TNF) → IKK complex complex (CHUK-IKBKB-IKBKG) (modification, activates)
  Devin et al., Immunity 2000, Yang et al., Nat Immunol 2001, Ducut Sigala et al., Science 2004, Blonska et al., J Biol Chem 2005
  Evidence: mutant phenotype, assay, physical interaction

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

• IRef Biogrid Interaction: TNF — IKBKB (physical association, affinity chromatography technology) Ea et al., Mol Cell 2006
• IRef Biogrid Interaction: TNF — IKBKB (physical association, affinity chromatography technology) Haas et al., Mol Cell 2009

Text-mined interactions from Literome

Lallena et al., Mol Cell Biol 1999 : In contrast, the inhibition of alphaPKC does not affect the activation of IKKbeta by TNF-alpha
Delhase et al., Science 1999 : In mammalian cells, phosphorylation of two sites at the activation loop of IKKbeta was essential for activation of IKK by tumor necrosis factor and interleukin-1
Aupperle et al., J Immunol 1999 (Arthritis, Rheumatoid) : IKK activity in both RA and osteoarthritis FLS was strongly induced by TNF-alpha and IL-1 in a concentration dependent manner
Nasuhara et al., J Biol Chem 1999 : However, IKK activity was strongly induced by TNF-alpha but not by IL-1beta
Hehner et al., J Immunol 1999 : This study shows that the sesquiterpene lactone parthenolide inhibits a common step in NF-kappa B activation by preventing the TNF-alpha induced induction of I kappa B kinase (IKK) and IKK beta, without affecting the activation of p38 and c-Jun N-terminal kinase ... This study shows that the sesquiterpene lactone parthenolide inhibits a common step in NF-kappa B activation by preventing the TNF-alpha induced induction of I kappa B kinase (IKK) and IKK beta , without affecting the activation of p38 and c-Jun N-terminal kinase
Jeon et al., J Immunol 2000 : Auranofin also blocked IKK activation induced by TNF and PMA/ionomycin, suggesting that the target of auranofin action is common among these diverse signal pathways
Chen et al., J Immunol 2000 : IKK activity was stimulated by both TNF-alpha and TPA, and these effects were inhibited by staurosporine or herbimycin
Kurokouchi et al., J Biol Chem 2001 : Thus, OFF inhibits TNF-alpha induced IKK activation, leading to a decrease in phosphorylation and degradation of inhibitory IkappaBalpha, which in turn results in the decrease of TNF-alpha induced NF-kappaB activation and potentially the transcription of target genes
Schwabe et al., Hepatology 2001 : We analyzed the differential role of I kappa B kinase 1 (IKK1) and I kappa B kinase 2 (IKK2) in tumor necrosis factor alpha (TNF-alpha)- and interleukin-1 beta (IL-1 beta) mediated NF-kappa B activation in primary rat hepatocytes
Goebeler et al., Blood 2001 : However, D609 and the specific p38 inhibitor SB202190 did not affect NiCl ( 2 ) - and TNFalpha induced IKKbeta activation, NF-kappaB DNA binding activity, or transcriptional activity of a Gal4p65 fusion protein
Chen et al., Mol Pharmacol 2001 : TNF-alpha- or C2-ceramide induced COX-2 promoter activity was inhibited by the dominant negative mutant of extracellular signal regulated kinase 2, p38, JNK, IkappaB kinase (IKK)1 , or IKK2 ... IKK activity was stimulated by either TNF-alpha or C2-ceramide, and these effects were inhibited by PD98059 or SB203580
Dikov et al., Cancer Res 2001 : However, although TNF-alpha induced rapid activation of IkappaB kinase (IKK) as expected, this activity was substantially reduced in the presence of VEGF
Tu et al., J Immunol 2001 : TNF-alpha induces activation of inhibitor of NF-kappaB (IkappaB) kinase-beta ( IKK-beta ), a protein kinase that phosphorylates the NF-kappaB inhibitor IkappaB, and thereby targets the latter for degradation via the ubiquitin-proteasome pathway
Devin et al., Mol Cell Biol 2001 : In response to the proinflammatory cytokine tumor necrosis factor (TNF) , IKK is activated after being recruited to the TNF receptor 1 (TNF-R1) complex via TNF receptor associated factor 2 (TRAF2) ... Importantly, IKKgamma is not essential for TNF induced IKK recruitment to TNF-R1, as this occurs efficiently in IKKgamma-deficient cells
Yang et al., Nat Immunol 2001 : The molecular mechanism that underlies IKK activation in response to tumor necrosis factor (TNF) is still unknown
Korn et al., J Biol Chem 2001 : Since oxidants have been implicated in the regulation of NF-kappaB, the focus of the present study was the activation of IKK by tumor necrosis factor alpha (TNFalpha) in the presence or absence of hydrogen peroxide ( H ( 2 ) O ( 2 ) ) ... In contrast, TNFalpha induced IKK activity rapidly and transiently resulting in IkappaBalpha degradation and NF-kappaB activation ... Importantly, in the presence of H ( 2 ) O ( 2 ), the ability of TNFalpha to induce IKK activity was markedly decreased and resulted in prevention of IkappaBalpha degradation and NF-kappaB activation
Yang et al., Mol Pharmacol 2001 : IEC-6 cells pretreated with an extract of green tea polyphenols ( GrTPs ; 0 -- 0.4 mg/ml ) had diminished TNF alpha induced IKK and NF-kappa B activity
Cowling et al., J Biol Chem 2002 : Stimulation with TNF-alpha induced a > 10x increase in I kappa B kinase (IKK) activity that quickly diminished by 20 min. I kappa B-alpha and I kappa B-beta proteins were degraded during this time, and I kappa B-alpha was resynthesized subsequently by NF-kappa B-dependent transcription
Zhang et al., FASEB J 2001 : Furthermore, LA dose-dependently inhibited TNF-alpha induced IkappaB kinase activation , subsequent degradation of IkappaB, the cytoplasmic NF-kappaB inhibitor, and nuclear translocation of NF-kappaB
Mayo et al., J Biol Chem 2002 : PTEN failed to block TNF induced IKK activation , IkappaBalpha degradation, p105 processing, p65 ( RelA ) nuclear translocation, and DNA binding of NF-kappaB
Chen et al., Mol Cell 2002 : TNF induced recruitment and activation of the IKK complex require Cdc37 and Hsp90 ... Geldanamycin ( GA ), an antitumor agent that disrupts the formation of this heterocomplex, prevents TNF induced activation of IKK and NF-kappaB
Jeong et al., Cell Signal 2002 (Calcium Signaling) : These observations demonstrate that the intracellular Ca2+ may play an important role in IgE induced TNF-alpha and IL-6 secretion from mast cells via IKKbeta activation
Zhang et al., J Cell Biochem 2002 (Polyploidy) : Binding of tumor necrosis factor-alpha (TNF-alpha) to its receptor activates IKK complex , which leads to inducement of NF-kappaB activity
Kamata et al., FEBS Lett 2002 : Tumor necrosis factor (TNF) stimulation increased IKK activity within 10 min, and then IKK activity decreased gradually within 30 min in HeLa cells
Algül et al., Am J Physiol Gastrointest Liver Physiol 2002 : Tumor necrosis factor-alpha mediated IKK activation leads to IkappaBalpha and IkappaBbeta degradation
Makris et al., Mol Cell Biol 2002 : Correspondingly, IKK and NF-kappaB activation by TNF-alpha and, to a lesser extent, IL-1 are reduced ... Substitution of two leucines within a C-terminal leucine zipper motif markedly reduced IKK activation by TNF-alpha and IL-1 ... Another point mutation resulting in a cysteine-to-serine substitution within the putative Zn finger motif affected IKK activation by TNF-alpha but not by IL-1
Chen et al., Inflammation 2002 : In addition, EGCG inhibited TNF-alpha mediated activation of IkappaB kinase and subsequent activation of the IkappaB alpha/NF-kappaB pathway
Lang et al., Mol Cell Biol 2003 : Experiments with IKK1 ( -/- ) and IKK2 ( -/- ) double knockout embryonic fibroblasts demonstrate that the IKK complex is essential for TNF-alpha to stimulate phosphorylation on p105 serines 927 and 932
Huang et al., J Biol Chem 2003 : Substitution of these residues with phenylalanines abolished ICAM-1 promoter activity and c-Src dependent phosphorylation of IKKbeta induced by TNF-alpha or TPA
Zernecke et al., FASEB J 2003 : Only at high concentrations, cPG enhanced TNF-alpha induced cell death and inhibited TNF-alpha induced IkappaB-alpha kinase (IKK) activation , IkappaB-alpha degradation, and NF-kappaB/p65 translocation, while promoting AP-1/c-jun phosphorylation
Sakurai et al., J Biol Chem 2003 : Tumor necrosis factor-alpha induced IKK phosphorylation of NF-kappaB p65 on serine 536 is mediated through the TRAF2, TRAF5, and TAK1 signaling pathway
Tang et al., J Biol Chem 2003 : A role for NF-kappaB essential modifier/IkappaB kinase-gamma ( NEMO/IKKgamma ) ubiquitination in the activation of the IkappaB kinase complex by tumor necrosis factor-alpha ... Mutations of the zinc finger are found in patients with hypohidrotic ectodermal dysplasia with immunodeficiency ( HED-ID ) and lead to the impairment of TNF-alpha stimulated IKK phosphorylation and activation ... Thus, the ubiquitination of NEMO mediated by c-IAP1 likely plays an important role in the activation of IKK by TNF-alpha
Kwon et al., Arch Pharm Res 2003 : IL-1beta and TNF-alpha can induce extracellular signal regulated kinase ( ERK ), IKK , IkappaB degradation and NF-kappaB activation
Pantano et al., J Biol Chem 2003 : However, expression of the adaptor protein RIP, which is essential for IKK activation by TNFalpha , was decreased in cells exposed to H2O2, and its chaperone Hsp90 was cleaved
Andreakos et al., Blood 2004 : In contrast, in macrophages neither MyD88, Mal/TIRAP, nor I kappa B kinase 2 (IKK2) are required for NF-kappa B activation or tumor necrosis factor alpha (TNF alpha) , IL-6, or IL-8 production, although Mal/TIRAP is still involved in the production of interferon beta (IFN beta)
Luftig et al., Proc Natl Acad Sci U S A 2004 : In murine embryo fibroblasts ( MEFs ), IKKbeta was essential for LMP1 up-regulation of macrophage inflammatory protein (MIP)-2, TNFalpha , I-TAC, ELC, MIG, and CXCR4 RNAs
Habelhah et al., EMBO J 2004 : Inhibition of Ubc13 expression by RNAi resulted in inhibition of TNFalpha induced TRAF2 translocation and impaired activation of JNK but not of IKK or p38
Yang et al., J Immunol 2004 : The activation of the I-kappaB kinase (IKK) complex by TNF or LPS stimulates phosphorylation and degradation of I-kappaBalpha, leading to the nuclear translocation of NF-kappaB
Broemer et al., Oncogene 2004 (Inflammation...) : Short-time inhibition of Hsp90 resulted in impaired IKK kinase activation by TNFalpha , IL-1beta or phorbolester PMA
Chae et al., Immunopharmacol Immunotoxicol 2004 : TNF-alpha plus IFN-gamma can induce extracellular signal regulated kinase ( ERK ), IKK , IkappaB degradation and NF-kappaB activation
Lee et al., J Biol Chem 2004 : The kinase activity of Rip1 is not required for tumor necrosis factor-alpha induced IkappaB kinase or p38 MAP kinase activation or for the ubiquitination of Rip1 by Traf2 ... TNF-alpha induced Ikk and p38 MAP kinase activation is normal, and the Rip1D138N cells are resistant to TNF-alpha induced cell death, indicating that the kinase activity of Rip1 is not required to mediate its antiapoptotic functions
Lee et al., Exp Cell Res 2004 : TNF-alpha induced activation of IKK was suppressed by HS in human bronchial epithelial cells, and this was associated with the absence of IKK in the immunoprecipitates ... Overexpression of NIK resumed TNF-alpha induced activation of IKK in thermotolerant cells
Zhang et al., J Biol Chem 2004 : At the same time, the binding of AIP1 to TRAF2 inhibits TNF induced IKK-NF-kappaB signaling
Podolin et al., J Pharmacol Exp Ther 2005 (Arthritis, Experimental...) : In the present study, we demonstrate that a novel, potent ( IC ( 50 ) = 17.9 nM ), and selective inhibitor of human IKK-2 , 2- [ ( aminocarbonyl ) amino ] -5- ( 4-fluorophenyl ) -3-thiophenecarboxamide ( TPCA-1 ), inhibits lipopolysaccharide induced human monocyte production of TNF-alpha , IL-6, and IL-8 with an IC ( 50 ) = 170 to 320 nM
Panopoulos et al., J Biol Chem 2005 (Inflammation) : Here we show that l-mimosine, a toxic non-protein amino acid that has been shown to reduce serum TNFalpha levels and affect inflammatory responses, specifically inhibits TNF induced IKK but not JNK in a cell type-specific manner
Syrovets et al., J Immunol 2005 : The LPS triggered induction of TNF-alpha in monocytes is dependent on IKK activity, as confirmed by IKK-specific antisense oligodeoxynucleotides
Gupta et al., Cell Death Differ 2005 : In this study, we have compared TNF-alpha induced activation of NF-kappaB, phosphorylation of IkappaBalpha, and the expression of IKKbeta between lymphocytes from young and aged humans
Peng et al., J Leukoc Biol 2005 : Here, we demonstrated that inhibition of inhibitor of kappaB (IkappaB) kinase ( IKK ) by a peptide IKK inhibitor or by four individual chemical IKK inhibitors including 15-deoxy-prostaglandin J ( 2 ), BMS-345541, SC-514, or sulindac significantly blocked IgE + trinitrophenyl ( TNP ) -induced TNF production by mouse bone marrow derived MC ( BMMC )
Hall et al., Am J Physiol Heart Circ Physiol 2005 : Pharmacological inhibition of IKK-beta reduced LPS induced TNF-alpha production 38-fold, TNF-alpha mRNA levels 6-fold, and IkappaB-alpha phosphorylation 5-fold and degraded IkappaB-alpha 2-fold and p65 phosphorylation 6-fold ... Overexpression of dominant negative p65 reduced TNF-alpha production 3.5-fold, whereas overexpression of dominant negative IKK-beta reduced LPS induced TNF-alpha production 2-fold and p65 phosphorylation 2-fold
Cusson-Hermance et al., J Biol Chem 2005 : Rip1 is required for IkappaB kinase activation in response to tumor necrosis factor alpha (TNF-alpha) and has been implicated in the Toll-like receptor 3 (TLR3) response to double stranded RNA
Kray et al., J Biol Chem 2005 (Inflammation) : This pathway is initiated by TNF dependent phosphorylation of T loop serines in IKKbeta , which greatly stimulates IkappaB kinase activity
Werner et al., Science 2005 : Although tumor necrosis factor-alpha (TNFalpha) induced IKK activity was rapidly attenuated by negative feedback, lipopolysaccharide (LPS) signaling and LPS-specific gene expression programs were dependent on a cytokine mediated positive feedback mechanism
Aggarwal et al., Mol Pharmacol 2006 (Neoplasm Metastasis) : Curcumin also inhibited TNF induced Akt activation and its association with IKK
Chang et al., J Dent Res 2005 : We found that both TNF and LPS activated the I-kappa B kinase complex (IKK) in DPSCs to induce the phosphorylation and degradation of IkappaBalpha, resulting in the nuclear translocation of NF-kappaB
Xie et al., Toxicological sciences : an official journal of the Society of Toxicology 2006 : The activity of tumor necrosis factor-alpha induced inhibitor of kappa B (IkappaB) kinase alpha was also inhibited by Cd
Li et al., Acta Pharmacol Sin 2006 (Pulmonary Disease, Chronic Obstructive) : NAC inhibited the phosphorylation of IKKbeta, IKK alpha, and IkappaB alpha induced by TNF-a , but had no effect on the phosphorylation of IKKbeta, IKK alpha and IkappaB alpha induced by IL-1 ... NAC can inhibit the processes upstream of IKK activation induced by TNF- alpha , which results in the decline of NF-kappaB activity
Wen et al., J Pharmacol Exp Ther 2006 : For the first time, we have demonstrated that in human fibroblast-like synoviocytes, TNFalpha- or interleukin (IL)-1beta induced monocyte chemoattractant protein-1 regulated on activation, normal T cell expressed and secreted and production is IKKbeta dependent
Ea et al., Mol Cell 2006 : Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO
Hai et al., J Virol 2006 : Similarly, IKKgamma-delta mediates IKK kinase activity and downstream NF-kappaB dependent transcription in response to tumor necrosis factor (TNF) and the NF-kappaB inducing kinase-IKKalpha signaling pathway
Higashimoto et al., Cytokine 2006 (Chromosome Aberrations) : TNFalpha induces chromosomal abnormalities independent of ROS through IKK , JNK, p38 and caspase pathways ... In cells progressing through S-phase, TNFalpha activation of IKK , JNK, and p38 is significantly reduced
Park et al., Carcinogenesis 2007 (Neoplasms) : PMA selectively causes the degradation of IkappaB kinases ( IKKs ) including IKK-gamma and IKK-beta, and subsequent inhibition of tumor necrosis factor (TNF) induced IKK and NF-kappaB activation in human colon cancer cell line HCT-116, but not in other gastrointestinal tract cells ... The use of Ro-318220 and GO-6983, general PKC inhibitors as well as MG-132, a proteasome-specific inhibitor, abrogated PMA induced degradation of IKK-gamma and recovered the activation of IKK by TNF , suggesting that IKK complex is predominantly degraded by the proteasome pathway in a PKC dependent manner
Reynaert et al., Proc Natl Acad Sci U S A 2006 : Conversely, GRX1 knockdown sensitizes cells to oxidative inactivation of IKK-beta and dampens TNF-alpha induced IKK and NF-kappaB activation
Dajani et al., Am J Physiol Gastrointest Liver Physiol 2007 (Endotoxemia...) : Using TNF-alpha knockout mice and hepatic-specific inhibition of IKKbeta , we demonstrate that the status of TNF-alpha and NF-kappaB balances necrotic and apoptotic fates of hepatocytes in the setting of endotoxemia
Widera et al., BMC neuroscience 2006 : TNF mediated activation of IKK-beta resulted in activation of NF-kappaB and was followed by up-regulation of the bona-fide target gene cyclin D1
Sethi et al., Blood 2007 (Neoplasm Invasiveness...) : Recent studies indicate that TNF induced IKK activation requires activation of TAK1, and we indeed found that celastrol inhibited the TAK1 induced NF-kappaB activation
Besse et al., J Biol Chem 2007 : A green fluorescent protein fusion protein containing the last 100 residues of TAK1 ( TAK1-C100 ) abolished the interaction of endogenous TAB2/TAB3 with TAK1, the phosphorylation of TAK1, and prevented the activation of IKK and MAPK induced by IL-1, TNF , and RANKL
Besse et al., Biochem Biophys Res Commun 2007 : Stable expression of TRIP or a RING mutant did not affect IKK activation induced by TNF or IL-1 and had no affect on TNF induced apoptosis
Lou et al., J Biol Chem 2007 : With moderate GSH depletion ( approximately 50 % ), the down-regulation is IkappaB kinase (IKK) independent and likely acts on NF-kappaB transcriptional activity because TNF induced IKK activation , IkappaBalpha phosphorylation and degradation, NF-kappaB nuclear translocation, NF-kappaB DNA binding in vitro, and NF-kappaB subunit RelA ( p65 ) recruitment to kappaB sites of target gene promoters all appear unaltered
Wu et al., Am J Physiol Endocrinol Metab 2007 : The present study demonstrates that the globular domain of adiponectin ( gAd ) potently suppresses the activation of IKKbeta by either TNFalpha or high glucose in human umbilical vein endothelial cells and ameliorates the associated loss of IkappaBalpha protein ... Interestingly, activation of AMP kinase was substantially more effective than cAMP signaling in suppressing high glucose induced IKKbeta activity, whereas both pathways were comparably active in suppressing the TNFalpha induced increase in IKKbeta ... Both cAMP/protein kinase A signaling and activation of the AMP kinase pathway played a role in the suppression by gAd of TNFalpha- and high glucose mediated IKKbeta activation
Diessenbacher et al., J Invest Dermatol 2008 : However, when induction of NF-kappaB was inhibited with a kinase dead IKK2 mutant ( IKK2-KD ), TNF- but not TRAIL induced apoptosis was dramatically enhanced
Ahmad et al., Nat Cell Biol 2007 : Studies in non-malignant epithelial cells show that MUC1 is recruited to the TNF-R1 complex and interacts with IKKbeta-IKKgamma in response to TNFalpha stimulation
Herscovitch et al., Biochem Biophys Res Commun 2008 : We also show that pretreatment with H ( 2 ) O ( 2 ) decreases TNFalpha induced IKK activity in NEMO reconstituted cells, and that TNFalpha has a diminished ability to activate NF-kappaB DNA binding in cells reconstituted with NEMO mutant C54/347A
Okayasu et al., Life Sci 2008 : We demonstrated that TNFalpha stimulates IkappaB-alpha phosphorylation through induction of IKK activity, and that fenofibrate inhibits IKK activity and TNFalpha induced IkappaB-alpha phosphorylation
MacPartlin et al., J Biol Chem 2008 : Activation of IKKbeta by gamma radiation or tumor necrosis factor-alpha led to increased TAp63gamma protein levels in cells
Dan et al., J Immunol 2008 : In MCF7 cells, TNF does not activate Akt and requires IKKbeta to activate mTOR
Huang et al., Int J Cardiol 2009 (Atherosclerosis) : Metformin inhibits TNF-alpha induced IkappaB kinase phosphorylation, IkappaB-alpha degradation and IL-6 production in endothelial cells through PI3K dependent AMPK phosphorylation ... Pre-treatment with metformin ( 100-1000 micromol/L ) also inhibited TNF-alpha induced IL-6 production, phosphorylation of IkappaB kinase (IKK) alpha/beta and IkappaB-alpha degradation
Funakoshi-Tago et al., Biochem Pharmacol 2008 : Here, we found that Celecoxib potently inhibited TNFalpha induced transcriptional activity and DNA binding activity of NF-kappaB ; however, Celecoxib had no effect on TNFalpha induced IKK activation and degradation of IkappaBalpha and IkappaBbeta, suggesting that it inhibited NF-kappaB activation via suppressing downstream of IKK activation and IkappaBs degradation
Sun et al., Cell Signal 2009 : PPM1A and PPM1B act as IKKbeta phosphatases to terminate TNFalpha induced IKKbeta-NF-kappaB activation ... PPM1A and PPM1B associate with the phosphorylated form of IKKbeta, and the interaction between PPM1A/PPM1B and IKKbeta is induced by TNFalpha in a transient fashion in the cells ... Furthermore, knockdown of PPM1A and PPM1B expression enhances TNFalpha induced IKKbeta phosphorylation, NF-kappaB nuclear translocation and NF-kappaB dependent gene expression
Higashimoto et al., J Biol Chem 2008 : Expressing a constitutively active Plk1 in mammalian cells reduced tumor necrosis factor (TNF) induced IKK activation, resulting in decreased phosphorylation of endogenous IkappaBalpha and reduced NF-kappaB activation ... To activate endogenous Plk1, cells were treated with nocodazole, which reduced TNF induced IKK activation, and increased the phosphorylation of gammaBD ... Knocking down Plk1 in mammalian cells restored TNF induced IKK activation in nocodazole treated cells ... Moreover, we identify Plk1 as a gammaBD kinase, which negatively regulates TNF induced IKK activation and cyclin D1 expression, thereby affecting cell cycle regulation
Blackwell et al., Mol Cell Biol 2009 (Lymphoma) : Although TRAF2 phosphorylation had a minimal effect on the TNF-alpha induced rapid and transient IKK activation , it was essential for secondary and prolonged IKK activation ... These results unveil a new, finely tuned mechanism for TNF-alpha induced IKK activation modulated by TRAF2 phosphorylation and suggest that TRAF2 phosphorylation contributes to elevated levels of basal NF-kappaB activity in certain human cancers
Zhang et al., Cancer Res 2008 (Pancreatic Neoplasms) : Therefore, inhibition of TNFalpha induced IKK activity with specific IKK inhibitor represents an attractive strategy to treat cancer patients ... This study reveals IKI-1 as a potent small molecule inhibitor of IKKalpha and IKKbeta, which effectively blocked TNFalpha mediated IKK activation and subsequent NF-kappaB activity
Funakoshi-Tago et al., Cytokine 2009 : Compared to those observed in wild-type MEFs, TNFalpha induced IkappaB kinase (IKK) activation and IkappaBalpha degradation were enhanced in TRAF6-deficient MEFs ... Moreover, the reintroduction of exogenous TRAF6 into TRAF6-deficient MEFs clearly suppressed TNFalpha induced IKK activation, NF-kappaB activation and subsequent cytokine expression ... In contrast, both the deletion mutant ( DeltaN ) and the point mutant ( C70A ) of TRAF6, which is defective in its ubiquitin ligase activity, failed to repress TNFalpha induced IKK activation, NF-kappaB activation and cytokine production
Li et al., Mol Cell 2009 : The combined data reveal that phosphorylation of TRAF2 plays a critical role in TNF signaling by directing the IKK complex to the membrane, promoting TRAF2 K63 linked ubiquitination, and positioning the IKKalpha and IKKbeta chains with the TAK1/TAB kinase
Dhingra et al., Cardiovasc Res 2009 : Inhibition of ERK 1/2 MAPK with PD98059 attenuated the protective role of IL-10 against TNF-alpha induced activation of IKK and NF kappaB as well as cardiomyocyte apoptosis
Ding et al., Curr Cancer Drug Targets 2009 : Further studies show that neither overexpression of IKKbeta-KM, a kinase inactive mutant of IKKbeta , nor the ectopic expression of a dominant negative mutant of NFAT could inhibit the TNF-alpha induction by nickel exposure
Kawauchi et al., Proc Natl Acad Sci U S A 2009 : We also found that high glucose induced the O-GlcNAcylation of IKKbeta and sustained the TNFalpha dependent IKKbeta activity
Thomas et al., Cancer Res 2009 : Although many serine/threonine kinases have been implicated in TNFalpha induced IKK activation and NF-kappaB dependent gene expression, most of them do not directly activate IKK ... These results reveal a new level of complexity in TNFalpha induced IKK activation modulated by TRAF2 phosphorylation and suggest that TRAF2 phosphorylation is one of the events that are responsible for elevated basal NF-kappaB activity in certain human cancers
Zhang et al., J Mol Biol 2009 : TRAF2 suppresses basal IKK activity in resting cells and TNFalpha can activate IKK in TRAF2 and TRAF5 double knockout cells ... Although TNFalpha induced receptor interacting protein 1 ubiquitination is indeed impaired in T2/5 DKO cells, TNFalpha stimulation further increases IKK activity in these cells, resulting in significantly elevated expression of NF-kappaB target genes to a level higher than that in wild-type cells ... Inhibition of NIK in T2/5 DKO cells attenuates basal IKK activity and restores robust TNFalpha induced IKK activation to a level comparable with that seen in wild-type cells ... This suggests that TNFalpha can activate IKK in the absence of TRAF2 and TRAF5 expression and receptor interacting protein 1 ubiquitination
Tsutsui et al., Bioorg Med Chem Lett 2009 (Inflammation) : Consistent with these results, peperomin E and 2,6-didehydropeperomin B blocked the TNF-alpha induced activation of IkappaB kinase , while they had no direct effect on the IkappaB kinase activity
Ha et al., Biochemistry 2009 : TPCK inhibited tumor necrosis factor-alpha induced IKK activation and directly blocked IKK activity in vitro
Funakoshi-Tago et al., Mol Pharmacol 2009 : Whereas licochalcone A had no effect on the recruitment of receptor interacting protein 1 and IkappaB kinase beta (IKKbeta) to TNF receptor I by TNF-alpha, it significantly inhibited TNF-alpha induced IkappaB kinase complex (IKK) activation and inhibitor of nuclear factor-kappaB degradation ... In contrast, a structurally related compound, echinatin, failed to inhibit TNF-alpha induced IKK activation and NF-kappaB activation, suggesting that the 1,1-dimethy-2-propenyl group in licochalcone A is important for the inhibition of NF-kappaB
Kuo et al., Biochem Biophys Res Commun 2009 (Breast Neoplasms) : TNFalpha induces HIF-1alpha expression through activation of IKKbeta
Liu et al., Proc Natl Acad Sci U S A 2009 : Neither JNK1 activation by IL-1beta or UV nor TNF-alpha induced activation of p38, ERK, or IkappaB kinase complex is affected by the loss of Miz1
Xu et al., Mol Cell 2009 : A ubiquitin replacement strategy in human cells reveals distinct mechanisms of IKK activation by TNFalpha and IL-1beta ... We demonstrate that K63 of ubiquitin and the catalytic activity of Ubc13, an E2 that catalyzes K63 polyubiquitination, are required for IKK activation by IL-1beta, but surprisingly, not by TNFalpha ... We further show that IKK activation by TNFalpha requires Ubc5, which functions with the E3 cIAP1 to catalyze polyubiquitination of RIP1 not restricted to K63 of ubiquitin
Gossye et al., Arthritis Rheum 2009 (Arthritis, Rheumatoid) : In sharp contrast, DEX did not affect TNFalpha induced IKK phosphorylation, IkappaBalpha degradation, p65 nuclear translocation, or MAPK activation in RA FLS
Zhang et al., J Mol Biol 2010 : The TRAF2 RING domain mediated polyubiquitination of RIP1 is believed to be essential for TNFalpha induced IKK activation , and the RING-domain deleted TRAF2 ( TRAF2-DeltaR ) has been widely used as a dominant negative in transient overexpression systems to block TNFalpha induced JNK and IKK activation ... Here, we report that stable expression of TRAF2-DeltaR at a physiological level in TRAF2 and TRAF5 double knockout ( TRAF2/5 DKO ) cells almost completely restores normal TNFalpha induced IKK activation, but not RIP1 polyubiquitination ... These data suggest that ( i ) the TRAF2 RING domain plays a critical role in inhibiting cell death induced by TNFalpha and is essential for suppressing the noncanonical nuclear factor kappaB pathway in unstimulated cells ; ( ii ) RIP1 polyubiquitination is not essential for TNFalpha induced IKK activation; and (iii) prolonged JNK activation has no obligate role in TNFalpha induced cell death
Tseng et al., J Cell Physiol 2010 : Stimulation of myoblasts with TNF-alpha activated IkappaB kinase alpha/beta ( IKKalpha/beta ), IkappaBalpha phosphorylation, p65 phosphorylation, and kappaB-luciferase activity
Funakoshi-Tago et al., Int Immunopharmacol 2010 (Edema) : Whereas Licochalcone A potently inhibited TNFalpha induced IKK activation, IkappaBalpha degradation, nuclear localization of NF-kappaB and its DNA binding activity, no inhibitory effect was observed by reduced Licochalcone A
Zhang et al., Mol Biol Cell 2010 : We describe a new regulatory mechanism for PLK1 : PLK1 negatively regulates TNF induced IKK activation by inhibiting the ubiquitination of NEMO
Rehman et al., Int J Oral Sci 2009 (Carcinoma, Squamous Cell...) : We found that loss of components of the CBM complex in HNSCC can inhibit SDF-1 alpha induced phosphorylation and degradation of IkappaBalpha, while TNF alpha induced IKK activation remains unchanged
Song et al., J Pharmacol Sci 2010 (MAP Kinase Signaling System) : The results showed that ruscogenin significantly suppressed p65 phosphorylation, IkappaB-alpha phosphorylation and degradation, and inhibited IkappaB kinase alpha (IKKalpha) and IKKbeta activation induced by TNF-alpha
Li et al., J Biol Chem 2011 (Diabetic Retinopathy...) : Conversely, overexpression of spliced XBP1 attenuated TNF-a induced phosphorylation of IKK , I?Ba, and NF-?B p65, accompanied by decreased NF-?B activity and reduced adhesion molecule expression
Anand et al., Biochem Pharmacol 2011 : For inhibition of TNF induced IKK activation, DBA was most active
Cheng et al., J Surg Res 2012 (Reperfusion Injury) : Pretreatment with NBD peptides significantly improved liver function, attenuating liver parenchymal cell damage, apoptosis by down regulating TNF-a level, inhibiting IKK complex phosphorylation, I?Ba degradation, and NF-?B transcriptional activity, but had no effect in normal condition
Balwani et al., PloS one 2012 : We observed that MPTAG does not directly inhibit IKK-ß but prevents TNF-a induced activation of IKK-ß by blocking its association with Akt and thereby inhibits NF-?B activation
Kim et al., Am J Physiol Gastrointest Liver Physiol 2013 (Disease Models, Animal...) : Pretreatment with GG-52 suppressed TNF-a induced activation of I?B kinase ( IKK ) and NF-?B signaling in MKN-45 cells
Roy et al., J Biochem 2013 : Inhibition of protein kinase C ( PKC ) -a activity by Go6976 and PKC-a siRNA prevented TNF-a induced IKK activity, I?B-a phosphorylation/degradation and NF-?B activation
Maubach et al., Int J Cancer 2013 (Helicobacter Infections) : Our results show that CAMKII and calmodulin contribute to IKK complex activation and thus to the induction of NF-?B in response to H. pylori infection, but not in response to TNF-a
Puckett et al., Mol Cell Biol 2013 : IKK can be activated by growth factor stimulation or tumor necrosis factor alpha engagement
Woronicz et al., Science 1997 : The activity of IKK-beta was stimulated by tumor necrosis factor and interleukin-1 treatment
Geleziunas et al., Mol Cell Biol 1998 (Cell Transformation, Viral...) : Our studies now demonstrate that HTLV-1 Tax activates the recently identified cellular kinases IkappaB kinase alpha (IKKalpha) and IKKbeta , which normally phosphorylate IkappaB alpha on both of its N-terminal regulatory serines in response to tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) stimulation
O'Connell et al., J Biol Chem 1998 : Recently, we have reported that the tumor necrosis factor and interleukin 1 signaling pathways activate two kinases, IKK1 and IKK2 ... Recently, we have reported that the tumor necrosis factor and interleukin 1 signaling pathways activate two kinases, IKK1 and IKK2
Nemoto et al., Mol Cell Biol 1998 : MEKK1 is activated by tumor necrosis factor alpha (TNF-alpha) and interleukin-1 and can potentiate the stimulatory effect of TNF-alpha on IKK and NF-kappaB activation