◀ Back to TNF
IKBKG — TNF
Pathways - manually collected, often from reviews:
-
OpenBEL Selventa BEL large corpus:
IKBKG
→
TNF
(increases)
Ogura et al., J Biol Chem 2001*
Evidence: The TNF-alpha induced activation of NF-kB is completely inhibited by the presence of dominant negative forms of IkB-alpha, IKK-alpha, IKK-beta, IKK-gamma and RIP, where in control cells it is almost 100%.
-
OpenBEL Selventa BEL large corpus:
TNF
→
IKBKG
(increases)
Chandrasekar et al., J Biol Chem 2004*
Evidence: The cells transiently transfected with IKK-Gamma small interfering RNA expressing vector, significantly attenuated IL-18 induced IL-1beta and TNF-alpha secretion. The level of secretion is almost half compared to cells induced by IL-18 alone
-
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
—
IKBKG
(physical association, affinity chromatography technology)
Tokunaga et al., EMBO J 2012
-
IRef Biogrid Interaction:
TNF
—
IKBKG
(physical association, affinity chromatography technology)
Verhelst et al., EMBO J 2012
-
IRef Biogrid Interaction:
TNF
—
IKBKG
(physical association, affinity chromatography technology)
Haas et al., Mol Cell 2009
-
IRef Biogrid Interaction:
TNF
—
IKBKG
(physical association, affinity chromatography technology)
Ea et al., Mol Cell 2006
-
IRef Intact Interaction:
TNF
—
IKBKG
(physical association, anti tag coimmunoprecipitation)
Boisson et al., Nat Immunol 2012
-
IRef Intact Interaction:
Complex of SHARPIN-IKBKG-RNF31-TNFAIP3-TNF-RBCK1
(association, anti tag coimmunoprecipitation)
Verhelst et al., EMBO J 2012
Text-mined interactions from Literome
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
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
Krappmann et al., J Biol Chem 2000
:
Overexpression of either
IKK gamma or IKAP
blocked tumor necrosis factor alpha induction of an NF-kappa B-dependent reporter construct, but IKAP in addition affected several NF-kappa B-independent promoters
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
Chen et al., Mol Pharmacol 2001
:
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
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 ... Using TRAF2 ( -/- ) cells, we demonstrated that the
TNF induced interaction between
IKKgamma and the death domain kinase RIP is TRAF2 dependent and that one possible function of this interaction is to stabilize the IKK complex when it interacts with TRAF2
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
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
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
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
Carter et al., J Biol Chem 2003
:
We now demonstrate that
TNF induced phosphorylation of
IKKgamma is blocked in cells deficient for IKKbeta but not IKKalpha
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
:
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
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
:
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
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
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
Nenci et al., Hum Mol Genet 2006
(Disease Models, Animal...) :
Skin lesion development in a mouse model of incontinentia pigmenti is triggered by
NEMO deficiency in epidermal keratinocytes and
requires TNF signaling
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
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
Feng et al., Blood 2007
(Bone Resorption...) :
SDX-308 effectively suppressed
TNF-alpha induced
IKK-gamma and IkappaB-alpha phosphorylation and degradation and subsequent NF-kappaB activation in human multiple myeloma cells
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
Hong et al., J Biol Chem 2007
:
Interestingly, peptides spanning CCR2 and/or LZ disrupt IKKgamma-Tax and
IKKgamma-PP2A interactions and potently
inhibit NF-kappaB activation by Tax and
tumor necrosis factor-alpha
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
Zhu et al., Curr Biol 2007
(Glaucoma) :
Optineurin negatively
regulates TNFalpha- induced NF-kappaB activation by competing with
NEMO for ubiquitinated RIP
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
Shifera et al., Mol Cell Biochem 2008
:
Our results indicate that
IKK gamma regulates
TNF alpha signaling by coordinating cell responses mediated by the AP-1 and NF-kappa B pathways
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
Szijártó et al., Magy Seb 2008
(Reperfusion Injury) :
After 45 and 60 minutes,
IP + I-R caused a significant decline in the
TNF-alpha levels
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
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
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
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
:
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
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
Yiu et al., Cell Biochem Funct 2010
:
Transcriptional
regulation of
IER3IP1 gene by
tumor necrosis factor-alpha and Sp family proteins
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
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
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
Verhelst et al., EMBO J 2012
:
Both A20 and ZF7 can form a complex with NEMO and LUBAC, and are able to prevent the
TNF induced binding of
NEMO to LUBAC ... We thus propose a model in which A20 inhibits TNF- and LUBAC induced NF-?B signalling by binding to linear polyubiquitin chains via its seventh zinc finger, which prevents the
TNF induced interaction between LUBAC and
NEMO
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
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
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