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RELA — TRAF2
Pathways - manually collected, often from reviews:
Text-mined interactions from Literome
Puls et al., J Cell Sci 1999
(Inflammation) :
Using LMP1 mutants, we show that activation of Cdc42 and
JNK/NF(kappa)B occur through distinct pathways and that Cdc42 activation is
independent of LMP1 's interaction with TRADD and
TRAF proteins
Chin et al., Mol Cell Biol 1999
(MAP Kinase Signaling System) :
We previously described the involvement of a TRAF interacting molecule, TRAF associated NF-kappaB activator ( TANK ), in
TRAF2 mediated
NF-kappaB activation
Carpentier et al., FEBS Lett 1999
:
Interestingly, overexpression of TRAF1 in HEK293T completely prevented
NF-kappaB activation
induced by TNF, IL-1, or overexpression of
TRAF2 or TRAF6
Pomerantz et al., EMBO J 1999
:
However, TANK also displays the ability to stimulate
TRAF mediated
NF-kappaB activation ... The TBK1-TANK-TRAF2 signaling complex functions upstream of NIK and the IKK complex and represents an alternative to the receptor signaling complex for
TRAF mediated activation of
NF-kappaB
Leonardi et al., J Biol Chem 2000
:
TRAF2 is required for TNF induced activation of c-Jun N-terminal kinase/stress activated protein kinase ( JNK/SAPK ), and
TRAF2 can also
mediate activation of
NF-kappaB ... Overexpressed Filamin inhibits
TRAF2 induced activation of JNK/SAPK and of
NF-kappaB
Ivanov et al., Oncogene 2000
(Melanoma) :
Conversely, forced expression of the dominant negative form of
TRAF2 or GCK in late-stage melanoma cells
reduced NF-kappaB activity and decreased Fas expression, resulting in a lower degree of UV-induced, Fas mediated cell death
Nomura et al., Genes Cells 2000
:
NF-kappaB activation by IKK-i is significantly
blocked by coexpression of the N-terminal domain of
I-TRAF , dominant negative TRAF2, and dominant negative NIK and IKK-beta
Zapata et al., J Biol Chem 2000
:
In contrast,
TRAF2 mediated
NFkappaB induction was partially inhibited by DTRAF1
Devin et al., Immunity 2000
:
To understand the mechanism by which RIP and
TRAF2 regulate TNF induced activation of the transcription factor
NF-kappaB , we investigated their respective roles in TNF-R1 mediated IKK activation using both RIP-/- and TRAF2-/- fibroblasts
Takaori-Kondo et al., Biochem Biophys Res Commun 2000
:
TRAF3 blocked OX40-,
TRAF2 induced NF-kappaB activation, but not NIK- and IKKalpha induced
NF-kappaB activation , indicating that TRAF3 blocks the pathway between TRAF2 and NIK
Chainy et al., Oncogene 2000
:
Suppression of IkappaBalpha phosphorylation and
NF-kappaB reporter gene expression
induced by
TRAF2 and NIK, suggests that anethole acts on IkappaBalpha kinase
Pereno et al., Oncogene 2000
(Melanoma) :
Since
TRAF2 activates the transcription factor
NF-kappaB , IL-15 through IL-15Ralpha, could have a role in the control of this pathway
Zapata et al., J Biol Chem 2001
:
Analysis of various MUL and USP7 mutants by transient transfection assays indicated that the TDs of these proteins are necessary and sufficient for suppressing
NF-kappaB induction by
TRAF2 and TRAF6 as well as certain TRAF binding TNF family receptors
Seitz et al., J Biol Chem 2001
:
Overexpression of the icp75TNFR cDNA results in TNF induced activation of
NFkappaB in a
TNF receptor associated factor 2 (TRAF2) dependent manner
Chung et al., Biochem Biophys Res Commun 2001
:
Expression of dominant negative form of TRAF2 inhibits the synergistic effects of HCV core protein on NF-kappaB activation, suggesting that HCV core protein potentiates
NF-kappaB activation through
TRAF2
Van Huffel et al., J Biol Chem 2001
:
The latter also inhibits
NF-kappaB activation
induced by overexpression of receptor interacting protein or
TNF receptor associated factor 2
Knecht et al., Oncology 2001
(Cell Transformation, Neoplastic...) :
TRAF2 mediated
NF-kappaB activation , AP-1 induction and JAK3/STAT activation may result in sustained proliferation leading to lymphoma
Chandel et al., J Biol Chem 2001
:
Consistent with its anti-apoptotic function, Bcl-x ( L ) interfered with
TRAF mediated ROS generation but not
NF-kappaB activation
Xia et al., J Biol Chem 2002
:
We identified a TRAF2 binding motif of SphK that mediated the interaction between TRAF2 and SphK resulting in the activation of the enzyme, which in turn is required for
TRAF2 mediated activation of
NF-kappa B but not JNK
Jang et al., Mol Cells 2001
:
Overexpression of LRR-1 suppressed the activation of
NF-KB induced by 4-1BB or TNF receptor associated factor
(TRAF) 2
Horie et al., Oncogene 2002
(Hodgkin Disease) :
We report that in H-RS cells overexpression of CD30 leads to self-aggregation, recruitment of
TRAF2 and TRAF5, and
NF-kappaB activation , independent of CD30 ligand
Leonardi et al., Endocrinology 2002
:
Dominant negative
TNF receptor associated factor 2 (TRAF2) inhibited activation of
NF-kappa B , which was also inhibited in embryonic fibroblasts derived from TRAF2 ( -/- ) mice, respect to their normal counterpart
Naito et al., Proc Natl Acad Sci U S A 2002
(Ectodermal Dysplasia) :
Furthermore,
TRAF6 is
essential for the XEDAR mediated
NFkappaB activation
Wu et al., Gene Expr 2002
:
In addition, ZAS3 associates with a
TNF receptor associated factor to
inhibit NF-kappaB- and JNK/ SAPK mediated signaling of TNF-alpha
Lee et al., J Biochem Mol Biol 2002
:
The inhibitory effect of the TAK1 mutant on RANK- and
TRAF induced
NF-kappaB activation was also observed, but less efficiently
Costanzo et al., J Cell Physiol 2003
:
However, NFkappaB stimulation by AII differs from that of TNF-alpha since a
TNF-receptor associated factor 2 ( TRAF-2 ) dominant negative mutant does not
prevent AII mediated
NFkappaB activation
Henkler et al., J Biol Chem 2003
:
The
role of tumor necrosis factor
(TNF) receptor associated factor ( TRAF)-1 in
NF-kappaB activation by various members of the TNF receptor family is not well understood, and conflicting data have been published ... Here, we show that TRAF1 differentially affects
TRAF2 recruitment and
activation of
NF-kappaB by members of the TNF receptor family
Bin et al., J Biol Chem 2003
:
Moreover, TIRP mediated
NF-kappaB activation is
inhibited by dominant negative mutants of IRAK, IRAK-2,
TRAF6 , and IKKbeta
Park et al., J Biol Chem 2003
(Hepatitis C) :
Both TNF-alpha- and TRAF2 mediated
nuclear factor-kappaB (NF-kappaB) activations were
inhibited by
NS5A-TRAF2 interaction
Sakon et al., EMBO J 2003
:
Importantly, TNF does not induce ROS accumulation or prolonged MAPK activation in wild-type MEFs, indicating that
TRAF mediated
NF-kappaB activation normally suppresses the TNF induced ROS accumulation that subsequently induces prolonged MAPK activation and necrotic cell death
Fotin-Mleczek et al., J Biol Chem 2004
:
Accordingly,
TRAF1 inhibited CD40 dependent but not TNF-R1 dependent
NF-kappaB activation
Takada et al., J Biol Chem 2004
:
NF-kappaB reporter activity
induced by TNF receptor 1, TNF receptor associated death domain,
TNF receptor associated factor-2 , NF-kappaB inducing kinase, and IkappaBalpha kinase, were all blocked by flavopiridol but not that activated by p65
Habelhah et al., EMBO J 2004
:
Ubiquitination and translocation of
TRAF2 is
required for activation of JNK but not of p38 or
NF-kappaB ... These findings demonstrate that the TRAF2 RING is required for Ubc13 dependent ubiquitination, resulting in translocation of
TRAF2 to an insoluble fraction and
activation of JNK, but not of p38 or
NF-kappaB
Gotoh et al., Biochem Biophys Res Commun 2004
:
Furthermore, the reduced expression of PKN1 by RNA interference ( RNAi ) down-regulated
TRAF2 induced
NF-kappaB activation in HEK293T cells
Hentze et al., Hepatology 2004
:
CPT treatment completely abrogated the TNF induced
NF-kappa B activation, and mRNA expression of the antiapoptotic factors
TNF-receptor associated factor 2 , FLICE-inhibitory protein, and X-linked inhibitor of apoptosis protein was also
inhibited by CPT. The caspase inhibitors benzyloxycarbonyl-Val-Ala-Asp- ( OMe ) -fluoromethylketone ( zVAD-fmk ) and benzyloxycarbonyl-Asp ( OMe ) -Glu ( OMe ) -Val-Asp ( OMe ) -chloromethylketone ( zDEVD-fmk ), as well as depletion of intracellular ATP by fructose prevented CPT/TNF induced apoptosis
Hu et al., J Biol Chem 2004
:
TNAP specifically inhibits
NF-kappaB activation
induced by tumor necrosis factor (TNF)-alpha, TNF receptor 1, TRADD, RIP,
TRAF2 , and NIK but does not affect IKK1- and IKK2 mediated NF-kappaB activation
Zhang et al., J Biol Chem 2004
:
At the same time, the binding of AIP1 to
TRAF2 inhibits TNF induced
IKK-NF-kappaB signaling
Aggarwal et al., J Immunol 2004
(Melanoma) :
Mda-7 transfection also potentiated
NF-kappaB reporter activation
induced by TNF receptor associated death domain and
TNF receptor associated factor-2
Grech et al., Immunity 2004
:
To examine the
role of the TNF-R superfamily signaling protein
TRAF2 in mature B cell development and
NF-kappaB activation, conditionally TRAF2-deficient mice were produced
Fan et al., Oncogene 2005
:
HGF/SF induced the expression of several known NF-kappaB target genes ( cIAP-1 ( cellular inhibitor of apoptosis-1 ), cIAP-2, and
TRAF-2 ( TNF receptor associated factor-2 ) ) in an
NF-kappaB dependent manner ; HGF/SF blocked the inhibition of expression of these genes by ADR
Kim et al., Mol Cell Biol 2005
:
However, LIGHT induced
NF-kappaB and JNK activation can be
restored by ectopic expression of
TRAF2 in TRAF2-/- cells
Esparza et al., J Immunol 2005
:
GITR induced activation of NF-kappaB is blocked by A20, an NF-kappaB-inducible protein that interacts with TRAFs and functions in a negative feedback mechanism downstream of other TNFRs. Interestingly, in contrast with its effects on signaling triggered by other TNFRs, our functional studies revealed that
TRAF2 plays a novel inhibitory role in GITR triggered
NF-kappaB activation
Min et al., J Immunol 2005
:
TNF related activation induced cytokine enhances leukocyte adhesiveness : induction of ICAM-1 and VCAM-1 via
TNF receptor associated factor and protein kinase C-dependent
NF-kappaB activation in endothelial cells
Shishodia et al., Cancer Res 2005
(Carcinoma, Small Cell...) :
NF-kappaB dependent reporter gene expression was also suppressed by 4-HPR, as was
NF-kappaB reporter activity
induced by TNFR1, TRADD,
TRAF2 , NIK, and IKK but not that induced by p65 transfection ... NF-kappaB dependent reporter gene expression was also suppressed by 4-HPR, as was
NF-kappaB reporter activity
induced by TNFR1, TRADD,
TRAF2 , NIK, and IKK but not that induced by p65 transfection
Morlon et al., Hum Mol Genet 2005
(Ectodermal Dysplasia) :
TAB2,
TRAF6 and TAK1 are
involved in
NF-kappaB activation induced by the TNF-receptor, Edar and its adaptator Edaradd ... Moreover, we show that dominant negative forms of TAB2,
TRAF6 and TAK1
blocked the
NF-kappaB activation induced by Edaradd
Conti et al., J Neurosurg 2005
(Brain Neoplasms...) :
The authors investigated the expression of
NF-kappaB , caspase 3, TRAF1, TRAF2, and TRAF associated NF-kappaB activator/TRAF interacting protein ( TANK/I-TRAF ), a
regulator of
TRAF activity, in human gliomas
Guasparri et al., EMBO Rep 2006
:
TRAF2 and TRAF3 are
required for induction of
NF-kappaB and associated cell survival, as well as Jun amino-terminal kinase phosphorylation by vFLIP, whereas TRAF1, TRAF5 and TRAF6 are dispensable ...
TRAF2 , but not TRAF3,
mediates the association of vFLIP with the
IkappaB kinase complex
Maezawa et al., J Immunol 2006
(MAP Kinase Signaling System) :
We also found that IL-25R mediated
NF-kappaB activation was
inhibited by the expression of dominant negative TRAF6 but not of dominant negative
TRAF2
Sethi et al., J Biol Chem 2006
:
NF-kappaB reporter activity
induced by TNFR1, TNF receptor associated death domain,
TRAF2 , TAK1, NF-kappaB inducing kinase, and IKKbeta was inhibited by indirubin but not that induced by p65 transfection
Ryu et al., World J Gastroenterol 2006
(Hepatitis B) :
During the initial state of HBV infection, hepatocytes facilitate the
activation of
NF-kappaB through up regulation of LT-alpha,
TRAF2 , and NIK
Noels et al., J Biol Chem 2007
(Lymphoma, B-Cell, Marginal Zone...) :
In contrast,
TRAF6 was
essential for
NF-kappaB activation by all fusion variants, and we identified a novel TRAF6 binding site in the second immunoglobulin domain of MALT1, which enhanced NF-kappaB activation when present in the fusion protein ... Finally, binding of
TRAF2 to BIR1
contributed to
NF-kappaB activation by API2.MALT1, although additional mechanisms involving BIR1 mediated raft association are also important
Sung et al., Mol Pharmacol 2007
:
NF-kappaB dependent reporter gene expression was also suppressed by fisetin, as was
NF-kappaB reporter activity
induced by TNFR1, TRADD,
TRAF2 , NIK, and IKK but not that induced by p65 transfection ... NF-kappaB dependent reporter gene expression was also suppressed by fisetin, as was
NF-kappaB reporter activity
induced by TNFR1, TRADD,
TRAF2 , NIK, and IKK but not that induced by p65 transfection
Sethi et al., Oncogene 2007
(Adenocarcinoma...) :
Using dominant negative plasmids, we also demonstrated the
role of TRADD,
TRAF2 , NIK and Ras in EGF induced
NF-kappaB activation
Matta et al., J Biol Chem 2007
:
Furthermore, endogenously expressed
TRAF2 and TRAF3 do not interact with K13 and
play no role in K13 induced
NF-kappaB activation or its interaction with the IKK complex
Sethi et al., J Immunol 2007
:
NF-kappaB reporter assay revealed that
NF-kappaB activation
induced by TNF, TNFR1, TRADD,
TRAF2 , NIK, and I kappaB alpha kinase was modulated in gene deleted cells
Zarnegar et al., Proc Natl Acad Sci U S A 2008
:
Studies examining tumor-necrosis factor receptor associated factors ( TRAFs ) have identified positive
roles for TRAF2,
TRAF5 , and TRAF6, but not TRAF3, in canonical ( p50 dependent )
NF-kappaB activation
van Galen et al., Histopathology 2008
(Lymphoma, Large B-Cell, Diffuse) :
TRAF2 might be
involved in activation of
NF-kappaB in a subset of ABC-like DLBCL, and its expression is associated with a particularly poor outcome in primary nodal DLBCL patients
Sethi et al., Biochem Pharmacol 2008
(Neoplasm Invasiveness) :
This led to suppression of the phosphorylation and translocation of p65 and also of
NF-kappaB reporter activity
induced by TNFR1, TRADD,
TRAF2 , NIK, and IKKbeta but not that induced by p65 transfection
Blackwell et al., Mol Cell Biol 2009
(Lymphoma) :
Notably,
TRAF2 phosphorylation
increased both basal and inducible c-Jun and
NF-kappaB activities and rendered cells resistant to stress induced apoptosis
Garrison et al., Oncogene 2009
:
In addition, a dominant negative
TRAF2 mutant or downregulation of TRAF2 achieved by small interfering RNA
inhibited NF-kappaB activation by c-IAP2/MALT1 showing that TRAF2 is indispensable ... Comparisons of the bioactivity of intact c-IAP2/MALT1 oncoprotein and BIR1 E47A/R48A c-IAP2/MALT1 mutant that can not bind TRAF2 in a lymphoid cell line provided evidence that
TRAF2 interaction is
critical for c-IAP2/MALT1 mediated increases in the
NF-kappaB activity, increased expression of endogenous NF-kappaB target genes ( c-FLIP, TRAF1 ), and resistance to apoptosis
Dai et al., J Cell Mol Med 2010
:
We provide evidence that HSP70 over-expression can sequester
TRAF2 in detergent-soluble fractions possibly through interacting with TRAF2, leading to reduced recruitment of receptor interacting protein ( RIP1 ) and IkappaB alpha kinase (IKK) signalosome to the TNFR1-TRADD complex and
inhibited NFkappaB activation after TNFalpha stimuli ... Therefore, our study suggests that HSP70 may differentially regulate TNFalpha induced
activation of
NFkappaB and JNK through interaction with
TRAF2 , contributing to the pro-apoptotic roles of HSP70 in TNFalpha induced apoptosis of human colon cancer cells
Yamaguchi et al., Cell Biol Int 2009
(MAP Kinase Signaling System) :
JNK binding protein 1 regulates
NF-kappaB activation through
TRAF2 and TAK1
Graham et al., J Immunol 2009
:
Examination of
TRAF binding, degradation, cytokine production, IgM secretion, and the
activation of c-Jun kinase and
NF-kappaB revealed that some events are dictated by TRAF binding site sequences, others are partially regulated, and still others are independent of the TRAF binding site sequence
Park et al., Mol Cells 2009
:
Furthermore, LHDAg promoted
TRAF2 induced
NF-kappaB activation
Yamazaki et al., Science signaling 2009
:
After TAK1 mediated activation of NF-kappaB,
TRAF6 subsequently
activated NF-kappaB through MEKK3 independently of TAK1, thereby establishing continuous activation of NF-kappaB, which was required for the production of sufficient cytokines
Manna et al., J Biol Chem 2010
:
It
inhibits TRAF2 mediated
NF-kappaB activation but not TRAF6 mediated NF-kappaB DNA binding by preventing its association with TANK (
TRAF for NF-kappaB ) ... It inhibits
TRAF2 mediated
NF-kappaB activation but not TRAF6 mediated NF-kappaB DNA binding by preventing its association with TANK ( TRAF for NF-kappaB )
Song et al., Virus Genes 2010
:
Roles of
TRAF2 and TRAF3 in Epstein-Barr virus latent membrane protein 1-induced alternative
NF-kappaB activation
Rothe et al., Science 1995
:
Overexpression of
TRAF2 , but not TRAF1 or TRAF3, was
sufficient to induce
NF-kappa B activation
Song et al., Proc Natl Acad Sci U S A 1996
:
TRAF2 action is
required for activation of the transcription factor
NF-kappaB triggered by TNF and the CD40 ligand ... In cotransfection experiments, A20 blocked
TRAF2 mediated
NF-kappaB activation
Tewari et al., Curr Opin Genet Dev 1996
:
Significantly,
TRAF2 mediates the activation of
NF-kappa B by both receptors
Cao et al., Nature 1996
:
When overexpressed in human 293 cells,
TRAF6 activates
NF-kappaB
Duckett et al., Mol Cell Biol 1997
:
TRAF dependent induction of
NF-kappaB appears to be regulated by the relative levels of individual TRAF proteins in the cell
Tsitsikov et al., Proc Natl Acad Sci U S A 1997
:
These results suggest that CD30 ligation may enhance the expression of HIV via
TRAF-2 mediated activation of
NF-kappaB
Lee et al., J Exp Med 1997
:
TRAF interacting protein (TRIP) : a novel component of the tumor necrosis factor receptor (TNFR)- and CD30-TRAF signaling complexes that inhibits
TRAF2 mediated
NF-kappaB activation ... When associated, TRIP inhibits the
TRAF2 mediated
NF-kappaB activation that is required for cell activation and also for protection against apoptosis
Min et al., J Immunol 1997
:
Transient overexpression of the
TRAF2 adaptor protein can
activate NF-kappaB and endogenous JNK, whereas N-terminal truncated TRAF2 protein blocks TNF induced NF-kappa B and JNK activation as well as E-selectin promoter-reporter gene transcription
Lee et al., Immunity 1997
(Hypertrophy...) :
TRAF2 is
essential for JNK but not
NF-kappaB activation and regulates lymphocyte proliferation and survival
Relaix et al., Nat Genet 1998
:
TNF signal transduction is mediated by
TRAF2 which binds the TNF Receptor2 (TNFR2) and
activates NFkappaB ... Transfection of a truncated Peg3 containing the TRAF2 interaction site, abolishes
NFkappaB activation by
TRAF2 and/or TNF
Miller et al., Mol Cell Biol 1998
:
Overexpression of
TRAF2 potently
activates NF-kappaB , although TRAF2 did not induce expression of the EGFR either alone or in combination with TRAF1 and TRAF3
Akiba et al., J Biol Chem 1998
:
These results indicate that
TRAF2 and TRAF5 are
involved in
NF-kappaB and SAPK/JNK activation by CD27, and NIK is a common downstream kinase of TRAF2 and TRAF5 for NF-kappaB and SAPK/JNK activation
Thome et al., Curr Biol 1998
:
CARDIAK interacted with the TNFR associated factors TRAF-1 and TRAF-2, and a dominant negative form of
TRAF-2 inhibited CARDIAK induced
NF-kappa B activation
Geleziunas et al., Mol Cell Biol 1998
(Cell Transformation, Viral...) :
However, plasma membrane-proximal elements in these proinflammatory cytokine pathways are apparently not involved since dominant negative mutants of the
TRAF2 and TRAF6 adaptors, which effectively block signaling through the cytoplasmic tails of the TNF-alpha and IL-1 receptors, respectively, do not
inhibit Tax induction of
NF-kappaB
Wong et al., J Biol Chem 1998
:
Dominant negative forms of TRAF2,
TRAF5 , and TRAF6 and an endogenous inhibitor of TRAF2, TRAF interacting protein (TRIP), substantially
inhibited TRANCE-R mediated
NF-kappaB activation, suggesting a role of TRAFs in regulating DC and osteoclast function ... Dominant negative forms of TRAF2, TRAF5, and TRAF6 and an endogenous inhibitor of
TRAF2 , TRAF interacting protein (TRIP), substantially
inhibited TRANCE-R mediated
NF-kappaB activation, suggesting a role of TRAFs in regulating DC and osteoclast function
Tsukamoto et al., Proc Natl Acad Sci U S A 1999
:
Furthermore, NFkappaB activation by cyt-C is inhibited by a kinase negative form of NFkappaB inducing kinase more efficiently than that by cyt-N, consistent with the result that
NFkappaB activation by
TRAF2 and TRAF5 is inhibited by a kinase negative form of NFkappaB inducing kinase more efficiently than that by TRAF6