◀ Back to RELA
RELA — TRAF3
Pathways - manually collected, often from reviews:
-
KEGG Pathways in cancer:
NFKB1/NFKB2/RELA
→
TRAF1/TRAF2/TRAF3/TRAF4/TRAF5/TRAF6
(gene expression, expression)
-
KEGG Small cell lung cancer:
NFKB1/RELA
→
TRAF1/TRAF2/TRAF3/TRAF4/TRAF5/TRAF6
(gene expression, expression)
Text-mined interactions from Literome
Leo et al., J Biol Chem 1999
:
A carboxyl-truncation mutant of CD40 lacking the last 32 amino acids required for TRAF2 and
TRAF3 binding, CD40 ( Delta32 ), mediated
NF-kappaB induction through a mechanism that was suppressible by co-expression of TRAF6 ( DeltaN ), a dominant negative version of TRAF6, but not by TRAF2 ( DeltaN ), implying that while TRAF6 does not directly bind CD40, it can participate in CD40 signaling
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
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
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
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 ... 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 ... C-terminal deletion mutants as well as the N-terminal deletion mutant of
TRAF3 inhibited
NF-kappaB activation induced by OX40 or TRAF2 ... Thus, it is suggested that
TRAF3 actively
inhibits NF-kappaB activation induced by OX40
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
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
Xu et al., J Immunol 2002
:
Moreover, overexpression of
TRAF3 inhibits BAFF-R mediated
NF-kappaB activation and IL-10 production
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
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
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
Dadgostar et al., FEBS Lett 2003
:
More importantly, T3JAM and
TRAF3 synergistically
activate JNK but not
nuclear factor (NF)-kappaB
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
Hauer et al., Proc Natl Acad Sci U S A 2005
:
We observed that
TRAF3 specifically
blocked the
NF-kappaB activation via TRAF2/5
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
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
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
He et al., J Exp Med 2006
:
25 : 280-288 ). We demonstrate that loss of tumor necrosis factor
(TNF) receptor associated factor 3 ( TRAF3 )
results in constitutive noncanonical
NF-kappaB activity
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
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
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 ... 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 ... In this article, we provide evidence that
TRAF3 potently
suppresses canonical
NF-kappaB activation and gene expression in vitro and in vivo
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
Alff et al., J Virol 2008
:
In contrast, the Gn tail of the nonpathogenic hantavirus Prospect Hill virus ( PHV ) failed to coprecipitate
TRAF3 or
inhibit NF-kappaB or IFN-beta transcriptional responses
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
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
Yao et al., J Clin Invest 2009
(Bone Resorption) :
These findings suggest that upregulation of
TRAF3 or NF-kappaB p100 expression or
inhibition of
NF-kappaB p100 degradation in OCPs could limit bone destruction and inflammation induced bone loss in common bone diseases
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 )
Ikeda et al., FEBS Lett 2010
:
Regarding the mechanisms involved, we found that BS69 directly interacted with
TRAF3 , a negative
regulator of
NF-kappaB activation ... Furthermore, small interfering RNA mediated knockdown experiments revealed that
TRAF3 was
involved in the BS69 mediated suppression of LMP1/CTAR1 induced
NF-kappaB activation
Bista et al., J Biol Chem 2010
:
TRAF3 controls activation of the canonical and alternative
NFkappaB by the lymphotoxin beta receptor ... Increased expression of
TRAF3 correlated with its increased recruitment to LTBR induced signaling complexes, decreased recruitment of TRAF2, and
attenuated phosphorylation of IkappaB alpha and
RelA
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
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
:
NF-kappaB induction through domain 2 was
inhibited by coexpression of either full-length
TRAF3 or dominant negative forms of TRAF1 or TRAF2 ...
TRAF dependent induction of
NF-kappaB appears to be regulated by the relative levels of individual TRAF proteins in the cell
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
Yamamoto et al., J Immunol 1998
:
This
NF-kappaB activation signal is
inhibited by dominant negative TRAF2 or intact
TRAF3 , indicating that TRAF2 and TRAF3 works as a mediator and an inhibitor, respectively