ライフサイエンスコーパス: TRAF3

1 ination of TNF receptor-associated factor 3 (TRAF3).

2 d ubiquitination of TNFR-associated factor3 (TRAF3).

3 signaling protein TNFR-associated factor 3 (TRAF3).

4 le to bind TNF receptor-associated factor 3 (TRAF3).

5 atening disease, as illustrated by STAT1 and TRAF3.

6 abilization by MACs did not involve cIAP2 or TRAF3.

7 diated deubiquitination and stabilization of TRAF3.

8 ated NIK, p100 processing to p52 and reduced TRAF3.

9 ted LTbetaR competitively displaced NIK from TRAF3.

10 aling, whereas CD40 signals are inhibited by TRAF3.

11 for TRIF-related adaptor molecule (TRAM) and TRAF3.

12 ctive degradation of the signalling scaffold TRAF3.

13 eding times were not affected by deletion of TRAF3.

14 receptor (TNFR)-associated factors TRAF2 and TRAF3.

15 w molecular determinant of USP7 recognition, TRAF3/6-specific targeting by the deubiquitinase, associ

16 adation of TNF receptor-associated factor 3 (Traf3), a potent inhibitor of mitogen-activated protein

17 s factor (TNF) receptor-associated factor 3 (TRAF3), a TBK1 complex component required for IRF3 activ

18 Unexpectedly, one top hit was Traf3, a negative regulator of NF-kappaB signaling that

19 hat both NS1 and NS2 decreased the levels of TRAF3, a strategic integrator of multiple IFN-inducing s

20 mutation in the receptor-binding crevice of TRAF3 ablated binding of both LTbetaR and NIK suggesting

21 We found that TRAF3 ablation did not affect the maturation or homeosta

22 TRAF3 also associated with and regulated the TCR/CD28 in

23 TRAF3 also plays a unique cell type-specific and critica

24 s that TRAF proteins, particularly TRAF2 and TRAF3, also regulate signal transduction by controlling

25 olvement and provide a mechanistic basis for Traf3 alternative splicing and ncNFkappaB activation in

26 tely 9% of DLBCLs, and reduced expression of TRAF3 among deleted cases.

27 ression of TNF receptor-associated factor 3 (TRAF3), an adapter protein that regulates NF-kappaB p100

28 in TEC of TNF receptor-associated factor 3 (TRAF3), an inhibitor of nonclassical NF-kappaB signaling

29 In the absence of TRAF3, anaerobic glycolysis and oxidative phosphorylatio

30 aB pathway was regulated upon degradation of TRAF3 and activation of NIK.

31 phorylation of Stat6 and in sequestration of Traf3 and DISC1 to the cytoskeleton.

32 anscription, was increased in the absence of TRAF3 and enhanced Mcl-1 was suppressed with CREB inhibi

33 1 was previously shown to decrease levels of TRAF3 and IKKepsilon, whereas NS2 interacted with RIG-I

34 in cultured cells confirmed the link between TRAF3 and NF-kappaB2/inflammation.

35 We conclude that RAB1B regulates TRAF3 and promotes the formation of innate immune signal

36 reas NS2 interacted with RIG-I and decreased TRAF3 and STAT2.

37 reveal important interplay between GAPDH and TRAF3 and suggest a mechanism by which the NleB effector

38 also shown to bind TRAF3, and the binding of TRAF3 and TBK1 to DOK3 required the tyrosine-rich C-term

39 thways required the presence of RIG-I, IPS1, TRAF3 and TBK1, only the apoptotic pathway required the

40 the interaction of TRAF3IP3 with endogenous TRAF3 and TBK1.

41 interactions between the E3 ubiquitin ligase TRAF3 and TBK1/IKKi to attenuate lysine 63-linked polyub

42 asome-dependent mechanism that also requires TRAF3 and the E3 ubiquitin ligase cIAP.

43 ell cycle arrest, whereas siRNA knockdown of TRAF3 and the NF-kappaB inhibitor IkappaB prevented the

44 Ligated LTbetaR complexed with TRAF3 and TRAF2 redirected the specificity of the ubiqui

45 Furthermore, the recruitment of TRAF3 and TRAF2 to the ligated LTbetaR competitively dis

46 biquitin ligase reaction to polyubiquitinate TRAF3 and TRAF2, leading to their proteosomal degradatio

47 s restrained by B cell-intrinsic checkpoints TRAF3 and TRAF2, whose deletion in B cells enables the B

48 ontained decreased amounts of both TRAF2 and TRAF3 and TRAF2-associated signaling proteins.

49 s study, we show that hCD40-P227A binds more TRAF3 and TRAF5, as well as certain associated proteins,

50 ctions with innate immune signaling proteins TRAF3 and TRAF6, and that vIRF-2 targeting of USP7 regul

51 ma also bind to the TLR adaptors and to both TRAF3 and TRAF6.

52 n (MAVS) and inhibiting its association with TRAF3 and TRAF6.

53 a target of NleB during infection, bound to TRAF3 and was required for maximal TRAF3 ubiquitination.

54 ls purified from young adult B cell-specific Traf3 (-/-) and littermate control mice.

55 ecrosis factor receptor-associated factor 3 (TRAF3) and for production of the antiinflammatory cytoki

56 iated with TNF receptor-associated factor 3 (TRAF3) and promotes TRAF3 lysine 63-linked ubiquitinatio

57 including TNF receptor-associated factor 3 (TRAF3) and TANK-binding kinase 1 (TBK1), to form a signa

58 upon the relationship between ubiquitin and TRAF3, and how this contributes to multiple functions of

59 NLRP12 interacted with both NIK and TRAF3, and Nlrp12(-/-) cells have constitutively elevate

60 way is differentially regulated by TRAF2 and TRAF3, and that distinct interactions of LMP1 and its ef

61 DOK3 was also shown to bind TRAF3, and the binding of TRAF3 and TBK1 to DOK3 require

62 ase AIP4 to trigger the degradation of MAVS, TRAF3, and TRAF 6.

63 This correlates with increased TRAF2, TRAF3, and TRAF6 recruitment to His159Tyr BAFF-R.

64 tin moieties from proteins, including TRAF2, TRAF3, and TRAF6.

65 The assembly of MyD88 death domain (DD) with TRAF3 (anti-viral/anti-inflammatory) and TRAF6 (pro-infl

66 mphoma (DLBCL) tumors and identified loss of TRAF3 as a common event, affecting approximately 9% of D

67 Our data illustrate the function of TRAF3 as a dual-mode repressor of LTBR signaling that co

68 These findings establish TRAF3 as a mediator of Treg cell function in the regulat

69 the potential utility of cBCLs with mutated TRAF3 as a model of the more aggressive activated B-cell

70 doesn't induce TRAF degradation, and employs TRAF3 as a positive mediator of cell signaling, whereas

71 B cell lines revealed that hCD40-P227A uses TRAF3 as a positive rather than negative regulator.

72 at improves our understanding of the role of TRAF3 as a tumor suppressor, and suggests potential ther

73 Our results identify a role for TRAF3 as an important negative regulator of signaling vi

74 genes further implicated TNFAIP3, KMT2D, and TRAF3 as recurrent targets of somatic mutation based on

75 identified TNF receptor-associated factor 3 (TRAF3) as a regulator of Treg cell function.

76 isoform of TNF receptor-associated factor 3 (Traf3) as formation of a NIK-Traf3-Traf2 complex targets

77 TRAF3 associated with Csk, promoting the dissociation of

78 to trigger K33-linked polyubiquitination of TRAF3 at Lys168, which was then detected by RalGDS, a gu

79 TRAF3 autophagy is driven by RAS and results in activati

80 tantially reversed the survival phenotype of Traf3 (-/-) B cells both in vitro and in vivo.

81 ne synthesis and was strikingly increased in Traf3 (-/-) B cells, substantially reversed the survival

82 synthesis supports the prolonged survival of Traf3 (-/-) B lymphocytes.

83 CREB protein was elevated in TRAF3(-/-) B cells, without change in mRNA, but with a d

84 signaling, and CD40 signals are amplified in TRAF3(-/-) B cells.

85 urther analysis of GnT domains revealed that TRAF3 binding is a discrete GnT function, independent of

86 e cytoplasmic tail of BAFF-R adjacent to the TRAF3 binding motif.

87 glycosyltransferase activity inhibited GAPDH-TRAF3 binding, resulting in reduced TRAF3 ubiquitination

88 that add degrons to TULV or PHV GnTs confer TRAF3 binding.

89 AF3 bridge where TRAF2 recruits c-IAP1/2 and TRAF3 binds to NIK.

90 lose proximity to the c-IAPs through a TRAF2-TRAF3 bridge where TRAF2 recruits c-IAP1/2 and TRAF3 bin

91 taR signaling component that associates with TRAF3 but not with TNFR-associated factor 2 (TRAF2).

92 y protein, TNF receptor-associated factor 3 (TRAF3), but how this signalling event is controlled is s

93 The ubiquitination of TRAF3 by NEDD4 is critical for CD40-mediated AKT activat

94 component TNF receptor-associated factor 3 (TRAF3) by the VDRA paricalcitol was studied in PBMCs fro

95 In contrast, TRAF3 can serve as a negative regulator of CD40 signalin

96 aB-inducing kinase (NIK) levels (NIK, TRAF2, TRAF3, cIAP1&2, and CD40) activate the alternative but o

97 The EWS:TRAF3 complex forms under unligated conditions that are

98 In B lymphocytes, TRAF3 contributes to regulation of signaling by members

99 Increased expression of TRAF3 correlated with its increased recruitment to LTBR-

100 TRAF3 dampened interleukin 2 (IL-2) signaling by facilit

101 TRAF3 deficiency also disrupts autoreactive B cell anerg

102 TRAF3 deficiency also led to a Pim2-dependent increase i

103 Uniquely in B cells, TRAF3 deficiency enhances survival and increases the ris

104 We show that TRAF3 deficiency led to induction of two proteins import

105 TRAF3 deficiency permits BCR-induced CSR by elevating BC

106 B cell-specific TRAF3 deficiency results in enhanced viability and is as

107 These results indicate that TRAF3 deficiency suffices to metabolically reprogram B c

108 We found that TRAF3 deficiency was associated with induction of the pr

109 We showed that TRAF3 deficiency-associated autoimmune phenotypes can be

110 mal treatments for human B-cell cancers with TRAF3 deficiency.

111 distal signaling events were compromised by TRAF3 deficiency.

112 nd characterization of myeloid cell-specific TRAF3-deficient (M-TRAF3(-/-)) mice, which allowed us to

113 Combination treatment of TRAF3-deficient B cells and B cell tumor lines with c-My

114 F-kappaB2 is required for BCR-induced CSR in TRAF3-deficient B cells but not for CD40-induced or LPS-

115 TRAF3-deficient B cells were also preferentially sensiti

116 antially attenuated the enhanced survival of TRAF3-deficient B cells, with a decrease in the pro-surv

117 ed transcriptional activity was increased in TRAF3-deficient B cells.

118 TRAF3-deficient iNKT cells in CD4(Cre)TRAF3(flox/flox) (

119 eloid cells in young adult mice, even though TRAF3-deficient macrophages and neutrophils exhibited co

120 to mice lacking TRAF3 in B cells, the T cell TRAF3-deficient mice exhibited defective IgG1 responses

121 promotes proximal TCR signaling, we studied TRAF3-deficient mouse and human T cells, which showed a

122 TRAF3-deficient primary B cells were less sensitive to c

123 lation through 4-1BB induces cIAP1-dependent TRAF3 degradation and activation of the alternative NF-k

124 ly, NIK stabilization was not accompanied by TRAF3 degradation demonstrating that RP3 disrupts normal

125 RANKL induced TRAF3 degradation via the lysosome/autophagy system.

126 mbers, NIK becomes stabilized as a result of TRAF3 degradation, leading to the activation of noncanon

127 -mediated TNFR-associated factor (TRAF)2 and TRAF3 degradation.

128 was associated with decreased RANKL-induced TRAF3 degradation.

129 Mice with TRAF3 deleted in MPCs develop early onset osteoporosis d

130 TRAF3 deletion in MPCs activated NF-kappaB RelA and RelB

131 We further observed that TRAF3 deletion is also capable of overcoming all require

132 erapeutic value for B cell malignancies with TRAF3 deletions or relevant mutations.

133 s factor (TNF) receptor-associated factor-3 (TRAF3)-dependent E3 ubiquitin ligase.

134 moniae expresses a unique protease targeting TRAF3-dependent immune effector mechanisms.

135 These effects of TRAF3 depletion did not require LTBR signaling and were

136 Although the loss of TRAF3 did not reduce the overall frequency of Treg cells

137 ic tails (GnTs) that inhibit RIG-I/MAVS/TBK1-TRAF3-directed IFN-beta induction.

138 cells of B-cell-specific TRAF3(-/-) mice (B-Traf3(-/-)) display remarkably enhanced survival compare

139 ce with renal injury, paricalcitol prevented TRAF3 downregulation and NF-kappaB2-dependent gene upreg

140 conclude that pharmacologic stabilization of TRAF3 during aging could treat/prevent age-related osteo

141 Recent evidence suggests that the cIAP-TRAF2-TRAF3 E3 complex also targets additional signaling facto

142 TRAF2 in regulating NIK degradation, whereas TRAF3 enhances but is not essential for cIAP1/2-mediated

143 Taken together, our findings indicate that TRAF3 expressed in myeloid cells regulates immune respon

144 uced OC formation and function by increasing TRAF3 expression in OCPs in vitro and in vivo.

145 ption factor gene Relb resulted in increased TRAF3 expression in OCPs, which was associated with decr

146 KRAS, NRAS, MAX, HIST1H1E, RB1, EGR1, TP53, TRAF3, FAM46C, DIS3, BRAF, LTB, CYLD, and FGFR3.

147 TRAF3-deficient iNKT cells in CD4(Cre)TRAF3(flox/flox) (T-TRAF3(-/-)) mice exhibit defective u

148 TRAF2 and TRAF3 form a complex with the E3 ubiquitin ligase cIAP (

149 Specific deletion of the tumor suppressor TRAF3 from B lymphocytes in mice leads to the prolonged

150 Here, we report that TRAF3 functions as a negative regulator of LTBR signalin

151 cell-specific TRAF3(-/-) mice, in which the traf3 gene was deleted from thymocytes and T cells.

152 tor, and TNF receptor-associated receptor 3 (TRAF3); however, a role for TRAF3 in RANKL-mediated OC f

153 th tubulin, actin, TNFR-associated factor-3 (Traf3), IL-13R1, and DISC1.

154 Treg cell-specific ablation of TRAF3 impaired CD4 T cell homeostasis, characterized by

155 equired the RING domain of TRAF2, but not of TRAF3, implicating TRAF2 as a key E3 ligase in TRAF turn

156 rovided by SP T cells are needed to overcome TRAF3-imposed arrest in mTEC development mediated by inh

157 etabolites, lipids, and enzymes regulated by TRAF3 in B cells are clustered in the choline metabolic

158 In striking contrast to mice lacking TRAF3 in B cells, the T cell TRAF3-deficient mice exhibi

159 , information highly relevant to the role of TRAF3 in B-cell malignancies.

160 and dramatically changes the role played by TRAF3 in CD40 signaling.

161 of antibody responses and suggest a role for TRAF3 in mediating ICOS expression in Treg cells.

162 However, the role of TRAF3 in mesenchymal progenitor cells (MPCs) is unknown.

163 TGFbeta1 induces degradation of TRAF3 in murine MPCs and inhibits osteoblast formation t

164 IFN production, but the in vivo function of TRAF3 in myeloid cells remains unknown.

165 gain insights into the in vivo functions of TRAF3 in myeloid cells.

166 hese findings identify a new role for T cell TRAF3 in promoting T cell activation, by regulating loca

167 ated receptor 3 (TRAF3); however, a role for TRAF3 in RANKL-mediated OC formation is unknown.

168 gs provide insights into the roles played by TRAF3 in T cell activation and T cell-mediated immunity.

169 However, the specific function of TRAF3 in T cells has remained unclear.

170 ow this contributes to multiple functions of TRAF3 in the regulation of signal transduction, transcri

171 Here, we report a new mechanism for TRAF3 in the restraint of B cell survival.

172 Ablation of TRAF3 in the T cell lineage did not affect CD4 or CD8 T

173 A well-recognized function of TRAF2 and TRAF3 in this aspect is to mediate ubiquitin-dependent d

174 Deletion of TRAF3 in thymic epithelial cells allowed RelB-dependent

175 Moreover, the ablation of TRAF3 in Treg cells resulted in increased antigen-stimul

176 ermore, we confirmed the association between TRAF3 inactivation and increased transcriptional activit

177 In addition, mature TRAF3(-/-) iNKT cells displayed defective cytokine respo

178 sition results from reduced TCR signaling in TRAF3(-/-) iNKT cells.

179 TRAF3 interacting protein 2 (TRAF3IP2) is important for

180 TRAF3IP2 (TRAF3 interacting protein 2; previously known as CIKS or

181 TRAF3IP2 (TRAF3 Interacting Protein 2; previously known as CIKS or

182 e have identified a Golgi-associated factor, TRAF3-interacting protein 3 (TRAF3IP3), as a crucial med

183 TRAF3-interacting protein 3 (TRAF3IP3, T3JAM) is essenti

184 biquitination in K48-linked chains and cIAP1-TRAF3 interaction mediated the mechanisms of paricalcito

185 ere for the first time to our knowledge that TRAF3 is a resident nuclear protein that associates with

186 TRAF3 is a signaling molecule crucial for type I IFN pro

187 TRAF3 is a versatile intracellular adapter protein with

188 ting the relative strength of TCR signaling, TRAF3 is an important regulator of iNKT cell development

189 ate that autophagic/lysosomal degradation of TRAF3 is an important step in RANKL-induced NF-kappaB ac

190 TRAF3 is central in the activation of the NADPH oxidase

191 We determined that GnT binding to TRAF3 is mediated by C-terminal degrons within NY-1V or

192 eases the risk of transformation, as loss of TRAF3 is observed in several types of B cell cancers.

193 In vitro studies showed that TRAF3 is required for TLR-induced type I IFN production,

194 or protein TNF receptor-associated factor 3 (TRAF3) is a critical regulator of B lymphocyte survival.

195 factor receptor (TNFR)-associated factor 3 (TRAF3) is both modified by and contributes to several ty

196 n-dependent alternative splicing generates a Traf3 isoform lacking exon 8 (Traf3DE8) that, in contras

197 TRAF3 knock-down also increased mRNA and protein express

198 ng that increased platelet activation in the TRAF3 knockout mice was not due to increased expression

199 t aggregation and secretion are increased in TRAF3 knockout mice.

200 sis model was significantly shortened in the TRAF3 knockout mice.

201 Conditional OC-specific Traf3-KO (cKO) mice had mild osteoporosis and increased

202 Circulating TRAF3 levels could be a biomarker of renal damage associ

203 Furthermore, treatments that increase TRAF3 levels in OCPs, including pharmacological inhibiti

204 Modulation of cellular TRAF3 levels may thus contribute to regulation of NFkapp

205 revealed an inverse association of cellular TRAF3 levels with LTBR-specific defect in canonical NFka

206 ivation of NFkappaB by TNF did not depend on TRAF3 levels.

207 TRAF3 limits bone destruction by inhibiting RANKL-induce

208 We found that TRAF3 limits RANKL-induced osteoclastogenesis by suppres

209 To determine whether TRAF3 loss might be relevant to human NHL, we also analy

210 tor-associated factor 3 (TRAF3) and promotes TRAF3 lysine 63-linked ubiquitination.

211 cocker spaniels, with recurrent mutations in TRAF3-MAP3K14 (28% of all cases), FBXW7 (25%), and POT1

212 tudy, we investigated the metabolic basis of TRAF3-mediated regulation of B cell survival by employin

213 hus, our studies highlight the importance of TRAF3-mediated restraint on BCR signaling strength for c

214 In TRAF3(-/-) MEFs, CTAR1 induced nuclear p50 but did not a

215 B cells of B-cell-specific TRAF3(-/-) mice (B-Traf3(-/-)) display remarkably enhanc

216 osinic-polycytidylic acid (a viral mimic), M-TRAF3(-/-) mice exhibited an altered profile of cytokine

217 thymocytes, except that the T cell-specific TRAF3(-/-) mice had a 2-fold increase in FoxP3(+) T cell

218 M-TRAF3(-/-) mice immunized with T cell-independent and -d

219 Consistently, development of iNKT cells in T-TRAF3(-/-) mice shows a major defect at developmental st

220 Interestingly, 15- to 22-mo-old M-TRAF3(-/-) mice spontaneously developed chronic inflamma

221 tion and characterization of T cell-specific TRAF3(-/-) mice, in which the traf3 gene was deleted fro

222 nt iNKT cells in CD4(Cre)TRAF3(flox/flox) (T-TRAF3(-/-)) mice exhibit defective up-regulation of T-be

223 of myeloid cell-specific TRAF3-deficient (M-TRAF3(-/-)) mice, which allowed us to gain insights into

224 flammatory actions of paricalcitol depend on TRAF3 modulation and subsequent inhibition of the noncan

225 holine biosynthesis was markedly elevated in Traf3 (-/-) mouse B cells and decreased in TRAF3-reconst

226 ll, 30% of the tumors contained >/=1 somatic TRAF3 mutation.

227 with these findings, loss-of-function human TRAF3 mutations are common in B-cell cancers, particular

228 ding the TRAF1/TRAF2 positive regulators and TRAF3 negative regulator of NF-kappaB transcription fact

229 rs of the NF-kappaB pathway, including CYLD, TRAF3, NFKBIA and NLRC5, in a total of 41% of cases.

230 ciated signaling complexes, including TRAF2, TRAF3, NIK, IKK1, and IKK2 have been shown to participat

231 ted in unstimulated cells by a cIAP1/2:TRAF2:TRAF3:NIK complex.

232 The impact of TRAF3 on this very early signaling event led to the hypo

233 These findings suggest that upregulation of TRAF3 or NF-kappaB p100 expression or inhibition of NF-k

234 diated the mechanisms of paricalcitol action.TRAF3 overexpression by CRISPR/Cas9 technology mimicked

235 We conclude that TRAF3 plays a central role in regulation of mTEC develop

236 Thus, TRAF3 plays a negative role in platelet activation and i

237 TRAF3 plays a variety of context-dependent regulatory ro

238 show that TNF receptor associated factor 3 (TRAF3) plays a critical role in the transition between t

239 Thus, TRAF3 positively regulates MPC differentiation into oste

240 Inhibition of degradative ubiquitination of TRAF3 prevented the expression of all proinflammatory cy

241 In young mice TRAF3 prevents beta-catenin degradation in MPCs and main

242 siRNA-mediated depletion of TRAF3 promoted recruitment of TRAF2 and IKK1 to activate

243 To determine how TRAF3 promotes proximal TCR signaling, we studied TRAF3-

244 of mutations are predicted to cause loss of TRAF3 protein including those impacting reading frame an

245 However, TRAF3 protein levels decrease in murine and human bone s

246 In PBMCs isolated from patients with ESKD, TRAF3 protein levels were lower than in healthy controls

247 nd deubiquitinates TRAF3, thereby inhibiting TRAF3 proteolysis and preventing aberrant non-canonical

248 in PIK3CA, KMT2D, FGFR3, FBXW7, DDX3X, PTEN, TRAF3, RB1, CYLD, RIPK4, ZNF750, EP300, CASZ1, TAF5, RBL

249 n Traf3 (-/-) mouse B cells and decreased in TRAF3-reconstituted human multiple myeloma cells.

250 Our findings suggest that TRAF3-regulated choline metabolism has diagnostic and th

251 ts identify a new mechanism by which nuclear TRAF3 regulates B-cell survival via inhibition of CREB s

252 or protein TNF receptor-associated factor 3 (TRAF3) regulates signaling through B-lymphocyte receptor

253 Stimulus-dependent degradation of TRAF3 required the RING domain of TRAF2, but not of TRAF

254 Ablation of Traf3 restores microglial activation and CNS inflammatio

255 y signaling event led to the hypothesis that TRAF3 restrains one or both of two known inhibitors of L

256 -induced or LPS-induced CSR, suggesting that TRAF3 restricts NF-kappaB2 activation to specifically li

257 T cell-specific deficiency in TRAF3 resulted in a two- to threefold greater frequency

258 Loss of TRAF3 resulted in increased amounts of both Csk and PTPN

259 Although this distinct modification of TRAF3 served to connect innate immune signaling to the c

260 uitin ligase cIAP (cIAP1 or cIAP2), in which TRAF3 serves as the NIK-binding adapter.

261 TRAF3 signaling in Treg cells was required to maintain h

262 TRAF3 siRNA prevented TNF-induced NF-kappaB p100 accumul

263 We demonstrate that loss of Traf3 specifically activates noncanonical NF-kappaB sign

264 CD40L-mediated death as involving sequential TRAF3 stabilisation, ASK1 phosphorylation, MKK4 (but not

265 n platelets were not affected by deletion of TRAF3, suggesting that increased platelet activation in

266 nteractions and residues required to inhibit TRAF3-TBK1-directed IFN-beta induction and IRF3 phosphor

267 restrict antiviral signaling by disrupting a TRAF3-TBK1-IKKi signaling complex.

268 positive role in TLR3 signaling by enabling TRAF3/TBK1 complex formation and facilitating TBK1 and I

269 aB stimuli, OTUD7B binds and deubiquitinates TRAF3, thereby inhibiting TRAF3 proteolysis and preventi

270 TRAF3 thus suppresses a Pim2-mediated B cell survival ax

271 -63 polyubiquitylation of its target protein TRAF3 (TNF receptor-associated factor 3).

272 finding that it forms a protein complex with TRAF3 to facilitate the interaction of TRAF3 with mitoch

273 ditionally, we found the E3 ubiquitin ligase TRAF3 to play a critical role in promoting TBK1-IKKi ubi

274 AF3 was necessary and sufficient to localize TRAF3 to the nucleus via a functional nuclear localizati

275 eceptor-associated factor 2 (TRAF2), but not TRAF3, to HVEM that specifically activated the RelA but

276 Traf3DE8 disrupts the NIK-Traf3-Traf2 complex and allows accumulation of NIK to in

277 iated factor 3 (Traf3) as formation of a NIK-Traf3-Traf2 complex targets NIK for degradation.

278 y) and TRAF6 (pro-inflammatory) suggest that TRAF3/TRAF6 binding sites on MyD88 DD partially overlap,

279 to and activation of the downstream effector TRAF3 (tumor necrosis factor receptor-associated factor

280 Decreased TRAF3 ubiquitination in K48-linked chains and cIAP1-TRAF

281 associated PTPN22W variant failed to promote TRAF3 ubiquitination, type 1 IFN upregulation, and type

282 ed GAPDH-TRAF3 binding, resulting in reduced TRAF3 ubiquitination.

283 bound to TRAF3 and was required for maximal TRAF3 ubiquitination.

284 We observed that GnTs bind TRAF3 via residues within the TRAF-N domain (residues 39

285 Here we found that the adaptor TRAF3 was intrinsically required for restraining the lin

286 The TRAF-C domain of TRAF3 was necessary and sufficient to localize TRAF3 to

287 In contrast, degradative ubiquitination of TRAF3 was not affected in the absence of IL-1R1 signalin

288 Surprisingly, we found that TRAF3 was recruited to the TCR/CD28 signaling complex up

289 ely cleaves K63-linked ubiquitin chains from TRAF3, was up-regulated in the absence of IL-1R1 signali

290 e uptake and B cell number in the absence of TRAF3 were all dependent upon NF-kappaB inducing kinase

291 alignant B cell lines with low expression of TRAF3 were more sensitive to Pim inhibition-induced cell

292 with interferon and targets STING, MAVS and TRAF3, which are critical factors for interferon express

293 We found mutations affecting TRAF3, which encodes a negative regulator of nuclear fac

294 the association of TBK1 with ICOS, TRAF2 and TRAF3, which identified a TBK1-binding consensus.

295 Noncanonical K63-linked ubiquitination of TRAF3, which is essential for type I IFN and IL-10 produ

296 ed by C. pneumoniae-dependent degradation of TRAF3, which is independent of a functional proteasome.

297 Here we show that platelet also express TRAF3, which plays a negative role in regulating platele

298 with TRAF3 to facilitate the interaction of TRAF3 with mitochondrial antiviral signaling protein.

299 D, and DUBA prevent association of TRAF6 and TRAF3 with their partners, in addition to removing K63-l

300 Also, TRAF3, X-linked inhibitor of apoptosis, and Bcl-X(L) exp