ライフサイエンスコーパス: TRAF3

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

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

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

4 eding times were not affected by deletion of TRAF3.

5 diated deubiquitination and stabilization of TRAF3.

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

7 ted LTbetaR competitively displaced NIK from TRAF3.

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

9 aling, whereas CD40 signals are inhibited by TRAF3.

10 cytosol upon c-IAP1/2-induced degradation of TRAF3.

11 on required TRAF6 and RIP1, but not TRAF2 or TRAF3.

12 ttle is known about the in vivo functions of TRAF3.

13 ctive degradation of the signalling scaffold TRAF3.

14 atening disease, as illustrated by STAT1 and TRAF3.

15 abilization by MACs did not involve cIAP2 or TRAF3.

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

19 Here we show that TRAF3, a ubiquitin ligase that interacts with both MyD88

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 ecrosis factor receptor-associated factor 3 (TRAF3), an adaptor protein essential for the IFN-I respo

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

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

31 irect interaction between the TRAF domain of TRAF3 and a TRAF-interaction motif (TIM) within Cardif.

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

33 ome-mediated degradation regulated by TRAF2, TRAF3 and cIAP1 or cIAP2.

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

35 ining adaptor inducing interferon-beta), and TRAF3 and downstream mediators TANK-binding kinase 1, in

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

37 Loss of the TRAF3 and IKKepsilon proteins appeared to involve a nonp

38 1 was previously shown to decrease levels of TRAF3 and IKKepsilon, whereas NS2 interacted with RIG-I

39 Y-1V Gn tail blocked TBK1 coprecipitation of TRAF3 and infection by NY-1V, but not PHV, blocked the f

40 s required for efficient deubiquitination of TRAF3 and optimal suppression of IFN-I.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

75 TRAF3 associated with Csk, promoting the dissociation of

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

77 TRAF3 autophagy is driven by RAS and results in activati

78 mediated IgG production is also increased in TRAF3 B cells.

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

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

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

82 3, but not TRAF5, to the previously reported TRAF3 binding motif in NIK.

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

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

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

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

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

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

89 city correlates with the specific binding of TRAF3, but not TRAF5, to the previously reported TRAF3 b

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

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

92 accumulation of NF-kappaB-inducing kinase in TRAF3-/- cells.

93 The adaptor and signaling proteins TRAF2, TRAF3, cIAP1 and cIAP2 may inhibit alternative nuclear f

94 In contrast to TRAF2 and TRAF3, cIAP1 and cIAP2 seem to play redundant roles in t

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

96 h TRAF3 which disrupts the formation of TBK1-TRAF3 complexes and downstream signaling responses requi

97 The formation of TBK1-TRAF3 complexes directs IRF-3 phosphorylation, and both

98 , but not PHV, blocked the formation of TBK1-TRAF3 complexes.

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

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

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

102 Furthermore, the lethality of TRAF3 deficiency in mice could be rescued by a single NI

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

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

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

106 distal signaling events were compromised by TRAF3 deficiency.

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

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

109 TRAF3-deficient B cells were also preferentially sensiti

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

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

112 lation of the canonical NF-kappaB pathway in TRAF3-deficient cells results from accumulation of NF-ka

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

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

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

116 AF3 null mutations, we generated conditional TRAF3-deficient mice.

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

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

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

120 t CD40 or BAFF receptor activation result in TRAF3 degradation in a cIAP1-cIAP2- and TRAF2-dependent

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

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

123 was associated with decreased RANKL-induced TRAF3 degradation.

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

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

126 TRAF3 from cellular lysates, and analysis of TRAF3 deletion mutants demonstrated that the TRAF3 N ter

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

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

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

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

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

132 dependent way owing to enhanced cIAP1, cIAP2 TRAF3-directed ubiquitin ligase activity.

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

134 urthermore, endogenously expressed TRAF2 and TRAF3 do not interact with K13 and play no role in K13-i

135 Degradative ubiquitination of TRAF3 during MyD88-dependent TLR signaling was essential

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

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

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

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

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

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

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

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

144 The NY-1V Gn tail coprecipitated TRAF3 from cellular lysates, and analysis of TRAF3 delet

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

146 Conversely, it recently was reported that TRAF3 functions as an essential negative regulator of th

147 to overexpression of NIK and deletion of the TRAF3 gene are implicated in human multiple myeloma.

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

149 In addition, TRAF3 has been reported to be required for K13-induced N

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

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

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

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

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

155 the protein levels of its negative regulator TRAF3 in a dose-dependent fashion.

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

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

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

159 e generated transgenic mice expressing human TRAF3 in lymphocytes.

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

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

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

163 wever, the respective functions of TRAF2 and TRAF3 in NIK degradation and activation of alternative N

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

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

166 e in modulating the degradation of TRAF2 and TRAF3 in response to signals from the TNFR superfamily.

167 ionally replace the corresponding domains of TRAF3 in suppression of the noncanonical NF-kappaB pathw

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

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

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

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

175 e roles for TRAF2, TRAF5, and TRAF6, but not TRAF3, in canonical (p50-dependent) NF-kappaB activation

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

177 Dominant-negative forms of TRAF2 and TRAF3 inhibited but did not fully block LMP1-mediated tr

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

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

180 TRAF3 interacting protein 2 (TRAF3IP2) is important for

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

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

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

184 These findings indicate that TRAF3 is a critical regulator of peripheral B cell homeo

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 an E3 ubiquitin ligase that preferentially asse

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

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

194 ecrosis factor receptor-associated factor 3 (TRAF3) is an adaptor protein that directly binds to a nu

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

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

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

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

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

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

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

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

210 ependent manner, whereas uncoupling NIK from TRAF3-mediated control causes maximal p100 processing an

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

212 The analysis of the humoral responses of the TRAF3 mice demonstrated increased responses to T-depende

213 In addition, TRAF3 mice develop autoimmunity and are predisposed to c

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

215 B-cell-specific Traf3(-/-) mice displayed severe peripheral B cell hyper

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

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

226 TRAF3 deletion mutants demonstrated that the TRAF3 N terminus is sufficient for interacting with the

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

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

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

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

231 and to circumvent the early lethal effect of TRAF3 null mutations, we generated conditional TRAF3-def

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

233 ect Hill virus (PHV) failed to coprecipitate TRAF3 or inhibit NF-kappaB or IFN-beta transcriptional r

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

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 Despite in vitro evidence that TRAF3 plays diverse roles in different cell types, littl

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

240 In this article, we provide evidence that TRAF3 potently suppresses canonical NF-kappaB activation

241 Degradation of TRAF3 prevented association of NIK with the cIAP1-cIAP2-

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

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

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

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

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

247 pon assembly of a regulatory complex through TRAF3 recruitment of NIK and TRAF2 recruitment of cIAP1

248 ermini of NS1 and NS2 did not diminish their TRAF3-reducing activity.

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

250 s factor (TNF) receptor-associated factor 3 (TRAF3) regulates both innate and adaptive immunity by mo

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

252 In summary, TRAF3 renders B cells hyperreactive to antigens and TLR

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

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

258 the lysine-63-linked polyubiquitin chains on TRAF3, resulting in its dissociation from the downstream

259 hus, our data demonstrate that inhibition of TRAF3 results in coordinated activation of both NF-kappa

260 In addition, we demonstrate that loss of TRAF3 results in profound accumulation of NF-kappaB-indu

261 s factor (TNF) receptor-associated factor 3 (TRAF3) results in constitutive noncanonical NF-kappaB ac

262 F-dependent signaling triggered noncanonical TRAF3 self-ubiquitination that activated the interferon

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

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

265 TRAF3 signaling in Treg cells was required to maintain h

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

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

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

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

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

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

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

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 mplex containing adaptor molecules TRAF2 and TRAF3, ubiquitin-conjugating enzyme Ubc13, cellular inhi

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 TRAF3 was recently identified as a tumor suppressor in h

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

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

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

292 -1V Gn cytoplasmic tail forms a complex with TRAF3 which disrupts the formation of TBK1-TRAF3 complex

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

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

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

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

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

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

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