ライフサイエンスコーパス: TRADD

1 TRADD alternatively recruits the NF-kappaB-inducing adap

2 TRADD and RIP, which bound TNFR1, did not bind DR4 and D

3 TRADD associated with wild-type LMP1 but not with isoleu

4 TRADD facilitates non-homologous end-joining (NHEJ) by r

5 TRADD has been shown to cycle between the cytoplasm and

6 TRADD is a crucial transducer for TNF-alpha-induced nucl

7 TRADD is a multifunctional signaling adaptor protein tha

8 TRADD is a TNFR1-associated signal transducer that is in

9 TRADD is required for c-Jun phosphorylation upon TNF exp

10 TRADD is specific for TRAF1 and TRAF2, which ensures the

11 TRADD knockout T cells therefore lack the appropriate pr

12 TRADD over-expression killed GM cells and activated NF-k

13 TRADD reverses these roles, employing a Pelle-like surfa

14 TRADD was also required for TRIF-dependent Toll-like rec

15 TRADD was essential for TNFR1 signaling in mouse embryon

16 TRADD was the only protein that interacted with wild-typ

17 TRADD-Fas-associated death domain protein apoptotic path

18 necrosis factor (TNF)-alpha, TNF receptor 1, TRADD, RIP, TRAF2, and NIK but does not affect IKK1- and

19 tially blocked for NF-kappaB activation by a TRADD mutant consisting of residues 122 to 293.

20 s unclear because of the unavailability of a TRADD-deficient animal model.

21 oth receptors can activate NF-kappaB using a TRADD-dependent pathway.

22 by overexpression of the downstream adaptors TRADD and FADD.

23 The signaling adaptors TRADD and RIP were also found to be necessary for ligand

24 ng-term neuronal viability in AD by allowing TRADD mediation of TNFR1 signaling in response to oxidat

25 sed comparable amounts of TNF receptor-1 and TRADD.

26 leucine-mutated LMP1 in mammalian cells, and TRADD constitutively associated with LMP1 in EBV-transfo

27 ch showed decreased DENN/MADD expression and TRADD up-regulation in the mice, compared to controls.

28 FADD and TRADD also nucleate several distal signaling complexes,

29 ARC attenuated apoptosis induced by FADD and TRADD and that triggered by stimulation of death recepto

30 tosis, indicating the importance of FADD and TRADD in Sharpin-dependent anti-apoptosis signaling in k

31 r with other DR signal transducers, FADD and TRADD participate in functional complexes assembled by c

32 mutagenesis of two death adaptors, FADD and TRADD, suggesting that a death adaptor can discriminate

33 ch are nucleated by the DD adaptors FADD and TRADD, to control cellular outcomes that range from apop

34 he death domain-containing proteins FADD and TRADD, whereas SseK3 expression resulted in weak GlcNAcy

35 FADD death domain interactions with Fas and TRADD are thought to occur on the same surface; however,

36 DENN/MADD and TRADD competitively bound to TNFR1 when overexpressed in

37 increase in TNF-alpha-induced TRADD-RIP and TRADD-TRAF2 complex formation, while interaction between

38 o death domain-containing proteins, RIP1 and TRADD.

39 Stat1 could directly interact with TNFR1 and TRADD but not with FADD.

40 HDNC induced TNF-alpha, TNFR1, and TRADD mRNA and protein expression.

41 creased constitutive expression of TNFRI and TRADD and decreased expression of TNFRII and TRAF-2 were

42 Members of this family can bind TRAF and TRADD molecules and activate NF-kappaB and AP-1, as can

43 hese results indicate that LMP1 appropriates TRADD to enable efficient long-term lymphoblastoid cell

44 D88 plays the same role in IL-1 signaling as TRADD and Tube do in TNF and Toll pathways, respectively

45 rmitting the recruitment of proteins such as TRADD and TRAF2 to the active TNF-R1 signaling complex.

46 eptors such as Fas or other adapters such as TRADD, whereas the FADD death effector domain binds to p

47 In transfection assays, TRADD and TES2 synergistically mediated high-level NF-ka

48 DD signaling cascades appear to bifurcate at TRADD.

49 complex formation, while interaction between TRADD and FADD was unaffected.

50 avage products, enhanced interaction between TRADD and FADD/MORT1 and increased cells' sensitivity to

51 ily of proteins, and the other (CTAR2) binds TRADD, suggesting that LMP1 transduces signals similarly

52 ing that inflammation is primarily driven by TRADD- and FADD-dependent keratinocyte apoptosis while n

53 Conversely, apoptosis induced by TRADD in the cytoplasm is resistant to Bcl-xL, but sensi

54 TRAF2 signaling is more readily initiated by TRADD than by direct receptor-TRAF2 interactions.

55 1 to TNF-R1 is TNF-dependent, is mediated by TRADD, and is independent of TNF-R2.

56 complex, and RIP1 recruitment is mediated by TRADD.

57 serine-threonine kinase that is recruited by TRADD to TNFR1 in a TNF-dependent process.

58 formation of a signaling complex containing TRADD, RIP1, Nox1, and the small GTPase Rac1.

59 mation of a DR3 signaling complex containing TRADD, TRAF2, and RIP and activated the NF-kappaB and th

60 Conversely, TRADD, TNFR1, and activated JNK were increased.

61 Here we demonstrate that cytoplasmic TRADD translocates to DNA double-strand break sites (DSB

62 membrane and subsequently induced cytosolic TRADD-Fas-associated death domain protein complex.

63 factor (TRAF), TNFR associated death domain (TRADD) and Fas-associated death domain (FADD).

64 TNF receptor-associated death domain (TRADD) is an essential mediator of TNF receptor signalin

65 or receptor (TNFR)1-associated death domain (TRADD) plays an essential role in recruiting signaling m

66 The TNFR-associated death domain (TRADD) protein has been suggested to be a crucial signal

67 DENN/MADD, and TNFR-associated death domain (TRADD) protein in AD-affected tissues and cell cultures.

68 1 (TNFR1) and TNFR-associated death domain (TRADD) protein of the cell membrane.

69 sis factor receptor-associated death domain (TRADD) protein, or RIP1.

70 sis factor receptor-associated death domain (TRADD) was reduced in androgen deprivation-independent c

71 TNF receptor (TNFR)-associated death domain (TRADD), and caspases.

72 FADD), TNFRSF1A-associated via death domain (TRADD), and receptor-interacting serine/threonine protei

73 by DN-TNF receptor-associated death domain (TRADD), DN-TNF receptor-associated factor (TRAF)2, DN-re

74 IP1 to TNFRSF1A-associated via death domain (TRADD), two crucial signal adaptors for NF-kappaB activa

75 receptor 1 (TNFR1)-associated death domain (TRADD)-dependent TNFR1 signaling in epidermal keratinocy

76 In these structures, the TRADD death domain (TRADD-DD) can activate an apoptosis pathway that is mech

77 Knocking down TRADD expression in LNCaP cells impaired TNF-alpha-induc

78 otide (ASO)-mediated depletion of endogenous TRADD on TNF induction of inflammation-related gene prod

79 el with this observation, WOX1 also enhanced TRADD (TNF receptor-associated death domain protein)-med

80 Conversely, stable expression of exogenous TRADD enhanced radiation-induced apoptosis of GM cell li

81 In the absence of export, TRADD is found within nuclear structures that are associ

82 TNFR1 signaling factors TRADD and Fas-associated death domain protein (FADD) wer

83 Thus, both DR5 and DR4 use FADD, TRADD, and RIP in their signal transduction pathways, an

84 ally, both receptors can interact with FADD, TRADD, and RIP.

85 LMP1 Y(384)YD(386), which are required for TRADD and RIP1 binding and for NF-kappaB activation, wer

86 Using T cells from TRADD knockout mice, we demonstrate in this study that t

87 By generating TRADD-deficient mice, we found here that TRADD serves an

88 However, no mutations in candidate genes (TRADD, CDH5, CDH8 and CDH11) were detected.

89 Seven proteins were identified, including TRADD, TRAP2, and TRAF2, which are three proteins known

90 intracellular signaling molecules including TRADD, TRAF2, FADD, and FLICE.

91 We found reduced DENN/MADD and increased TRADD expression immunohistochemically in the hippocampu

92 ed an apparent increase in TNF-alpha-induced TRADD-RIP and TRADD-TRAF2 complex formation, while inter

93 DD may therefore be protective by inhibiting TRADD-induced apoptotic cell death.

94 Interestingly, TRADD is dispensable, while RIP is required for TNF-indu

95 hich mPLK/IRAK mediates this TNF response is TRADD- and TRAF2-independent.

96 rmed by the interactions between RIP kinase, TRADD, FADD and RAIDD - adaptor proteins that contain de

97 e molecular interactions through which LMP1, TRADD, and RIP participate in B-lymphocyte activation an

98 induces the formation of a nuclear-localized TRADD-STAT1-alpha complex.

99 In current models, TRADD recruits RIP, TRAF2, and FADD to activate NF-kappa

100 ), or binding of the TNF-R1 adapter molecule TRADD.

101 cifically with the TNFR1-associated molecule TRADD.

102 FR-associated death domain adaptor molecule (TRADD), the Fas-associated death domain adaptor molecule

103 ment of the death domain signaling molecules TRADD and RIP to the receptor signaling complex.

104 The N-terminal domain (N-TRADD) promotes the recruitment of TRAF2 to TNFR1 by bin

105 The solution structure of N-TRADD was determined, revealing a novel protein fold.

106 o help identify the site of interaction of N-TRADD with C-TRAF2, providing a framework for future att

107 Although morphologically normal, TRADD-deficient mice were resistant to toxicity induced

108 to DNA damage, which is reversed by nuclear TRADD expression.

109 Apoptosis by nuclear TRADD-DD is promyelocytic leukemia protein dependent, in

110 However, the underlying function of nuclear TRADD is poorly understood.

111 Moreover, in the absence of TRADD, both the stimulation of MAPK signaling and activa

112 nsmission of TNFR1 signals in the absence of TRADD.

113 ations affecting the different activities of TRADD do not map to discrete regions but rather are spre

114 The biological activities of TRADD have been mapped to a 111-amino acid region within

115 The association of TRADD, a 34-kDa cytoplasmic protein containing a C-termi

116 pitation demonstrates competitive binding of TRADD and RIP to TNFR1, whereas TRAF2 recruitment requir

117 intracellular signaling complex comprised of TRADD, RIP1, TRAF2, and AIPl.

118 However, cells with a genetic deficiency of TRADD are unavailable, precluding analysis with mature i

119 Deficiency of TRADD or its sequestration in cytosol leads to accumulat

120 We further show that knock-down of TRADD enhances IFN-gamma signaling to increase OIP-1 gen

121 Casper, and caspase-8 function downstream of TRADD and contribute to TNF-R1-induced NF-kappaB activat

122 Elevated expression of TRADD in cells triggers both NF-kappaB activation and pr

123 itively establish the biological function of TRADD in TNF signaling.

124 expression resulted in weak GlcNAcylation of TRADD but not FADD.

125 ts indicate usage of antisense inhibitors of TRADD expression for modulating diseases associated with

126 s a consequence of ASO-mediated knockdown of TRADD.

127 Finally, an impaired nuclear localization of TRADD triggers cell death through the persistent activat

128 ain as well as S215LKD and S296LAE motifs of TRADD-death domain) are phosphorylated, and this is requ

129 performed an alanine scanning mutagenesis of TRADD's death domain to explore the relationship among i

130 generation with dominant-negative mutants of TRADD or Rac1, as well as knockdown of Nox1 using siRNA,

131 ceptor repression, whereas overexpression of TRADD in C4-2B cells restored their sensitivity to TNF-a

132 A broader perspective of TRADD's role in TNF signaling was indicated by microarra

133 ls to TL1A is dependent upon the presence of TRADD.

134 lf-association and subsequent recruitment of TRADD in the signaling activity of TNFR-1.

135 Furthermore, TNF-dependent recruitment of TRADD to surface TNFR1 was also inhibited.

136 factor (TNF) binding leads to recruitment of TRADD to TNFR1.

137 Restoration of TRADD in Tradd(-/-) MEFs restores TRAIL resistance, indi

138 definitively establish an essential role of TRADD in DR3 signaling.

139 However, the role of TRADD in other death receptor (DR) signaling pathways, i

140 e plasmids, we also demonstrated the role of TRADD, TRAF2, NIK and Ras in EGF-induced NF-kappaB activ

141 indicate that nucleocytoplasmic shuttling of TRADD leads to the activation of distinct apoptosis mech

142 s, reflecting the biological significance of TRADD regulation in p53-independent apoptosis.

143 The C-terminal of TRADD comprises the "death domain" that is responsible f

144 , our findings suggest that translocation of TRADD to DSBs into the nucleus contributes to cell survi

145 anscription by binding to TRAFs, JAK3 and/or TRADD.

146 of its death motifs to engage either CD95 or TRADD.

147 Depletion of FADD or TRADD in Sharpin-deficient HaCaT cells suppressed TNF-in

148 hysiological function of the adaptor protein TRADD remains unclear because of the unavailability of a

149 eptors or indirectly via the adaptor protein TRADD.

150 MORT1 or the TNF receptor-associated protein TRADD [2-4].

151 A TNF-R1-associated protein TRADD has been discovered that interacts with the death

152 or 1 (TNFR1)-associated death domain protein TRADD to mediate NF-kappaB and c-Jun N-terminal kinase a

153 ts interaction with the death domain protein TRADD.

154 h the TNFRI death domain interacting protein TRADD.

155 for optimal binding of the scaffold protein TRADD to the activated TNFalpha receptor through both ki

156 NF-receptor-associated death domain protein (TRADD) and receptor-interacting protein-1 (RIP1) in TRAI

157 NF receptor-associated death domain protein (TRADD) in a ligand-independent manner.

158 and TNF-R1-associated death domain protein (TRADD) intracellularly, although it can be detected at l

159 TNFR-associated death domain protein (TRADD) is a key effector protein of TNFR1 signaling.

160 receptor 1-associated death domain protein (TRADD) is an adaptor protein known to be involved in the

161 r 1 (TNFR1)-associated death domain protein (TRADD) is essential in recruiting signaling molecules to

162 or receptor-associated death domain protein (TRADD) to FADD to FLICE, whereas for CD-95 the receptor

163 r 1 (TNFR1)-associated death domain protein (TRADD), a death adaptor essential for TNFR1-dependent si

164 TNFR1, TNFR-associated death domain protein (TRADD), Fas-associated death domain protein, and recepto

165 ) and TNFR1-associated death domain protein (TRADD), suggesting that the core protein does not pertur

166 luding TNFR-associated death domain protein (TRADD), TNFR-associated factor 2 (TRAF-2), and receptor

167 ruits TNFR1-associated death domain protein (TRADD), which in turn triggers two opposite signaling pa

168 duced TNFR1-associated death domain protein (TRADD)-dependent hepatocyte apoptosis and liver tumors i

169 or receptor-associated death domain protein (TRADD).

170 or molecular weights of the adaptor proteins TRADD (TNF receptor-associated death domain), RIP (recep

171 here it associated with the adaptor proteins TRADD (TNF receptor-associated death domain), TNF recept

172 the death domain-containing adaptor proteins TRADD and FADD.

173 ment of TNFR1 recruited the adaptor proteins TRADD, TRAF-2, and RIP into lipid rafts and activated Rh

174 nd the TNFR-associated death domain proteins TRADD and RIP, thereby activating NF-kappaB and c-Jun N-

175 ization of death domain containing proteins (TRADD, FADD/MORT-1, RIP), TRAF domain containing protein

176 the recruitment of at least three proteins (TRADD, RIP, and TRAF2) to the type 1 TNF-alpha receptor

177 t in response to H2O2, the adapter proteins, TRADD and TRAF2, and JNK were recruited to the receptor.

178 s crmA and BD-fmk partially inhibit TNF-R1-, TRADD, and TNF-induced NF-kappaB activation, suggesting

179 rylation was prolonged in cells with reduced TRADD expression.

180 , we found that androgen deprivation reduces TRADD expression in vitro and in vivo, suggesting that a

181 elopment of TNF-alpha resistance by reducing TRADD expression during prostate cancer progression.

182 Further, LMP1 does not require TRADD residues 294 to 312 for NF-kappaB activation, whil

183 to TNFR1, whereas TRAF2 recruitment requires TRADD.

184 r NF-kappaB activation, while TNFR1 requires TRADD residues 296 to 302.

185 We circumvented this problem by silencing TRADD expression with small interfering RNA.

186 nus that lies between the TES1-TRAF and TES2-TRADD and -RIP binding sites, an EBV recombinant was mad

187 Such observations provide evidence that TRADD performs an obligate role in TNF-induced NF-kappaB

188 We found that TRADD is required for TNFR1 to induce NF-kappaB activati

189 ing TRADD-deficient mice, we found here that TRADD serves an important function in tumor necrosis fac

190 These data indicate that TRADD may be involved in IFN-gamma signaling by forming

191 ADD to the receptor complex, indicating that TRADD may limit FADD binding within the receptor complex

192 s restores TRAIL resistance, indicating that TRADD plays a survival role in TRAIL signaling.

193 Our data also show that TRADD and RIP1 compete for recruitment to the TNFR1 sign

194 Here we show that TRADD contains a nuclear export and import sequence that

195 Here we show that TRADD directly interacts with TRAF2 and FADD, signal tra

196 Here, we show that TRADD interacts strongly with RIP, another death domain

197 We show that TRADD is recruited to the TRAIL-receptor complex, and RI

198 using overexpression systems suggested that TRADD is recruited to the DR3 complex in response to the

199 We found that blocking the TRADD-mediated pathway using a dominant-negative mutant

200 ell killing from NF-kappaB activation by the TRADD death domain has been identified indicating that t

201 resence and transcriptional potential in the TRADD knockdown cells.

202 Additionally, one of the TRADD mutants that fails to activate NF-kappaB was found

203 We now report the structure of the TRADD-TRAF2 complex, which is highly distinct from recep

204 onger affinity and unique specificity of the TRADD-TRAF2 interaction are crucial for the suppression

205 egion in the cytoplasmic tail of CD40 or the TRADD-interacting domain of LMP1 signal on the JNK axis

206 In these structures, the TRADD death domain (TRADD-DD) can activate an apoptosis

207 ivation of NF-kappaB is mediated through the TRADD-TRAF2-RIP-TAK1-IKK pathway, making TNF a novel tar

208 in self-association and interaction with the TRADD death domain.

209 eas TNFR1 consistently co-localized with the TRADD, FADD, the caspase-8, and TRAF2 in the cytosolic f

210 HCV core protein does not interfere with the TRADD-Fas-associated death domain protein (FADD)-procasp

211 whereas TNFR1 binds FADD indirectly, through TRADD.

212 F7 activation, implicating signaling through TRADD and RIP1 in IRF7 activation.

213 We now find that LMP1 signaling through TRADD differs from TNFR1 signaling through TRADD.

214 h TRADD differs from TNFR1 signaling through TRADD.

215 F-kappaB reporter activity induced by TNFR1, TRADD, TRAF2, NIK, and IKK but not that induced by p65 t

216 F-kappaB reporter activity induced by TNFR1, TRADD, TRAF2, NIK, and IKK but not that induced by p65 t

217 F-kappaB reporter activity induced by TNFR1, TRADD, TRAF2, NIK, TAK1/TAB1, and IKK-beta.

218 The NF-kappaB activation induced by TNFR1, TRADD, TRAF2, NIK, TAK1/TAB1, and IKKbeta was also inhib

219 ter gene expression activated by TNF, TNFR1, TRADD, TRAF2, NF-kappaB-inducing kinase, IkappaBalpha ki

220 NF-kappaB activation induced by TNF, TNFR1, TRADD, TRAF2, NIK, and I kappaB alpha kinase was modulat

221 ter gene expression activated by TNF, TNFR1, TRADD, TRAF2, NIK, and IKK but not that activated by the

222 ter gene expression activated by TNF, TNFR1, TRADD, TRAF2, NIK, and IKK but not that activated by the

223 ter gene expression activated by TNF, TNFR1, TRADD, TRAF2, NIK, and IKK but not that activated by the

224 er gene transcription induced by TNF, TNFR1, TRADD, TRAF2, NIK, and IKK was also blocked by guggulste

225 er gene transcription induced by TNF, TNFR1, TRADD, TRAF2, TAK1, receptor-interacting protein, NIK, a

226 lated, and this is required for stable TNFR1-TRADD complex formation and subsequent activation of NF-

227 we show that Stat1 is involved in the TNFR1-TRADD signaling complex, as determined by employing a no

228 Thus, these two TNFR1-TRADD signaling cascades appear to bifurcate at TRADD.

229 RK(13) cells, L,D-MDP up-regulated the TNFR1.TRADD complex of the plasma membrane and subsequently in

230 , with DENN/MADD abrogating TNFR1 binding to TRADD.

231 binding to Fas but do not affect binding to TRADD.

232 n-protein interactions for FADD complexes to TRADD complexes reveals that FADD uses a Tube-like surfa

233 phospho-S296LAE motifs are also critical to TRADD for recruiting Fas-associated death domain protein

234 soluble TNFSF15; soluble TNFSF15 then led to TRADD/FADD/MALT-1- and caspase-8-mediated autocrine IL-1

235 to the plasma membrane, where it binds TRAF, TRADD, and JAK molecules to activate NF-kappaB-, AP-1-,

236 The domain of LMP-1 that binds TRAF, TRADD, and JAK/STAT molecules is not required for this r

237 tutive association with TRAF1, TRAF2, TRAF3, TRADD, and RIP.

238 we found that following radiation treatment, TRADD expression was induced in a uniquely radiosensitiv

239 Unsurprisingly, TRADD is required for recruitment of receptor interactin

240 hese findings generate interest in utilizing TRADD in gene therapy for GM tumors, particularly in lig

241 of TNF receptor 2 (TNFR2) or indirectly, via TRADD, to the intracellular region of TNF receptor 1 (TN

242 r factors 53BP1 and Ku70/80 complex, whereas TRADD is dispensable for homologous recombination (HR) r

243 f complex II following TNF exposure, whereas TRADD KD allows efficient RIP-caspase 8 association.

244 sion for modulating diseases associated with TRADD-dependent signal transduction pathways.

245 titutes for RIP and directly associates with TRADD in TNF receptor complexes following TNF-alpha stim

246 veolin-1 complex transiently associates with TRADD, and upon overexpression of TNFR2, the TRAF2-caveo

247 Despite constitutive association with TRADD or RIP, LMP1 does not induce apoptosis in EBV-nega

248 activate NF-kappaB through association with TRADD, RIP, and TRAF2; activation of the NF-kappaB-induc

249 h domain, the site of TNFR1 association with TRADD.

250 at these two signaling pathways diverge with TRADD.

251 assays revealed that TRUSS can interact with TRADD, TRAF2, and components of the IKK complex.

252 al for self-interaction and interaction with TRADD.

253 R-induced NF-kappaB activation, but not with TRADD, an adaptor protein which serves to recruit RIP to

254 cids to activate NF-kappaB or synergize with TRADD in NF-kappaB activation, while TNFR1 requires appr