ライフサイエンスコーパス: MALT1

1 enotype with that of MALT1 knockout animals (Malt1(-/-)).

2 mphoid tissue lymphoma-translocation gene 1 (MALT1).

3 e-1 proteins were cleaved by the paracaspase MALT1.

4 adaptor molecule BCL10, and the paracaspase MALT1.

5 ilitates the association of Carma1 with Bcl0-Malt1.

6 D is associated with homozygous mutations in MALT1.

7 on after activation, 2 events that depend on MALT1.

8 and mechanism of paracaspases exemplified by MALT1.

9 f helix 5 of the Bcl10 CARD directly contact MALT1.

10 s activation is dependent on the paracaspase MALT1.

11 ting with the immunoglobulin-like domains of MALT1.

12 that is independent of PKCtheta, Bcl10, and Malt1.

13 and cIAP2) fused to C-terminal sequences of MALT1.

14 three principal proteins, CARMA3, Bcl10, and MALT1.

15 or the generation of a fusion protein, cIAP2-MALT1.

16 harmacological inhibition of the CBM protein MALT1.

17 elated diseases associated with mutations in MALT1.

18 -kappaB signalling related factors HMGA1 and MALT1.

19 lective, as shown by the fact that it spared Malt1, a direct Bcl10 binding partner.

20 pment was restored by compound deficiency of MALT1, a key downstream component of TCR signaling in T

21 ubiquitin binding by the Ig3 domain promotes MALT1 activation by an allosteric mechanism that is esse

22 ed interfaces in Bcl10 filament assembly and MALT1 activation in vitro and NF-kappaB activation in ce

23 MALT1 activation requires its monoubiquitination on lysi

24 We developed a MALT1 activity assay and identified chemically diverse M

25 (Treg)-cell development, while dysregulated MALT1 activity can lead to lymphoma.

26 y of the CARMA1-BCL10-MALT1 complex, wherein MALT1 acts as (a) a scaffold to recruit components of th

27 The CARMA1-Bcl10-Malt1 adaptor complex regulates NFkappaB activation by a

28 the successful pharmacological validation of MALT1 allosteric inhibition in preclinical models of hum

29 tivation-associated aggregation of Bcl10 and Malt1 also demonstrate both digital behavior and high co

30 However, it remains unclear which role MALT1, an essential component of the CARD11-BCL10-MALT1

31 lack of caspase-8 results in the absence of MALT1 and Bcl-10 in the active caspase complex.

32 nstrated that GRK2 binds the death domain of MALT1 and inhibits MALT1 scaffolding and proteolytic act

33 function as a tumor suppressor by inhibiting MALT1 and provide a roadmap for developing new strategie

34 LT1 translocations having high expression of MALT1 and RARA, samples with plasmacytic differentiation

35 probes leads to improved selectivity toward MALT1 and results in cell-permeable fluorescent probes.

36 ting signaling related polyubiquitination of Malt1 and Stat3, leading to NF-kB activation and RORgamm

37 d compound, MI-2, featured direct binding to MALT1 and suppression of its protease function.

38 ow provide evidence that the death domain of MALT1 and the CARD of Bcl10 also contribute to Bcl10-MAL

39 We found that MALT1(-/-) and MALT1(PD/PD) mast cells are equally impai

40 rrow-derived mast cells from MALT1 knockout (MALT1(-/-)) and MALT1 protease-deficient (MALT(PD/PD)) m

41 oid tissue lymphoma translocation protein 1 (MALT1), and caspase recruitment domain-containing (CARD)

42 phocyte defects, are associated with CARD11, MALT1, and BCL10 deficiencies.

43 inked and K29-linked polyubiquitin chains on Malt1, and K27-linked polyubiquitin chains on Stat3.

44 in that nucleates a complex including BCL10, MALT1, and other IkappaB kinase (IKK)-signalosome compon

45 o the binding of cofactors, including Bcl10, MALT1, and the HOIP catalytic subunit of the linear ubiq

46 quires Bcl10 lysines 17, 31, and 63, CARD11, MALT1, and the HOIP subunit of the linear ubiquitin chai

47 with B cell lymphoma 10 (BCL10), paracaspase MALT1, and the inhibitors of kappaB kinase (IKK) complex

48 eral, immune defects were more pronounced in Malt1(-/-) animals.

49 While both BCL10 and MALT1 are critically involved in antigen receptor-mediat

50 Bcl10 and MALT1 are essential mediators of NF-kappaB activation in

51 e paracaspase (protease related to caspases) MALT1 as critical intermediates linking the TCR to the I

52 API2 moiety mediates oligomerization of API2-MALT1 as well as interaction with tumor necrosis factor

53 we show that a subset of MCLs is addicted to MALT1, as its inhibition by either RNA or pharmacologic

54 nents of the CBM complex, Carma3, Bcl10, and Malt1, as key mediators of the CXCL8/IL8-induced NFkappa

55 interacting protein-1 (RIP1) as a novel API2-MALT1-associated protein, and demonstrate that RIP1 is r

56 ne and somatic gain-of-function mutations of MALT1, BCL10, and CARD11 have also been found in patient

57 IP, and IKKalpha/beta/gamma but also CARMA1, MALT1, BCL10, and PKC, molecules previously shown to reg

58 B cell lymphoma (DLBCL), engages the CARD11-MALT1-BCL10 (CBM) adapter complex to activate IkappaB ki

59 e (ie, IKK-alpha,-beta,-gamma/NEMO and CARMA/MALT1/Bcl10 complex) are present in anucleate platelets

60 Studies of c-IAP2/MALT1 BIR1 mutant (E47A/R48A) that fails to activate NF-

61 Knocking down both HMGA1 and MALT1 by RNAi had a silencing effect on NF-kappaB-respon

62 eover, individuals with inherited defects of MALT1, CARD9, and CARD11 present with immunological and

63 ot required for assembly of the CARMA1/Bcl10/Malt1 (caspase-recruitment domain (CARD) membrane-associ

64 f a scaffold consisting of CARD9, BCL10, and MALT1 (CBM complex) is critical for effective signaling

65 ein complex that contains CARMA1, BCL10, and MALT1 (CBM complex).

66 hat requires the triad of CARMA3, Bcl10, and MALT1 (CBM signalosome).

67 P9X interacts with Bcl10 of the Carma1-Bcl10-Malt1 (CBM) complex and removes the TCR-induced ubiquiti

68 The mechanism by which the Carma1-Bcl10-MALT1 (CBM) complex couples T cell antigen receptor (TCR

69 However, the Card11-Bcl10-Malt1 (CBM) complex that is essential for TCR activation

70 The CARMA1/Bcl10/Malt1 (CBM) complex, comprised of adaptors that link the

71 These 3 CARD-BCL10-MALT1 (CBM) complexes activate nuclear factor kappaB in

72 w that, after disruption of the CARMA1-BCL10-MALT1 (CBM) signalosome complex, most tumour-infiltratin

73 nical NF-kappaB pathway via the CARD11/BCL10/MALT1 (CBM) signalosome involving key, yet ill-defined r

74 The CARMA1/Bcl10/MALT1 (CBM) signalosome mediates antigen receptor-induce

75 theta-dependent assembly of the CARMA1-BCL10-MALT1 (CBM) signalosome, which coordinates downstream ac

76 mphoid tissue lymphoma translocation gene 1 (MALT1 [CBM]) signalosome complex.

77 (Bcl10)-mucosa-associated lymphatic tissue 1(MALT1) (CBM) complex, which appears to be independent of

78 MALT1 cleavage activity is linked to the pathogenesis of

79 The paracaspase MALT1 cleaves and removes negative checkpoint proteins,

80 hich requires signals from the CARD11-BCL-10-MALT1 (CMB) complex.

81 Genetic deficiencies of either BCL10 or MALT1 completely rescued the phenotype, and pharmacologi

82 With the identification of the CARMA1-BCL10-MALT1 complex and ongoing progress in understanding the

83 ing stimuli that require correct CARMA-BCL10-MALT1 complex formation and functioning.

84 A recent study reveals that the Bcl10-Malt1 complex promotes mast-cell interleukin-6 and tumor

85 , an essential component of the CARD11-BCL10-MALT1 complex that links BCR signaling to the NF-kappaB

86 TCR-stimulated assembly of the CARMA1-BCL-10-MALT1 complex was substantially impaired in the absence

87 lation promotes assembly of the CARMA1-BCL10-MALT1 complex, wherein MALT1 acts as (a) a scaffold to r

88 NF-kappaB signaling through the CARD11-BCL10-MALT1 complex.

89 ta strongly suggest that the death domain of MALT1 contributes significantly to the association betwe

90 following MALT1 inhibition demonstrated that MALT1 controls an MYC-driven gene expression network pre

91 nally, non-degradative polyubiquitination of Malt1, critical for NF-kappaB activation and Th17 cell f

92 Although a direct interaction between the MALT1 death domain and Bcl10 cannot be detected via immu

93 Mechanistically, MALT1 deficiency abolished both NF-kappaB and STAT3 acti

94 In contrast, Malt1 deficiency did not affect Th1 cells.

95 In comparison, MALT1 deficiency does not affect tumor progression in a

96 -kappaB activation in cancer cells, and that MALT1 deficiency impaired EGFR-induced NF-kappaB activat

97 Adoptive transfer experiments showed that MALT1 deficiency in splenocytes is sufficient for EAE re

98 Using Bcl10- and MALT1-deficient cells, we show that CARD11 can recruit s

99 ficient T cells, suggesting the inability of MALT1-deficient effector T cells to induce demyelinating

100 MALT1-deficient mice show significantly less lung tumor

101 tor-kappaB activation and IL-2 production in MALT1-deficient mouse T cells.

102 during EAE, which was partially impaired in MALT1-deficient T cells, suggesting a contribution of MA

103 e T cell activation was severely impaired in MALT1-deficient T cells, suggesting the inability of MAL

104 The unique enzymatic activity of MALT1 degrades one of its binding partners, BCL-10, as w

105 iquitination as a critical component of API2-MALT1-dependent lymphomagenesis.

106 map for developing new strategies to inhibit MALT1-dependent lymphomagenesis.

107 s-associated genes that are upregulated in a MALT1-dependent manner after PAR1 stimulation in cancer

108 To further access a physiological role of MALT1-dependent NF-kappaB activation in EGFR-driven tumo

109 cellular and genetic evidence that suggests MALT1-dependent NF-kappaB activation is important in EGF

110 RAF2 binding both contribute to maximal API2-MALT1-dependent NF-kappaB stimulation.

111 or activate NF-kappaB, indicating that API2-MALT1-dependent RIP1 ubiquitination represents a gain of

112 MALT1 diminishes the activation of apoptotic effector ca

113 sequent spleen tyrosine kinase 2-CARD9/BCL10/MALT1-driven signaling cascade, impairing nuclear factor

114 complex comprised of CARMA3, Bcl10, and the MALT1 effector protein (CBM complex).

115 step for the maximal activation of HOIP and MALT1 enzymatic activity after cofactor recruitment to C

116 Here, we induced MALT1 expression in mouse Sca1(+)Lin(-) hematopoietic st

117 ymphomas can be modeled in mice by targeting MALT1 expression to hematopoietic stem/progenitor cells,

118 lung cancer was developed in the absence of MALT1 expression.

119 ARD11), mucosa-associated lymphoid tissue 1 (MALT1) for combined immunodeficiencies, and tetratricope

120 We demonstrate that the API2-MALT1 fusion oncoprotein created by the recurrent t(11;1

121 The API2-MALT1 fusion oncoprotein is created by the recurrent t(1

122 )(q21;q21) translocation creating the c-IAP2.MALT1 fusion protein activates NF-kappaB and contributes

123 The c-IAP2.MALT1 fusion protein associates with TRAF1 and TRAF2 usi

124 The c-IAP2.MALT1 fusion protein constitutively activates the NF-kap

125 , primary MALT lymphomas harbouring the API2-MALT1 fusion uniquely demonstrate LIMA1 cleavage fragmen

126 Chromosomal translocations involving the MALT1 gene are hallmarks of mucosa-associated lymphoid t

127 The function of the MALT1 gene is subverted by oncogenic chimeric fusions ar

128 e strongest signal is in the promoter of the MALT1 gene, involved in insulin and glycaemic pathways,

129 hanism by which monoubiquitination activates MALT1 had remained elusive.

130 Our data suggest MALT1 has an ancient role modulating neural circuit func

131 As such, MALT1 has emerged as a potential pharmaceutical target.

132 The paracaspase MALT1 has gained increasing interest as a target for the

133 In this capacity, MALT1 has two functions, acting as a scaffolding protein

134 Chemical tools that detect active MALT1 have been reported, but suffer from poor cell perm

135 d CARD11 and the 2 core components BCL10 and MALT1, have recently been reported.

136 tive WT Th cells successfully induced EAE in Malt1-/- hosts.

137 r cells, demonstrating the oncogenic role of MALT1 in lymphomagenesis.

138 ctively inhibits the proteolytic activity of MALT1 in NF-kappaB-dependent assays.

139 tes a unique signaling cascade via Bcl10 and Malt1 in NK cells.

140 icantly to the association between Bcl10 and MALT1 in T cells in vivo.

141 We studied the role of MALT1 in the development of experimental autoimmune ence

142 in a mouse model (LSL-K-ras(G12D); CCSP-Cre; Malt1(-/-)) in which lung cancer is induced by expressin

143 ic mouse model (tetO-EGFR(L858R); CCSP-rtTA; Malt1(-/-)), in which mutant EGFR-driven lung cancer was

144 The paracaspase domain of MALT1, in a protease-independent manner, induces caspase

145 Intriguingly, whereas degranulation is MALT1-independent, MALT1(PD/PD) mice are protected from

146 Treatment of MALT1-induced lymphomas with a specific inhibitor of MAL

147 However, the mechanisms underlying API2-MALT1-induced MALT lymphomagenesis are not fully underst

148 mouse splenocytes, we could demonstrate that MALT1-induced MYC regulation is not restricted to MCL, b

149 we investigated the role of TRAF2 in c-IAP2/MALT1-induced NF-kappaB activation.

150 Here we show that API2-MALT1 induces paracaspase-mediated cleavage of the tumou

151 Gene expression profiling following MALT1 inhibition demonstrated that MALT1 controls an MYC

152 Functionally, MALT1 inhibition shows significant defects in EGFR-assoc

153 al rationale for the clinical development of MALT1 inhibitors in CLL, in particular for ibrutinib-res

154 olleagues and Fontan and colleagues describe MALT1 inhibitors suitable for clinical use that are sele

155 ABC-DLBCL, and provides mouse models to test MALT1 inhibitors.

156 vity assay and identified chemically diverse MALT1 inhibitors.

157 ines, a class of highly selective allosteric MALT1 inhibitors.

158 in-coupled receptor kinase 2 (GRK2) as a new MALT1-interacting protein.

159 Moreover, the Bcl10-MALT1 interaction is the second reported example of inte

160 d the CARD of Bcl10 also contribute to Bcl10-MALT1 interactions.

161 ding of the Bcl10 CARD strongly impair Bcl10-MALT1 interactions.

162 Loss of Malt1 interfered with expression of the Th17 effector cy

163 trate that the association between Bcl10 and MALT1 involves a complex interaction between multiple pr

164 Our results indicate that MALT1 is a central, cell-intrinsic factor that determine

165 The paracaspase Malt1 is a key regulator of canonical NF-kappaB activati

166 contain caspase recruitment domains (CARDs), MALT1 is a paracaspase with structural similarity to cas

167 MALT1 is also required for NF-kappaB-dependent induction

168 LIMA1 binding by API2-MALT1 is API2 dependent and proteolytic cleavage is depe

169 Constitutive proteolytic activity of MALT1 is associated with highly aggressive B-cell lympho

170 By regulating linear ubiquitination, MALT1 is both a positive and negative pleiotropic regula

171 The catalytic activity of the protease MALT1 is required for adaptive immune responses and regu

172 h its heterozygous controls, suggesting that MALT1 is required for the progression of EGFR-induced lu

173 MALT1 is the only known paracaspase and is a critical me

174 MALT1 is thought to function as a scaffold and protease

175 oid tissue lymphoma translocation protein 1 (MALT1) is intact in our series, arguing against its invo

176 nd that mucosa-associated lymphoid tissue 1 (MALT1) is involved in EGFR-induced NF-kappaB activation

177 small molecule inhibitor of the para-caspase MALT1, is effective in preclinical models of another typ

178 Moreover, Stat3 K180 and Malt1 K648 are targeted by Hectd3 for non-degradative po

179 ancer, which is suppressed by siRNA-mediated MALT1 knockdown, suggesting that an intact CBM complex i

180 compared bone marrow-derived mast cells from MALT1 knockout (MALT1(-/-)) and MALT1 protease-deficient

181 )) and compared their phenotype with that of MALT1 knockout animals (Malt1(-/-)).

182 hat CD4(+) T cells from PKCtheta, Bcl10, and Malt1 knockout mice show severe impairment of proliferat

183 which can be blocked by CRISPR/Cas9-mediated MALT1 knockout.

184 MALT1-knockout mice did not develop any clinical symptom

185 iltration into the spinal cord was absent in MALT1-knockout mice, as were demyelination and proinflam

186 cIAP2-MALT1 lacks E3 activity, and concomitantly, the BCL10 pr

187 associated with low miR-26 and high HMGA1 or MALT1 levels and not with levels of any of them individu

188 ex of proteins containing CARMA3, Bcl10, and MALT1 links PAR-1 activation to stimulation of the Ikapp

189 g association between peanut allergy and the MALT1 locus in LEAP participants in the peanut avoidance

190 MALT1 mainly functions as a scaffold protein by recruiti

191 , mice deficient for the NF-kappaB regulator MALT1 (Malt1-/- mice) exhibit strong lymphocytic infiltr

192 Together, our data indicate that MALT1 may be an interesting therapeutic target in the tr

193 hat TRAF2 interaction is critical for c-IAP2/MALT1-mediated increases in the NF-kappaB activity, incr

194 Intriguingly, API2-MALT1-mediated proteolysis generates a LIM domain-only (

195 MALT1 mediates Ag-induced signaling to the transcription

196 MALT1 mediates signaling from many immune receptors in m

197 sue lymphoma-translocation gene 1-deficient (Malt1(-/-)) mice.

198 deficient for the NF-kappaB regulator MALT1 (Malt1-/- mice) exhibit strong lymphocytic infiltration i

199 g the concerted actions of both the API2 and MALT1 moieties of the fusion.

200 PI2 moiety of one monomer interacts with the MALT1 moiety of another monomer.

201 The molecular requirements for MALT1 monoubiquitination and the mechanism by which mono

202 e BIR domains of c-IAP2 with the paracaspase/MALT1 (mucosa-associated lymphoid tissue) protein, a cri

203 e compare B cells from the only known living MALT1(mut/mut) patient with healthy MALT1(+/mut) family

204 n living MALT1(mut/mut) patient with healthy MALT1(+/mut) family members using 10-plex Tandem Mass Ta

205 rast to wild-type human MALT1, the patients' MALT1 mutant failed to correct defective nuclear factor-

206 /MALT1 oncoprotein and BIR1 E47A/R48A c-IAP2/MALT1 mutant that cannot bind TRAF2 in a lymphoid cell l

207 Finally, we show that MALT1 mutants that alter the Ig3-ubiquitin interface imp

208 oreover, by generating constitutively active MALT1 mutants that overcome the need for monoubiquitinat

209 ption of Malt1 protease function in mice and MALT1 mutations in humans results in reduced regulatory

210 te the therapeutic efficacy of targeting the MALT1-MYC axis in MCL patients.

211 0 CARD is essential for interaction with the MALT1 N terminus.

212 parisons of the bioactivity of intact c-IAP2/MALT1 oncoprotein and BIR1 E47A/R48A c-IAP2/MALT1 mutant

213 lead to the upregulation of either BCL10 or MALT1 or the generation of a fusion protein, cIAP2-MALT1

214 ent and proteolytic cleavage is dependent on MALT1 paracaspase activity.

215 e 1.75-A resolution crystal structure of the MALT1 paracaspase region, which contains the paracaspase

216 ed lymphoid tissue lymphoma translocation 1 (MALT1) paracaspase, a key component of the Carma1/Bcl10/

217 re propose that the pathology characterizing Malt1(PD/PD) animals arises from an immune imbalance fea

218 Surprisingly, Malt1(PD/PD) animals developed a multiorgan inflammatory

219 We found that MALT1(-/-) and MALT1(PD/PD) mast cells are equally impaired in cytokine

220 whereas degranulation is MALT1-independent, MALT1(PD/PD) mice are protected from vascular edema indu

221 Malt1(PD/PD) mice displayed defects in multiple cell typ

222 Consequently, Malt1(PD/PD) mice were protected in a Th17-dependent exp

223 we generated MALT1 protease-deficient mice (Malt1(PD/PD)) and compared their phenotype with that of

224 protein kinase Ctheta (PKCtheta), Bcl10, and Malt1 play critical roles in TCR signaling to the transc

225 MALT1 plays a central role in immune cell activation by

226 The signaling protein MALT1 plays a key role in promoting NF-kappaB activation

227 The paracaspase MALT1 plays an important role in immune receptor-driven

228 API2-MALT1-positive MALT lymphomas manifest antibiotic resist

229 n TCR signaling through PKCtheta, Bcl10, and Malt1 predominantly impair NF-kappaB activation and down

230 API2-MALT1 promotes cell survival and proliferation via activ

231 MALT1 promotes signaling by acting as a scaffold, recrui

232 API2-MALT1 promotes ubiquitination of RIP1 at lysine (K) 377,

233 10 PLCG1 and 3 of 3 CARD11 variants induced MALT1 protease activity and increased transcription from

234 In vitro, inactivation of MALT1 protease activity caused reduced stimulation-induc

235 antly, we find that PAR1 stimulation induces MALT1 protease activity in both osteosarcoma and breast

236 This suggests a role for MALT1 protease activity in endothelial cells targeted by

237 r a previously unappreciated key function of MALT1 protease activity in immune homeostasis and underl

238 ient to drive the cytokine response and that MALT1 protease activity is essential.

239 New data shows that targeting MALT1 protease activity may be a promising therapeutic s

240 ole indicates that therapeutic inhibitors of MALT1 protease could work synergistically to control IgE

241 all, our data revealed a crucial role of the Malt1 protease for the maintenance of intestinal and sys

242 Genetic disruption of Malt1 protease function in mice and MALT1 mutations in h

243 We thus propose a dual role for MALT1 protease in allergic response, mediating 1) IgE-de

244 Several small molecule MALT1 protease inhibitors have recently been described t

245 ed, we find that in human endothelial cells, MALT1 protease is activated following histamine treatmen

246 t cells from MALT1 knockout (MALT1(-/-)) and MALT1 protease-deficient (MALT(PD/PD)) mice to wild-type

247 immune homeostasis and autoimmune disease in Malt1 protease-deficient (Malt1PD) mice and the Ags driv

248 overall immune cell regulation, we generated MALT1 protease-deficient mice (Malt1(PD/PD)) and compare

249 ptosis protein 2) fused with portions of the MALT1 protein.

250 udies have shown that the CARMA1, Bcl10, and MALT1 proteins are critical for coupling the common elem

251 uncover a function of the CARMA, Bcl10, and MALT1 proteins in cells outside the immune system.

252 The CARMA1, Bcl10, and MALT1 proteins together constitute a signaling complex (

253 To investigate how MALT1 proteolytic activity contributes to overall immune

254 n this context, we sought to investigate how MALT1 proteolytic activity contributes to the overall al

255 duced lymphomas with a specific inhibitor of MALT1 proteolytic activity decreased cell viability, ind

256 icient T cells, suggesting a contribution of MALT1 proteolytic activity in T cell activation and EAE

257 nt of CLL cells in vitro with MI-2 inhibited MALT1 proteolytic activity reduced BCR and NF-kappaB sig

258 oid tissue lymphoma translocation protein 1 (MALT1) proteolytic activity in the suppression of autoim

259 heir own growth and survival, and inhibiting MALT1 reduces the viability and growth of these tumors.

260 Because MALT1 remains understudied in this context, we sought to

261 ing FcepsilonRI stimulation, indicating that MALT1 scaffolding activity is insufficient to drive the

262 binds the death domain of MALT1 and inhibits MALT1 scaffolding and proteolytic activities.

263 RNA inhibited NF-kappaB activation by c-IAP2/MALT1 showing that TRAF2 is indispensable.

264 Therefore, we conclude that the Carma1-Bcl10-Malt1 signaling axis is critical for cytokine and chemok

265 signaling activator, MALT1, which disrupted MALT1 signaling complexes.

266 ate that enforced activation of CARD11/BCL10/MALT1 signaling is sufficient to drive transformed B-cel

267 d cell viability, indicating that endogenous Malt1 signaling was required for tumor cell survival.

268 non-immune cells to assemble a CARMA3-Bcl10-MALT1 signalosome and mediate G protein-coupled receptor

269 rotein CARD9, a component of the CARD9-Bcl10-MALT1 signalosome complex involved in NF-kappaB transloc

270 her, we find that although this CARMA3.Bcl10.MALT1 signalosome shares features with a CARMA1-containi

271 caspase, a key component of the Carma1/Bcl10/MALT1 signalosome, is critical for NF-kappaB signaling i

272 requires an intact endothelial CARMA3.Bcl10.MALT1 signalosome, underscoring the importance of the si

273 However, TRAF1/2-binding mutants of c-IAP2.MALT1 still oligomerize and activate NF-kappaB, suggesti

274 o TRAF1 and TRAF2 is not required for c-IAP2.MALT1-stimulated NF-kappaB activation.

275 the importance of TRAF1 and TRAF2 for c-IAP2.MALT1-stimulated NF-kappaB activation.

276 ion of TRAF1 and TRAF2 did not affect c-IAP2.MALT1-stimulated signaling.

277 ubiquitin chain assembly complex as a novel MALT1 substrate.

278 Finally, the MALT1 substrates A20 and CYLD were completely processed

279 To identify new human MALT1 substrates, we compare B cells from the only known

280 cells and irreversibly inhibited cleavage of MALT1 substrates.

281 Furthermore, BCL10 and cIAP2-MALT1 synergistically activate NF-kappaB.

282 Malt1-/- Th cells failed to cleave RelB, a suppressor of

283 n line with their impaired GM-CSF secretion, Malt1-/- Th cells failed to recruit myeloid cells to the

284 reased secretion of Th17 effector cytokines, Malt1-/- Th17 cells showed normal expression of lineage-

285 Mutants of MALT1 that fail to activate caspase-8 and permit c-FLIP(

286 atients of a homozygous missense mutation in MALT1 that resulted in loss of protein expression.

287 BCR signaling, including CARD11, BCL10, and MALT1, that have complex 5'UTRs and encode proteins with

288 RD11), the adaptor BCL10 and the paracaspase MALT1 (the CBM complex), linked to the inhibitor of NF-k

289 In contrast to wild-type human MALT1, the patients' MALT1 mutant failed to correct defe

290 d RIP1 interact with the API2 moiety of API2-MALT1, this moiety alone is insufficient to induce RIP1

291 r 2 (TRAF2) recruitment is required for API2-MALT1 to induce RIP1 ubiquitination, NF-kappaB activatio

292 d demonstrate that RIP1 is required for API2-MALT1 to stimulate canonical nuclear factor kappa B (NF-

293 mphoid tissue lymphoma translocation gene 1 (MALT1) to simultaneously activate the NF-kappaB and c-Ju

294 s followed by assembling of the CARMA1/BCL10/MALT1/TRAF6 complex to SMO.

295 ologic characteristics, such as samples with MALT1 translocations having high expression of MALT1 and

296 One subset, characterized by MALT1 translocations, showed overexpression of nuclear f

297 aB regulators PKC theta, CARMA1, Bcl-10, and MALT1, which connect to the TCR.

298 e T cell receptor (TCR) signaling activator, MALT1, which disrupted MALT1 signaling complexes.

299 gative CARMA3 or silencing CARMA3, Bcl10 and MALT1 with specific siRNAs diminished these LPA-induced

300 nding, suggesting that interaction of c-IAP2/MALT1 with TRAF6 is insufficient for NF-kappaB induction