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 ilitates the association of Carma1 with Bcl0-Malt1.

4 D is associated with homozygous mutations in MALT1.

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

6 and mechanism of paracaspases exemplified by MALT1.

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

8 s activation is dependent on the paracaspase MALT1.

9 ting with the immunoglobulin-like domains of MALT1.

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

11 -kappaB signalling related factors HMGA1 and MALT1.

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

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

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

15 n kinase mediate IKK activation by BCL10 and MALT1.

16 he synthesis of a novel fusion protein, API2-MALT1.

17 ding sequence fusion point for both API2 and MALT1.

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

19 adaptor molecule BCL10, and the paracaspase MALT1.

20 Paracaspase (MALT1), a member of an evolutionarily conserved superfam

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

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

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

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

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

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

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

28 D1 and IgH, BCL2 and IgH, c-myc and IgH, and MALT1 and API2 were detected using probes with a dual-fu

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

30 ization analyses with commercially available MALT1 and IgH break-apart and centromere 3, 7, 12, and 1

31 Expression of recombinant mALT1 and mALT2 proteins in Escherichia coli (E. coli) p

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

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

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

35 The deduced peptides of murine ALT1 (mALT1) and ALT2 (mALT2) share 87% and 93% identity, resp

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

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

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

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

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

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

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

43 he CARD domain protein BCL10 and paracaspase MALT1 are essential for the activation of IkappaB kinase

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

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

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

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

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

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

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

51 Therefore, MALT1, Bcl10, and CARMA1 form a trimolecular complex.

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

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

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

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

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

57 ly, only these oligomeric forms of BCL10 and MALT1 can activate IKK in vitro.

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

59 oligomerization-dependent activation of the MALT1 caspase-like domain.

60 es the oligomerization and activation of the MALT1 caspase-like domain.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

75 MALT1 cleavage activity is linked to the pathogenesis of

76 The paracaspase MALT1 cleaves and removes negative checkpoint proteins,

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

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

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

80 We propose a model whereby both the Bcl10.MALT1 complex and the API2-MALT1 fusion protein activate

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

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

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

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

85 as PDK1-associated CARD11 recruits the Bcl10-MALT1 complex, thereby allowing activation of the IKK co

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

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

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

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

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

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

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

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

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

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

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

97 MALT1-deficient mice show significantly less lung tumor

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

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

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

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

102 Expression of a MALT1 deletion mutant containing only the N-terminal dea

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

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

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

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

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

108 activation of the IKK complex through Bcl10-MALT1-dependent ubiquitination of the IKK complex subuni

109 MALT1 diminishes the activation of apoptotic effector ca

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

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

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

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

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

115 We show here that Bcl10 and MALT1 form a strong and specific complex within the cell

116 Bimp1, Bcl10, and MALT1 form a ternary complex, with Bcl10 bridging the Bi

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

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

119 usly unknown functional diversity among API2/MALT1 fusion products and their function in NF-kappaB si

120 e reprogramming, expression of distinct API2/MALT1 fusion products inhibits DNA damage-induced, p53-m

121 by both the Bcl10.MALT1 complex and the API2-MALT1 fusion protein activate a common downstream signal

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

123 Furthermore, the API2-MALT1 fusion protein also strongly activates NF-kappaB a

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

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

126 tional evidence for the contribution of API2/MALT1 fusion proteins to transformation of cells in cult

127 nscripts encoding structurally distinct API2/MALT1 fusion proteins.

128 To investigate the incidence of API2-MALT1 fusion transcripts among marginal zone lymphomas a

129 API2-MALT1 fusion transcripts were detected in 12 of 57 extra

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

131 genes localize to separate chromosomes, with mALT1 gene (gpt1) on chromosome 15 and mALT2 gene (gpt2)

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

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

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

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 ed Bcl10 and its binding partners Carma1 and MALT1 in mediating the ability of the BCR to activate NF

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 to caspases, suggesting a possible role for MALT1 in the regulation of apoptosis.

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

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

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

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

158 rnary complex, with Bcl10 bridging the Bimp1/MALT1 interaction.

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

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

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

162 use CD3/CD28 costimulation failed to recruit MALT1 into lipid rafts in CARMA1-deficient T cells.

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 Together, these results indicate that MALT1 is a crucial signaling component in the TCR signal

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

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

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

169 This recruitment of MALT1 is dependent on CARMA1 because CD3/CD28 costimulat

170 Recently, it has been shown that MALT1 is involved in mediating TCR signal transduction,

171 In this study, we show that MALT1 is recruited into the lipid rafts of the immunolog

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

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

180 MALT1-knockout mice did not develop any clinical symptom

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

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

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

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

185 )(q21;q21), fuses the IAP-2 gene to the MLT1/MALT1 locus, which encodes the human paracaspase.

186 MALT1 mainly functions as a scaffold protein by recruiti

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

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

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

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

191 MALT1 mediates Ag-induced signaling to the transcription

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

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

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

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

196 e (IKK) to associate with the upstream Bcl10-MALT1 (mucosa-associated lymphatic tissue) adapter compl

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

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

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

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

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

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

203 0 CARD is essential for interaction with the MALT1 N terminus.

204 In addition, we also found that MALT1 not only binds to Bcl10 directly, but also associa

205 The MALT1 oligomers bind to TRAF6, induce TRAF6 oligomerizat

206 ene on chromosome 11 and a novel gene termed MALT1 on chromosome 18.

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

208 ix of 12 patients, with no rearrangements of MALT1 or IgH and no trisomies of 7, 12, or 18 detected.

209 Trisomy 3, but not MALT1 or IgH translocation, is a common genetic abnormal

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

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

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

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

214 MALT1/paracaspase is a caspase-like protein that contain

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

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

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

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

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

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

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

222 API2-MALT1-positive MALT lymphomas manifest antibiotic resist

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

224 Bcl10 and MALT1, products of distinct chromosomal translocations i

225 API2-MALT1 promotes cell survival and proliferation via activ

226 MALT1 promotes signaling by acting as a scaffold, recrui

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

228 10 PLCG1 and 3 of 3 CARD11 variants induced MALT1 protease activity and increased transcription from

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

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

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

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

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

234 demonstrate that different forms of the API2/MALT1 proteins activate both unique and overlapping gene

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

236 We find that a small fraction of BCL10 and MALT1 proteins form high molecular weight oligomers.

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

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

239 To investigate how MALT1 proteolytic activity contributes to overall immune

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

256 ubiquitin chain assembly complex as a novel MALT1 substrate.

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

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

259 cells and irreversibly inhibited cleavage of MALT1 substrates.

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

261 RNAi-mediated silencing of MALT1, TAK1, TRAF6, and TRAF2 suppressed TCR-dependent I

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

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

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

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

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

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

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

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

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

271 ion and protein kinase C activation to Bcl10/MALT1, thus leading to NF-kappaB induction.

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

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

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

275 ctivation in vitro with purified proteins of MALT1, TRAF6, TAK1, and ubiquitination enzymes including

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

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

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

279 itously expressed gene, which we refer to as MALT1, was identified within this sequence and was found

280 B kinase (IKK) complex via Carma1, Bcl10 and MALT1, whereas BAFF-R engagement promotes processing of

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

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

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