ライフサイエンスコーパス: CUGBP1

1 CUGBP1 and CRT compete for binding to p21 mRNA and there

2 CUGBP1 and HuR competed for association with the same oc

3 CUGBP1 immunoprecipitated from livers of LPS-treated mic

4 CUGBP1 increases translation of p21 mRNA, whereas CRT bl

5 CUGBP1 is an important skeletal muscle translational reg

6 CUGBP1 is hyperphosphorylated in DM1 tissues, cells, and

7 CUGBP1 is the first GRE-binding protein to have RNA inte

8 CUGBP1 is upregulated in DM1 due to PKC pathway activati

9 CUGBP1 levels are increased in DM1 myoblasts, heart, and

10 CUGBP1 mRNA levels in processing bodies (P-bodies) incre

11 CUGBP1 overexpression decreased HuR binding to occludin

12 CUGBP1 overexpression in preadipocytes from young animal

13 CUGBP1 specifically recognizes sequences within the TNF

14 RNA-binding proteins CUG-binding protein 1 (CUGBP1) and HuR are highly expressed in epithelial tissu

15 DK4) by the action of CUG-binding protein 1 (CUGBP1) and microRNA-222 (miR-222) in intestinal epithel

16 in CUG triplet repeat RNA-binding protein 1 (CUGBP1) and the translation initiation factor eIF2.

17 The RBP CUG-binding protein 1 (CUGBP1) destabilizes and represses the translation of se

18 -acting factor (ITAF) CUG-binding protein 1 (CUGBP1) from in vitro translation extracts or deletion o

19 195 (miR-195) and RBP CUG-binding protein 1 (CUGBP1) jointly regulate IGF2R expression at the posttra

20 CUG-repeat binding protein 1 (CUGBP1) mediates selective mRNA decay by binding to GU-r

21 CUG-binding protein 1 (CUGBP1) was identified as the major GRE-binding activity

22 RNA-binding protein, CUG-binding protein 1 (CUGBP1), regulates gene expression at the levels of alte

23 , also referred to as CUG-binding protein 1 (CUGBP1), regulates the stability and translation of targ

24 teady-state levels of CUG-binding protein 1 (CUGBP1).

25 nd-like 1 (MBNL1) and CUG-binding protein 1 (CUGBP1).

26 that is bound by the CUG-binding protein 1 (CUGBP1).

27 ding proteins such as CUG-binding protein 1 (CUGBP1).

28 g proteins, including CUG-binding protein 1 (CUGBP1).

29 nd-like 1 (MBNL1) and CUG-binding protein 1 (CUGBP1).

30 and up-regulation of CUG binding protein 1 (CUGBP1).

31 CUG triplet repeat-binding protein-1 (CUGBP1) binds to C/EBPbeta mRNA, increasing C/EBPbeta-LI

32 the splicing factor, CUG-binding-protein-1 (CUGBP1), bound to a consensus sequence close to the Bcl-

33 noanalysis of SGs with stress markers TIA-1, CUGBP1, and ph-eIF2, site-specific mutagenesis, and exam

34 escent staining for CUGBP1 and CUGBP2, the 2 CUGBP1 and ETR-3 like factor (CELF) proteins expressed i

35 while normal differentiated cells accumulate CUGBP1 in the cytoplasm.

36 Failure of DM cells to accumulate CUGBP1 in the cytoplasm leads to a significant reduction

37 The activated CUGBP1 binds to the 5' region of C/EBPbeta mRNA and repl

38 increases the levels of CUGBP1 and activates CUGBP1 by phosphorylation, leading to the formation of t

39 s after partial hepatectomy, liver activates CUGBP1 by a hyperphosphorylation.

40 ression of short repeats form foci and alter CUGBP1 and ZNF9; however, long CUG/CCUG repeats misregul

41 with Igf2r mRNA and suggest that miR-195 and CUGBP1 dampen IGF signaling by inhibiting IGF2R translat

42 Both miR-195 and CUGBP1 interacted with the 3' untranslated region (3'-UT

43 Importantly, the miR-195- and CUGBP1-repressed levels of cellular IGF2R led to a disru

44 sion of RNA-binding proteins hnRNP A2/B1 and CUGBP1 suppresses the phenotype of the CGG transgenic fl

45 ion and proteasomal degradation of ezrin and CUGBP1 require Uba6, but not Uba1, and that Uba6 is invo

46 MBNL1 and CUGBP1 are RNA binding proteins that regulate alternativ

47 o be involved in DM1 pathogenesis, MBNL1 and CUGBP1, modify the (iCUG)480 degenerative phenotypes.

48 tors previously implicated in DM1, MBNL1 and CUGBP1, participated in the regulation of E29 splicing.

49 other RNA-binding proteins beyond MBNL1 and CUGBP1, such as Staufen 1 and DDX5, are being identified

50 of CUG and CCUG repeats normalizes ZNF9 and CUGBP1 levels.

51 We used an anti-CUGBP1 antibody to immunoprecipitate CUGBP1 from HeLa cy

52 We found that the age-associated CUGBP1-eIF2 complex binds to the 5' region of HDAC1 mRNA

53 Both CUGBP1 and miR-222 were found to bind the CDK4 mRNA codi

54 Our data demonstrate that both CUGBP1 and CRT interact with GCU repeats within myotonin

55 ominant negative isoform, LIP, is induced by CUGBP1.

56 creased production of LIP can be mediated by CUGBP1 (CUG-repeat RNA-binding protein 1).

57 isregulation of splicing events regulated by CUGBP1 but not those regulated by MBNL1, suggesting dist

58 RF4L1), translation of which is regulated by CUGBP1.

59 Repression of occludin translation by CUGBP1 was due to the colocalization of CUGBP1 and tagge

60 d mRNA decay by recruiting the protein CELF1/CUGBP1.

61 l alternative splicing factors RBFOX2, CELF1/CUGBP1, and MBNL1.

62 RNA binding proteins of the conserved CUGBP1, Elav-like factor (CELF) family contribute to hea

63 The complex contains CUGBP1, subunits alpha, beta, and gamma of the initiatio

64 of cellular polyamines increased cytoplasmic CUGBP1 abundance and miR-222 levels, induced their assoc

65 Decreasing CUGBP1 in preadipocytes from old rats by RNA interferenc

66 ing RNA and Dox-regulated shRNA, demonstrate CUGBP1 is inhibitory in vivo.

67 and triggers degradation of dephosphorylated CUGBP1 (de-ph-S302-CUGBP1) or S302A mutant CUGBP1.

68 Reporter assays coupled with knocking down CUGBP1 levels by small interfering RNA and Dox-regulated

69 using an antisense RNA (antagomir) enhanced CUGBP1 biosynthesis and elevated its abundance; neither

70 Ectopically expressed CUGBP1 and miR-195 repressed IGF2R translation cooperati

71 ating the expression of the splicing factors CUGBP1, hnRNPH, hnRNPA1, hnRNPA2B1, and SF2/ASF.

72 In senescent fibroblasts, CUGBP1 displaces CRT from the p21 mRNA and releases CRT-

73 ducing the embryonic expression patterns for CUGBP1 and MBNL1 in adult heart induces the embryonic sp

74 Activation of PKC is required for CUGBP1 hyperphosphorylation in DM1 cells, and PKCalpha a

75 These results strongly support a role for CUGBP1 up-regulation in DM1 pathogenesis.

76 PK-CUG RNA expression, suggesting a role for CUGBP1-specific splicing or cytoplasmic functions in mus

77 Two binding sites for CUGBP1 are located side by side between the first and se

78 idization and immunofluorescent staining for CUGBP1 and CUGBP2, the 2 CUGBP1 and ETR-3 like factor (C

79 We generated CUGBP1-S302A knock-in mice and found that the reduction

80 ion is achieved instead through the hnRNP H2/CUGBP1-mediated interaction of the 5'- and 3'-UTRs of th

81 ans-activator transgenes, we expressed human CUGBP1 in adult mouse heart.

82 The hyperphosphorylated CUGBP1 also interacts with the alpha and beta subunits o

83 an anti-CUGBP1 antibody to immunoprecipitate CUGBP1 from HeLa cytoplasmic extracts and analyzed the a

84 levation of the HDAC1-C/EBPbeta complexes in CUGBP1 transgenic mice reduces expression of C/EBPalpha

85 thway in liver proliferation was examined in CUGBP1 transgenic mice, which display high levels of the

86 which has been shown previously to result in CUGBP1 phosphorylation, also causes TNF mRNA stabilizati

87 n of several RNA-binding proteins, including CUGBP1.

88 elevated in fat tissue with aging, increased CUGBP1 protein, CUGBP1 binding activity, and C/EBPbeta-L

89 ization of MBNL1 with RNA foci and increased CUGBP1 occurred within hours of induced expression of CU

90 ic histological abnormalities, and increased CUGBP1 protein levels.

91 ever, the molecular mechanisms for increased CUGBP1 in DM1 are unclear.

92 Our results indicate that increased CUGBP1 protein levels are associated with DMPK-CUG RNA e

93 is study, we show that aging liver increases CUGBP1 translational activities by induction of a high m

94 general protective effect on PKC-independent CUGBP1 increase.

95 Using tetracycline-inducible CUGBP1 and heart-specific reverse tetracycline trans-act

96 nction, whereas HuR overexpression inhibited CUGBP1 association with occludin mRNA and promoted occlu

97 ; however, long CUG/CCUG repeats misregulate CUGBP1 and ZNF9 much faster than high levels of the shor

98 t with reduction of CUGBP1 in animal models, CUGBP1 is reduced in patients with pediatric liver cance

99 ntaining 960 CUG repeats in skeletal muscle, CUGBP1 up-regulation is temporally correlated with sever

100 d CUGBP1 (de-ph-S302-CUGBP1) or S302A mutant CUGBP1.

101 is associated with elimination of the mutant CUGBP1.

102 Moreover, alterations in nuclear CUGBP1 preceded Bcl-x splicing changes.

103 orylation of CUGBP1 and decreased ability of CUGBP1 to bind to GRE-containing RNA.

104 The ability of CUGBP1 to induce LIP translation during APR depends on p

105 t the reduction of translational activity of CUGBP1 causes development of a fatty liver phenotype in

106 suggest that alterations in the activity of CUGBP1 causes disruption of p21-dependent control of cel

107 Abundance and nucleotide binding activity of CUGBP1 increased with aging in preadipocytes.

108 The translational activity of CUGBP1 is activated by dephosphorylation at Ser302.

109 The binding activity of CUGBP1 to the 5' region of C/EBPbeta mRNA shows increase

110 IFNbeta signaling regulates the activity of CUGBP1, resulting in increased expression of LIP and sup

111 ated with alterations in binding activity of CUGBP1.

112 Addition of CUGBP1 into a cell-free translation system leads to incr

113 ltured cells results in the re-allocation of CUGBP1 from a free state to the RNA.protein complexes co

114 Alteration of CUGBP1 in DM is accompanied by alteration in translation

115 '-UTR) of Igf2r mRNA, and the association of CUGBP1 with Igf2r mRNA enhanced miR-195 binding to Igf2r

116 th the eIF2alpha enhances the association of CUGBP1 with ribosomes and correlates with increased tran

117 n by CUGBP1 was due to the colocalization of CUGBP1 and tagged occludin RNA in processing bodies (P-b

118 molecular weight protein-protein complex of CUGBP1.

119 MBNL1 knockout mice, but the consequence of CUGBP1 overexpression in adult muscle is not known.

120 isruption of CUG/CCUG foci and correction of CUGBP1 and ZNF9.

121 To test the role of Gank in degradation of CUGBP1, we generated mice with liver-specific deletion o

122 Small interference RNA-mediated depletion of CUGBP1 decreased IRES activity from bicistronic template

123 Depletion of CUGBP1 from mouse myoblasts results in increased abundan

124 location to P-bodies via the displacement of CUGBP1.

125 Elevation of CUGBP1 and reduction of ZNF9 were also observed before s

126 e have examined the role of the elevation of CUGBP1 and the role of cyclin D3-cdk4-mediated phosphory

127 uring APR is accompanied by the elevation of CUGBP1 binding activity on polysomes.

128 Our data demonstrate that the elevation of CUGBP1 in skeletal muscle causes overexpression of MEF2A

129 by miR-503 in turn altered the expression of CUGBP1 target mRNAs and thus increased the sensitivity o

130 e and skeletal muscle-specific expression of CUGBP1.

131 osphorylation of CUGBP1 and the formation of CUGBP1-C/EBPbeta mRNA complexes in the human monocytic U

132 aggregation with a simultaneous increase of CUGBP1 and a reduction of ZNF9.

133 Induction of CUGBP1 binding activity in liver cytoplasm during APR is

134 Our data demonstrate that the interaction of CUGBP1 with the eIF2alpha enhances the association of CU

135 these mice, the tumor suppressor isoform of CUGBP1 is protected from Gank-mediated degradation.

136 siRNA-mediated knockdown of CUGBP1 in HeLa cells caused stabilization of GRE-contain

137 t diethylnitrosamine increases the levels of CUGBP1 and activates CUGBP1 by phosphorylation, leading

138 ies showed that both the increased levels of CUGBP1 and cdk4-mediated hyper-phosphorylation of CUGBP1

139 ated with the elevation of protein levels of CUGBP1 and with the hyper-phosphorylation of CUGBP1 by a

140 lexes is associated with increased levels of CUGBP1 protein and its binding activity.

141 oforms in DM patients with altered levels of CUGBP1 showed that translation of a dominant negative is

142 In contrast, increasing the levels of CUGBP1 worsens (iCUG)480-induced degeneration even thoug

143 ylation and decreased steady-state levels of CUGBP1.

144 cle of DM1 patients with increased levels of CUGBP1.

145 otein synthesis showed that the half-life of CUGBP1 is increased in cells expressing CUG repeats.

146 of HDAC1 in cultured cells, in the livers of CUGBP1 transgenic mice, and in the livers of mice inject

147 RNA, whereas in DM patients the majority of CUGBP1 is associated with RNA containing CUG repeats.

148 ed that, in control tissues, the majority of CUGBP1 is free of RNA, whereas in DM patients the majori

149 The number of CUGBP1 target transcripts decreased dramatically followi

150 er, we examine the role of overexpression of CUGBP1 in DM1 muscle pathology using transgenic mice tha

151 A large percentage of CUGBP1 target transcripts exhibited rapid and transient

152 t of activation-dependent phosphorylation of CUGBP1 and decreased ability of CUGBP1 to bind to GRE-co

153 that IFNbeta induces the phosphorylation of CUGBP1 and the formation of CUGBP1-C/EBPbeta mRNA comple

154 1 and cdk4-mediated hyper-phosphorylation of CUGBP1 are involved in the age-associated induction of t

155 CUGBP1 and with the hyper-phosphorylation of CUGBP1 by a cyclin D3-cdk4 kinase, activity of which is

156 f cyclin D3-cdk4-mediated phosphorylation of CUGBP1 in the formation of the CUGBP1-eIF2 complex by us

157 ion during APR depends on phosphorylation of CUGBP1.

158 ough activation-dependent phosphorylation of CUGBP1.

159 Consistent with reduction of CUGBP1 in animal models, CUGBP1 is reduced in patients w

160 and that the Gank-UPS-mediated reduction of CUGBP1 is a key event in the development of liver cancer

161 ur results demonstrate that up-regulation of CUGBP1 is sufficient to reproduce molecular, histopathol

162 dentify miR-503 as both a novel regulator of CUGBP1 expression and a modulator of intestinal epitheli

163 Repression of CUGBP1 by miR-503 in turn altered the expression of CUGB

164 Sm4 decreased miR-503-mediated repression of CUGBP1 expression.

165 in hyperphosphorylation and stabilization of CUGBP1.

166 ues, we examined the intracellular status of CUGBP1 in DM patients as well as in cultured cells over

167 re-miR-503) reduced the de novo synthesis of CUGBP1 protein, whereas inhibiting miR-503 by using an a

168 been previously described to be a target of CUGBP1.

169 We identified 613 putative mRNA targets of CUGBP1 and found that the UGUUUGUUUGU GRE sequence and a

170 to identify the cytoplasmic mRNA targets of CUGBP1 in resting and activated primary human T cells an

171 d the levels of the translational targets of CUGBP1 were shown to be elevated in DM2 myoblasts.

172 lex, which is an activator of translation of CUGBP1-dependent mRNAs.

173 CUG repeat-dependent translocation of CUGBP1 into RNA-protein complexes is associated with inc

174 ology using transgenic mice that overexpress CUGBP1 in skeletal muscle.

175 the skeletal muscle from mice overexpressing CUGBP1 is characterized by a developmental delay, muscul

176 Adult mouse skeletal muscle overexpressing CUGBP1 reproduces molecular and physiological defects of

177 In cells from normal patients, CUGBP1 up-regulates p21 protein during differentiation.

178 d PKCalpha and betaII directly phosphorylate CUGBP1 in vitro.

179 With aging, preadipocyte CUGBP1 abundance and activity increases, resulting in en

180 duced endogenous miR-503 levels and promoted CUGBP1 expression, an effect that was prevented by ectop

181 ession of the CUG-repeat RNA-binding protein CUGBP1 and the integrity of the CUG-rich intercistronic

182 quence through which the RNA-binding protein CUGBP1 elicits mRNA decay.

183 The RNA binding protein CUGBP1 is a key regulator of translation of CCAAT enhanc

184 The RNA-binding protein CUGBP1 regulates translation of proteins in a variety of

185 wn to interact with the mRNA-binding protein CUGBP1, a protein known to interact with the alpha and b

186 liver is mediated by the RNA-binding protein CUGBP1.

187 previously characterized RNA-binding protein CUGBP1.

188 nt evidence that CUG repeat binding protein, CUGBP1, interacts with the 5' region of C/EBPbeta mRNA a

189 CUG triplet repeat binding protein, CUGBP1, plays a critical role in the development of skel

190 An RNA CUG triplet repeat binding protein, CUGBP1, regulates splicing and translation of various RN

191 reviously identified an RNA binding protein, CUGBP1, which binds to GCN repeats located within the 5'

192 s to the induction of a CUG-binding protein, CUGBP1, which increases translation of several proteins

193 plasmic levels of a CUG RNA binding protein, CUGBP1, while normal differentiated cells accumulate CUG

194 ressor activities of an RNA binding protein, CUGBP1.

195 tissue with aging, increased CUGBP1 protein, CUGBP1 binding activity, and C/EBPbeta-LIP in preadipocy

196 Two RNA-binding proteins, CUGBP1 and calreticulin (CRT), interact with the same nu

197 Two RNA-binding proteins, CUGBP1 and calreticulin, have been implicated in the tra

198 istent with these observations, the purified CUGBP1-eIF2 complex binds to the 5' region of C/EBPbeta

199 r findings indicate that polyamine-regulated CUGBP1 and miR-222 modulate CDK4 translation at least in

200 Many of the transiently up-regulated CUGBP1 target transcripts encode important regulatory pr

201 RNAs, but the exact mechanism that regulates CUGBP1 abundance remains elusive.

202 th three sites of the CUGBP1 mRNA, represses CUGBP1 expression.

203 this work presents evidence that de-ph-S302-CUGBP1 is a tumor suppressor protein and that the Gank-U

204 ation of dephosphorylated CUGBP1 (de-ph-S302-CUGBP1) or S302A mutant CUGBP1.

205 is colocalization was abolished by silencing CUGBP1 and miR-222.

206 coding region sites than through the single CUGBP1 3'-untranslated region target site.

207 ality in transgenic mice with heart-specific CUGBP1 upregulation, indicating that PKC inhibition did

208 due to PKC pathway activation and subsequent CUGBP1 protein hyperphosphorylation and stabilization.

209 Finally, we demonstrate that CUGBP1 is not only required for IFNbeta-mediated inducti

210 Our data demonstrate that CUGBP1 protein is an important component for the regulat

211 Here we present evidence that CUGBP1 and HuR jointly regulate the translation of occlu

212 tivated primary human T cells and found that CUGBP1 targets were highly enriched for the presence of

213 Our data support the hypothesis that CUGBP1 increases translation of LIP by the interaction w

214 Here we directly test the hypothesis that CUGBP1 up-regulation also contributes to manifestations

215 These findings indicate that CUGBP1 represses occludin translation by increasing occl

216 These results indicate that CUGBP1 upregulation is an early and primary response to

217 Overall, our results show that CUGBP1 binding to certain GRE-containing target transcri

218 Several lines of evidence show that CUGBP1 induces the translation of p21 via binding to a G

219 Further analyses showed that CUGBP1 also increases expression of HDAC1 in cultured ce

220 We showed that CUGBP1 bound specifically to the GU-repeat sequence and

221 proteins from rat liver after PH showed that CUGBP1 is associated with polysomes that translate low m

222 y which CUGBP1 up-regulates MEF2A shows that CUGBP1 increases translation of MEF2A via direct interac

223 Our results suggest that CUGBP1 coordinately regulates the mRNA decay of a networ

224 esults from this study strongly suggest that CUGBP1 has a major role in DM1 skeletal muscle pathogene

225 These results suggest that CUGBP1 is a previously unrecognized downstream effector

226 Our data suggest that CUGBP1-mediated overexpression of MEF2A and p21 inhibits

227 GRE-containing transcripts, suggesting that CUGBP1 is a mediator of GRE-dependent mRNA decay.

228 The CUGBP1-eIF2 complex is bound to C/EBPbeta mRNA in the li

229 The CUGBP1.GRE complex has no activity on its own but specif

230 ical functions of the 20S proteasome and the CUGBP1-eIF2 complexes, the stability of short-lived prot

231 ational repression of the p53 protein by the CUGBP1-eukaryotic initiation factor 2 (eIF2) repressor c

232 itro translation extracts or deletion of the CUGBP1 binding site on the 3'-UTR of the SHMT1 transcrip

233 edicted to associate with three sites of the CUGBP1 mRNA, represses CUGBP1 expression.

234 horylation of CUGBP1 in the formation of the CUGBP1-eIF2 complex by using CUGBP1 transgenic mice and

235 onstrated that age-mediated induction of the CUGBP1-eIF2 complex changes translation of C/EBPbeta in

236 The induction of the CUGBP1-eIF2 complex in old livers is associated with the

237 The elevation of the CUGBP1-eIF2 complex increases translation of C/EBPbeta a

238 lin D3 levels, leads to the reduction of the CUGBP1-eIF2 complex, normalization of HDAC1 levels, and

239 phorylation, leading to the formation of the CUGBP1-eIF2 complex, which is an activator of translatio

240 clin D3, which enhances the formation of the CUGBP1-eIF2 complex.

241 genic mice, which display high levels of the CUGBP1-eIF2 complex.

242 olved in the age-associated induction of the CUGBP1-eIF2 complex.

243 The causal role of the CUGBP1-HDAC1 pathway in liver proliferation was examined

244 interacts with riboCGG repeats and that the CUGBP1 protein interacts with the riboCGG repeats via hn

245 liver proliferation, we have found that the CUGBP1-HDAC1-C/EBPbeta pathway is activated in human tum

246 ter repressive effect of miR-503 through the CUGBP1 coding region sites than through the single CUGBP

247 s (iCUG)480-induced degeneration even though CUGBP1 distribution is not altered by the expression of

248 Thus, CUGBP1 contributes to regulation of adipogenesis in prim

249 A identified several proteins in addition to CUGBP1 that specifically interact with the GC-rich 5' re

250 vate GRE activity in vivo and GRE binding to CUGBP1 in vitro are identified.

251 ediates coordinated mRNA decay by binding to CUGBP1.

252 ative splicing events that are responsive to CUGBP1 and not MBNL, and these events were found to be m

253 bundance; neither intervention changed total CUGBP1 mRNA levels.

254 r cancer in diethylnitrosamine (DEN)-treated CUGBP1-S302A mice showed these mice develop much more se

255 ormation of the CUGBP1-eIF2 complex by using CUGBP1 transgenic mice and young animals expressing high

256 To investigate whether CUGBP1 is directly affected by expansion of CUG repeats

257 Examination of molecular mechanisms by which CUGBP1 up-regulates MEF2A shows that CUGBP1 increases tr

258 '-UTR of the transcript and interacting with CUGBP1.

259 yamines decreased CDK4 mRNA interaction with CUGBP1 and miR-222, in turn inducing CDK4 expression.