ライフサイエンスコーパス: CREM

1 CREM isoforms functioned as efficient transcriptional ac

2 CREM mRNA is robustly expressed in human myocardium, and

3 CREM protein is increased in T cells of patients with sy

4 CREM, in turn, binds protein 300 and cAMP response eleme

5 CREM-IbDeltaC-X transgenic (CREM) mice developed age-dep

6 pitation experiments demonstrate that CREB-1/CREM-1 are recruited to the PE-1/METS promoter as well a

7 r, these findings reveal new roles of CREB-1/CREM-1 as regulators of macrophage differentiation.

8 mplex, which are thought to be CREM tau 1/2, CREM alpha/beta, and S-CREM.

9 s, P<0.05) and relaxation shortening (5+/-5% CREM-/- vs. -18+/-3% controls; P<0.05) at faster rates.

10 with less contractile augmentation (+22+/-9% CREM-/- vs.+62+/-11% controls, P<0.05) and relaxation sh

11 ependent human populations illustrate that a CREM promoter variant at rs12765063 is associated with i

12 ur data suggest that upon T cell activation, CREM gradually replaces phosphorylated CREB at the -180

13 f the cAMP response element modulator alpha (CREM-alpha) and reduced activation of the AKT/mTOR pathw

14 pressor (ICER) I, ICER Igamma, CREM-17X, and CREM-17) from rat pancreatic islets and the RINm5F pancr

15 decrease in repressor-type factors ATF-2 and CREM-1.

16 ession, MIWI complexes with mRNAs of ACT and CREM target genes.

17 r CREB protein family members, i.e. ATF1 and CREM.

18 5, NF-Y to CCAAT boxes, and CREB, ATF1, and CREM to CRE.

19 1 gene homologous to both mammalian CREB and CREM and have characterized in the sensory neurons that

20 hree transcription factors (ATF1, CREB1, and CREM) together led to a significant reduction in the vas

21 on of transcription factors ATF3, FOSL2, and CREM.

22 Whereas MIWI and CREM do not regulate each other's expression, MIWI compl

23 NAs of ACT (activator of CREM in testis) and CREM target genes are downregulated in miwi(null) testes

24 Anti-CREM antibody supershifts this complex.

25 ein complex that was supershifted by an anti-CREM antibody.

26 Antisense CREM also enhanced the accessibility of the IL-2 promote

27 Transfection of an antisense CREM plasmid into T cells blocked the expression and bin

28 ion of CREM mRNA and protein by an antisense CREM plasmid, which was force expressed in SLE T cells b

29 e translation of CREM mRNA with an antisense CREM vector increases the expression of c-fos and the AP

30 Overexpression of either antisense CREM or CREB plasmid rescued morphine-induced inhibition

31 n immunoprecipitation experiments, antisense CREM prevented the binding of protein 300 and cAMP respo

32 Some of the induced genes, such as CREM, CHOP, and MAP kinase phosphatase-1, may be compone

33 ns bind to the 3' enhancer (PU.1, PIP, ATF1, CREM, c-Fos, c-Jun, and E2A), but the mechanism of 3'-en

34 d T cell adenylyl cyclase activity augmented CREM activity and curbed T cell activation and effector

35 CREM gene that accounts for increased basal CREM expression in SLE T cells and reflects disease acti

36 Although the basal CREM levels are increased in T cells from SLE patients c

37 T cells fail to further increase their basal CREM levels upon T cell activation due to a decreased co

38 gel-shifted complex, which are thought to be CREM tau 1/2, CREM alpha/beta, and S-CREM.

39 Because CREM trans-represses c-fos transcription in SLE T cells,

40 an autoregulatory feedback mechanism between CREM and AP-1.

41 d cAMP response element binding protein, but CREM is unable to activate its histone acetyltransferase

42 est which core clock genes are controlled by CREM/ICER in the liver and adrenal gland.

43 ivation of the insulin gene transcription by CREM activator is mediated by not only direct binding to

44 Because KIF17b has been reported to control CREM-dependent transcription in male germ cells by regul

45 This method uses a modified form of Cre (CREM) that contains alterations to the 5' region includi

46 mily of transcription factors, such as CREB, CREM, ATF-1, ATF-2 as well as c-Jun and TTF-1.

47 and antisera to transcription factors CREB, CREM, Fos, and Jun indicate that these proteins, or clos

48 CRE cross-reacted with antibodies for CREB, CREM, ATF1, ATF2, and c-Jun, while proteins binding the

49 AC(VI) did not alter the expression of CREB, CREM, ATF1, ATF2, or ATF4 proteins.

50 is not known which of the isoforms of CREB, CREM, or ATF1 are expressed in the neurons that undergo

51 of the IL-2 promoter is the target of a CREB/CREM transcriptional inhibitor that contributes to the r

52 ue Glu(312), which are conserved in all CREB/CREM/ATF-1 family members.

53 regulated by the transcription factors CREB/CREM (cAMP response element-binding protein/modulator) i

54 demonstrated that transcription factors CREB/CREM and USF1/USF2 in As4.1 cell nuclear extracts bind t

55 rotein/cAMP response element modulator (CREB/CREM), activating transcription factor-2/c-Jun, and Jun-

56 le of dCREB2, the Drosophila homolog of CREB/CREM, in circadian rhythms.

57 specifically reduced the binding of the CREB/CREM complex displayed a decreased ability to be affecte

58 d to an increase in binding of only the CREB/CREM complex.

59 Members of the CREB/CREM/ATF family of transcription factors either enhance

60 that are conserved among members of the CREB/CREM/ATF-1 family of transcription factors.

61 ls by electroporation, resulted in decreased CREM protein binding to the IL-2 promoter and increased

62 E and the time relationship between elevated CREM and reduced Pol II recruitment by the CRH promoter

63 -specific CXCR6(+) CD8 T cells with enhanced CREM expression and transcriptional activity were detect

64 phorylation of CREB-1 and the related factor CREM-1 are stimulated by M-CSF in a SAPK2/p38-dependent

65 GFR signaling or by the transcription factor CREM to promote the Par3 relocation to microtubules, fac

66 a null mutation in the transcription factor CREM.

67 e and the corresponding transcription factor CREM.

68 Based on the requirement for CREM/ICER and Rad6B proteins in spermatogenesis, we dete

69 Our results provide support for CREM as a therapeutic target to enhance the antitumour e

70 Functionally, CREM deletion enhances CAR-NK cell effector function bot

71 Furthermore, CREM activator interacted directly with the transcriptio

72 of GnRH-CREB KO mice with and without global CREM deletion revealed normal puberty onset.

73 ed that GnRH-CREB KO with and without global CREM deletion were normal up to approximately 9 months o

74 se element modulator (CREM) deletion (global-CREM KOs) to investigate the role of CREB in estrogen ne

75 levels were abnormal in GnRH-CREB KO/global-CREM KO mice.

76 n autoimmune and inflammatory diseases, ICER/CREM-deficient B6.lpr mice are protected from developing

77 tal encephalomyelitis are attenuated in ICER/CREM-deficient mice compared with their ICER/CREM-suffic

78 In vitro differentiation from naive ICER/CREM-deficient CD4(+) T cells to Th17 cells is impaired

79 ction via the transcriptional regulator ICER/CREM and upregulating IL-10 after interaction of the CD4

80 CREM-deficient mice compared with their ICER/CREM-sufficient littermates.

81 Western blot analysis identifies CREM tau protein in the protein-DNA complex formed betwe

82 ntial of cathelicidin and further identifies CREM as a repressor of cathelicidin in Leishmania infect

83 These findings implicate the IFNbeta/CREM/IL-2 axis in regulating T-lymphocyte function durin

84 c AMP early repressor (ICER) I, ICER Igamma, CREM-17X, and CREM-17) from rat pancreatic islets and th

85 More importantly, CREM promoter activity mirrors reliably disease activity

86 out increased protein levels (all P<0.01) in CREM-/- vs. controls.

87 opment of a substrate for long-lasting AF in CREM mice.

88 o atrial remodeling and development of AF in CREM-TG mice.

89 ogy, and myocardial histology were normal in CREM-null animals.

90 se II-mediated RyR2-S2814 phosphorylation in CREM mice normalized open probability of RyR2 channels a

91 A) is able to attenuate atrial remodeling in CREM-IbDeltaC-X (cAMP responsive element modulator isofo

92 The development of sAF in CREM mice was preceded by enhanced diastolic Ca(2+) rele

93 es the development of a substrate for sAF in CREM mice, the first demonstration of a molecular mechan

94 anced transcriptional activity and increased CREM expression.

95 s from healthy individuals display increased CREM expression after T cell activation, most likely thr

96 lls exposed to AML blasts revealed increased CREM expression and transcriptional activity, indicating

97 Here, we show that increased CREM expression is the result of enhanced promoter activ

98 -regulation is responsible for the increased CREM protein levels and that CREM binds to the IL-2 prom

99 and interleukin-15 signalling rapidly induce CREM upregulation in NK cells.

100 yocyte-directed expression of the inhibitory CREM isoform CREM-IbDeltaC-X in transgenic mice (TG) lea

101 Knocking out the inhibitory CREM/ICER isoform in T cells, however, failed to rescue

102 Here, we identify a novel intronic CREM promoter (denoted P2) in front of the second exon o

103 ed expression of the inhibitory CREM isoform CREM-IbDeltaC-X in transgenic mice (TG) leads to spontan

104 chemically resolved electrical measurements (CREM) confirmed the successful encapsulation of M within

105 sis revealed that other CREB family members, CREM and ATF1, are up-regulated and associate with the p

106 transfection models and genetically modified CREM-deficient and CREMalpha-overexpressing T cells, we

107 rm of cAMP response element (CRE) modulator (CREM), inducible cAMP early repressor (ICER), in limitin

108 the cAMP-responsive element (CRE) modulator (CREM).

109 l repressor cAMP response element modulator (CREM) alpha has important roles in normal T cell physiol

110 tion factor cAMP response element modulator (CREM) alpha promotes altered cytokine expression in SLE.

111 on factor cAMP responsive element modulator (CREM) alpha, which is expressed at increased levels in T

112 isoforms of cAMP-response element modulator (CREM) and blocked both trans-activation of CCND2 by vari

113 ssor (ICER)/cAMP response element modulator (CREM) and down-regulation of p-cAMP-response element-bin

114 actor cyclic AMP response element modulator (CREM) as a crucial regulator of NK cell function.

115 hout global cAMP response element modulator (CREM) deletion (global-CREM KOs) to investigate the role

116 tivity of cAMP-responsive element modulator (CREM) distinct from T cell exhaustion.

117 like the cAMP-Responsive Element Modulator (CREM) gene.

118 The cAMP response element modulator (CREM) has been shown to bind specifically to the -180 si

119 al striatal cAMP-response element modulator (CREM) in mediating impulsivity relevant to drug abuse vu

120 The cAMP response element modulator (CREM) is known to form complexes with CREB and bind to t

121 epressor, cAMP-responsive element modulator (CREM) is reduced.

122 The cAMP response element modulator (CREM) plays pivotal roles in the hypothalamic-pituitary-

123 tion factor cAMP-response element modulator (CREM) protein, plays a major role in cAMP-responsive gen

124 h levels of cAMP response element modulator (CREM) that binds to the IL-2 promoter and represses the

125 vels of the cAMP response element modulator (CREM) that has been shown to bind to the IL-2 promoter a

126 ne by cyclic AMP response element modulator (CREM) through four cyclic AMP response elements (CREs).

127 f the cyclic AMP-response element modulator (CREM) to inhibit cyclic AMP-response element binding pro

128 ily protein cAMP response-element modulator (CREM) was observed after CREB deletion.

129 ATF1 and cAMP-responsive element modulator (CREM), may play a role.

130 cAMP response element modulator (CREM), the repressor of VDR, was induced in infection, r

131 A levels of cAMP response element modulator (CREM)-17X and inducible cAMP early repressor were signif

132 specific cAMP-responsive element modulator (CREM)-regulated mRNAs.

133 form of the cAMP response element modulator (CREM).

134 tion factor cAMP response element modulator (CREM)alpha contributes to various cellular and molecular

135 on factor cAMP-responsive element modulator (CREM)alpha displays increased expression levels in T cel

136 ry factor cAMP-responsive element modulator (CREM)alpha in SLE T lymphocytes and subsequent CREMalpha

137 on factor cAMP-responsive element modulator (CREM)alpha was reported to be abnormally increased in T

138 the role of cAMP-response element modulator (CREM)tau in testis ACE transcription.

139 tion of the cAMP response element-modulator (CREM) gene yields activator and repressor isoforms, incl

140 We demonstrate that cAMP response modulator (CREM)alpha contributes to epigenetic remodeling of IL2 i

141 Despite this similarity, most CREM isoforms are transcriptional repressors.

142 in controlling the expression of myometrial CREM splice variants.

143 We isolated two novel CREM isoforms (CREMDeltaQ1 and CREMDeltaQ2), which lack

144 Furthermore, the ability of CREM to bind the CRH CRE and the time relationship betwe

145 In accordance, ablation of CREM expression or inhibition of histone deacetylases ac

146 vealed a 5-fold increase in the abundance of CREM-17X mRNA and a concomitant 50% reduction in the ins

147 Furthermore, mRNAs of ACT (activator of CREM in testis) and CREM target genes are downregulated

148 the transcriptional coactivator activator of CREM in testis, this indicates that one kinesin links th

149 cells blocked the expression and binding of CREM to the IL-2 promoter and the decrease of IL-2 produ

150 y pathways that lead to increased binding of CREM to the IL-2 promoter in SLE T cells.

151 ession of CREM protein, increased binding of CREM to the IL-2 promoter, and decreased IL-2 promoter a

152 motifs present in the alternatively exons of CREM.

153 responsible for the increased expression of CREM and the decreased production of IL-2 in SLE T cells

154 can account for the increased expression of CREM and the suppression of IL-2 production.

155 Suppression of the expression of CREM mRNA and protein by an antisense CREM plasmid, whic

156 LE serum resulted in increased expression of CREM protein, increased binding of CREM to the IL-2 prom

157 ported that this change in the expression of CREM spliced variants is likely to have important ramifi

158 known about the physiological importance of CREM in intact hearts remains unknown.

159 analysis revealed a significant induction of CREM in CAR-NK cells during the peak of effector functio

160 hanistically, we establish that induction of CREM is mediated by the PKA-CREB signalling pathway, whi

161 ese results demonstrate novel involvement of CREM in regulation of PP1 activity and of PLB, likely re

162 l overexpression of the activator isoform of CREM, CREMtau, in the hippocampus also resulted in an ac

163 promoter suggest that inhibitory isoforms of CREM induced during stress contribute to the decline in

164 Thus, levels of CREM in T cells determine the outcome of ALI, and CREMal

165 and to be involved in the overexpression of CREM and its binding to the IL-2 promoter.

166 Overexpression of CREM-17X in intact islets via adenovirus infection decre

167 spermatid stage, resembling the phenotype of CREM, a master regulator of spermiogenesis.

168 ecipitation assays showed the recruitment of CREM by the CRH CRE in conjunction with decreases in RNA

169 Reduction of CREM expression in wild-type CD4 T lymphocytes prevents

170 interacting with the basic/zipper region of CREM, recruits CBP to the viral promoter.

171 remarkable differences in the regulation of CREM expression in response to T cell activation.

172 er, these data suggest that up-regulation of CREM repressors by either FFA or high glucose exacerbate

173 SRp40 regulates the splicing of CREM via its interactions with multiple ESE motifs prese

174 esulting from the transcriptional stimuli of CREM are dictated by the expression of multiple protein

175 Finally, an adoptive transfer of CREM(-/-) CD4(+) T cells, but not of wild-type T cells i

176 Blockade of the translation of CREM mRNA with an antisense CREM vector increases the ex

177 Our findings extend the understanding of CREM gene regulation in the context of T cell activation

178 protein kinase A (PKA) which is upstream of CREM.

179 ription factors PU.1, NF-EM5, E2A, ATF-1, or CREM.

180 ntrast, little induction is seen for ATF1 or CREM.

181 amily transcription factors (ATF1, CREB1, or CREM).

182 c changes when rescuing with ATF1, CREB1, or CREM.

183 This analysis also identified other CREM isoforms in the gel-shifted complex, which are thou

184 In SLE T cells, p-CREM bound to the transcriptional coactivators, CREB bin

185 rylated cAMP-responsive element modulator (p-CREM) that binds the -180 site of the IL-2 promoter.

186 Increased expression of p-CREM correlated with decreased production of IL-2.

187 m stimulated SLE T cells display primarily p-CREM and decreased p-CREB binding.

188 nt studies showing that CREB and its paralog CREM are required for survival of certain cell types pro

189 CREB, CRE modulator protein (CREM), Fos-B, and Jun-D, but not c-Fos, all contributed

190 s, we determined expression of Cdc34, Rad6B, CREM/ICER isoforms, and the Skp1-Cullin-F-box ubiquitin

191 Competitive gel shift shows that recombinant CREM tau protein and testis nuclear proteins have a simi

192 PGE2/cAMP/PKA axis was found to regulate CREM induction during infection and silencing CREM in in

193 t to be CREM tau 1/2, CREM alpha/beta, and S-CREM.

194 REM induction during infection and silencing CREM in infected cells and BALB/c mice led to decreased

195 ein complex transporting a group of specific CREM-regulated mRNAs in mammalian male postmeiotic germ

196 hese results highlight that ventral striatal CREM mediates impulsivity related to substance abuse and

197 We studied CREM-null mice and age-matched control littermates by in

198 regulation of the transcriptional suppressor CREM by IFN-beta and consequent recruitment of histone d

199 r the increased CREM protein levels and that CREM binds to the IL-2 promoter in live SLE T cells.

200 We conclude that CREM represses the expression of c-fos and limits the ac

201 In this study, we demonstrate that CREM binds to the proximal promoter of the c-fos proto-o

202 d transfection studies also demonstrate that CREM tau protein is a transcriptional activator of the t

203 We also found that CREM-Ia and ATF-1, which share significant homology in t

204 These data indicate that CREM tau isoforms play an important role as a positive r

205 This indicates that CREM activity was a consequence, rather than the cause,

206 Finally, our findings reveal that CREM exerts its regulatory functions through epigenetic

207 In this study we show that CREM is transcriptionally induced in T cells following s

208 related to substance abuse and suggest that CREM and its regulated network may be promising therapeu

209 lectric activity regulation, suggesting that CREM transgenic mice are a valuable experimental model f

210 The CREM proteins are highly homologous to CREB, particularl

211 On the other hand, the CREM repressor ICER competitively interrupts the binding

212 yses indicated that a specific member of the CREM family, the inducible cAMP early repressor (ICER),

213 1-dependent promoter located upstream of the CREM gene that accounts for increased basal CREM express

214 noted P2) in front of the second exon of the CREM gene that harbors putative binding sites for TATA-b

215 ative splicing enables the expression of the CREM gene to be "switched" within the human myometrium d

216 ranscription: hICERIIgamma, a product of the CREM gene, and hATF5, a novel ATF homolog.

217 One of the products of the CREM gene, the transcriptional repressor Inducible cAMP

218 n factor specificity protein-1 (SP-1) to the CREM promoter resulting in enhanced transcriptional acti

219 1 protein and a stronger SP-1 binding to the CREM promoter.

220 cAMP signaling through CREM (cAMP-responsive element modulator) and its variant

221 Thus, CREM is involved indirectly in the modulation of transcr

222 nt alterations of the gene program linked to CREM-induced atrial remodeling were identified in the ex

223 CREM-IbDeltaC-X transgenic (CREM) mice developed age-dependent progression from spon

224 lin secretion and the mRNA levels of the two CREM repressors to normal.

225 efore suggest that these factors, along with CREM and SP3, direct stage- and cell type-specific trans

226 of the insulin-secreting beta HC9 cells with CREM-17X suppressed rat insulin promoter activity by nea