ライフサイエンスコーパス: LEF1

1 LEF1 also directly augments expression of the effector f

2 LEF1 and TOPGAL expression ceased during catagen and tel

3 LEF1 competed with TCF4 for binding to NF-kappaB p65.

4 LEF1 inactivation was associated with a younger age at t

5 LEF1 is a cell-type-specific transcription factor and me

6 LEF1 is a nuclear effector of the Wnt/LRP5/beta-catenin

7 LEF1 is highly expressed in androgen-independent prostat

8 LEF1-mediated MMP13 gene expression is repressed by SIRT

9 soderm), lymphoid enhancer-binding factor 1 (LEF1) and mesoderm posterior BHLH transcription factor 1

10 factors lymphoid enhancer binding factor 1 (LEF1) and transcription factor 7 (TCF7) (T cell factor-1

11 L with lymphocyte enhancer-binding factor 1 (LEF1) as a signature gene.

12 scription factor lymphoid enhancer factor 1 (LEF1) in the postselection expansion of iNKT cells throu

13 eta3 stimulates lymphoid-enhancing factor 1 (LEF1) mRNA synthesis in MEE cells.

14 for the lymphoid enhancer-binding factor 1 (LEF1) transcription factor, reducing LEF1 responsiveness

15 protein lymphoid enhancer-binding factor 1 (LEF1) was found adjacent to the proximal Runx2-binding s

16 activated by the lymphoid enhancer factor 1 (LEF1)/beta-catenin complex, a transducer of wnt signalin

17 enin and lymphoid enhancer-binding factor 1 (LEF1)/T cell factor regulates proliferation in stem cell

18 on activation of lymphoid enhancer factor 1 (LEF1)/T-cell factor (TCF) target genes underlie the onco

19 lymphoid-enhancing factor 1/T cell factor 1 (LEF1/TCF1), the ultimate executor of the Wnt pathway, im

20 scription of the lymphoid enhancer factor-1 (LEF1) gene is aberrantly activated in sporadic colon can

21 get gene lymphoid enhancer binding factor-1 (LEF1) in chronic lymphocytic leukemia (CLL).

22 Lymphoid enhancer-binding factor-1 (LEF1) is a key transcription factor of Wnt signaling.

23 paper is the first to show that the Smad2,4/LEF1 complex replaces beta-catenin/LEF1 during activatio

24 ), 11p15.5 (C11orf21, P=2.15x10(-10)), 4q25 (LEF1, P=4.24x10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/C

25 reporter gene is hyperinduced vegetally in a LEF1/TCF3-binding-site-dependent manner.

26 pression conditions the promoter region of a LEF1 target gene is hypoacetylated.

27 d H4 acetylation patterns, derepression of a LEF1.beta-catenin model system, and transcription of HDA

28 lude that the biological outcome of aberrant LEF1 activation in colon cancer is directed by different

29 We recently showed that aberrant LEF1 expression induces acute myeloid leukemia (AML) in

30 p-regulate synthesis of LEF1 and to activate LEF1 transcription during induction of palatal EMT.

31 Moreover, although LEF1 and TCF4 synergize with beta-catenin and plakoglobi

32 ription, including: MYC, vimentin, AXIN2 and LEF1.

33 ptionally active complex of beta-catenin and LEF1.

34 anscriptional activation by beta-catenin and LEF1/TCF, but Fli-I disrupted the synergy of FLAP1 with

35 ey regulatory mechanism for beta-catenin and LEF1/TCF-mediated transcription and thus for Wnt signali

36 anscriptional activation by beta-catenin and LEF1/TCF.

37 hanceosome consisting of Runx1, CBFbeta, and LEF1.

38 expressed in the developing hippocampus, and LEF1-deficient embryos lack dentate gyrus granule cells

39 The WNT/TCF target genes HOXB9 and LEF1 are identified as mediators of chemotactic invasion

40 The expression of LEF1 and LEF1-regulated genes in primary BL suggests that LEF1 is

41 between the DNA-binding domains of Runx2 and LEF1 was identified and found crucial for LEF1-mediated

42 tooth development at the late bud stage and LEF1 is required for a relay of a Wnt signaling to a cas

43 ecific genes, Rorc and Blk, whereas TCF1 and LEF1 countered the SOX proteins and induced genes of alt

44 ranscription factors, SOX4, SOX13, TCF1, and LEF1, and not by conventional TCR signaling.

45 A novel interaction between the VDR and LEF1 (lymphoid enhancer-binding factor-1) that is indepe

46 y abrogated interactions between the VDR and LEF1 but also impaired the ability of the VDR to enhance

47 ates a novel interaction between the VDR and LEF1 that is mediated by the DNA-binding domain of the V

48 that controls proliferation by antagonizing LEF1/beta-catenin-mediated transcription.

49 As LEF1/TCF3 family transcription factors have previously b

50 d the expression of Wnt target genes such as LEF1, cyclin D1, and fibronectin, depressed LRP6 levels,

51 s; and HMG box transcription factors such as LEF1, TCF1, and Sox4.

52 In transcription assays, LEF1 repressed Runx2-induced activation of the mouse ost

53 e main LEF1 promoter activity and attenuates LEF1 mRNA transcription.

54 strate a direct physical interaction between LEF1/beta-catenin complex and the Dkk4 promoter using Ch

55 To further explore the link between LEF1 expression and the Wnt pathway, we studied two resp

56 -ALL and identified monoallelic or biallelic LEF1 microdeletions in 11% (5 of 47) of these primary sa

57 sion has been overridden, beta-catenin binds LEF1 and the beta-catenin-LEF1 complex is competent to a

58 The mutations impaired both LEF1 binding to beta-catenin and transcriptional activat

59 ls compromised transcriptional activation by LEF1/TCF, beta-catenin and the p160 coactivator GRIP1.

60 to beta-catenin, implying that repression by LEF1 is mediated by promoter-targeted HDAC.

61 We show here that repression by LEF1 requires histone deacetylase (HDAC) activity.

62 cells by down-regulating Wnt (beta-catenin, LEF1) and TGF-beta (Smad2/3, collagen type I, alpha-SMA)

63 beta-catenin binds LEF1 and the beta-catenin-LEF1 complex is competent to activate the expression of

64 th stimulate transcription of a beta-catenin-LEF1-dependent reporter gene.

65 e Smad2,4/LEF1 complex replaces beta-catenin/LEF1 during activation of EMT in vivo by TGFbeta3.

66 ns in AER formation through the beta-catenin/LEF1 pathway.

67 leads to the activation of the beta-catenin/LEF1-dependent pathway.

68 l enhanceosome consisting of RUNX1, CBFbeta, LEF1, and Aly.

69 Concordantly, LEF1 expression is significantly upregulated in ERG-high

70 , gel shift, and luciferase assays confirmed LEF1 occupancy and regulation of the AR promoter.

71 otein can interact, in vitro, with consensus LEF1/TCF3-binding sites found within the Xtwn promoter.

72 and found that transcript levels of CTNNB1, LEF1, FZD8, WNT3A, and SFRP4 were negatively correlated

73 Most importantly, our data defined LEF1 as a direct target of ERG and that LEF1 inhibition

74 t regulation and restores the IRES-dependent LEF1 expression.

75 detected in TCF3 (also known as E2A), EBF1, LEF1, IKZF1 (IKAROS) and IKZF3 (AIOLOS).

76 y submucosal glands, indicating that ectopic LEF1 expression alone is insufficient to induce submucos

77 n these cells, the association of endogenous LEF1 and beta-catenin was induced by stimulation with th

78 on assays detected YY1 binding to endogenous LEF1 P2.

79 constitutively active beta-catenin enhanced LEF1-dependent repression of Runx2.

80 nase (MMP) 13, partially because of enhanced LEF1 transcriptional activity.

81 tokine involved in OA pathogenesis, enhanced LEF1 protein levels and gene expression, resulting in in

82 eta-catenin deacetylation, thereby enhancing LEF1-beta-catenin complex formation and long-range chrom

83 In this study, we examined LEF1 expression in androgen-independent cancer as well a

84 antly expressed TCF4 and to a lesser extent, LEF1 and TCF3 mRNA.

85 The HMG-box transcription factor LEF1 controls many developmentally regulated genes, incl

86 rough repression of the transcription factor LEF1, a known modulator of MMP13 gene expression.

87 tion of the proinvasive transcription factor LEF1.

88 yte enhancer binding factor 1/T cell factor (LEF1/TCF) proteins with the assistance of multiple coreg

89 any member of the lymphoid enhancer factor (LEF1) and T-cell factor (TCF1, TCF3, TCF4) family of tra

90 Tc1), and lymphoid enhancer-binding factor1 (LEF1) proteins.

91 Lymphoid-enhancing factor/T-cell factors (LEF1/TCF) are a high-mobility group of transcriptional f

92 n enhanced affinity of S37A beta-catenin for LEF1 and TCF4, as observed here by immunoprecipitation a

93 nd LEF1 was identified and found crucial for LEF1-mediated repression of Runx2.

94 n promoter was surprisingly not required for LEF1 repression.

95 y supports a functionally important role for LEF1 and its target genes in BLs.

96 First, HDAC1 is dissociated from LEF1 and its enzymatic activity is attenuated.

97 Further, LEF1 associates in vivo with HDAC1, and transcription of

98 ded with upregulation of hair-related genes, LEF1 and WNT10B, and downregulation of a marker of sebac

99 ed TCR-translocated oncogene partners: GNAG, LEF1, NKX2-4, and IL2RB.

100 High LEF1 expression (LEF1high) associated with significantly

101 ectal carcinomas, most of which express high LEF1 levels.

102 eloid leukemia (AML) in mice, and found high LEF1 expression in a subset of cytogenetically normal AM

103 In summary, we provide evidence that high LEF1 expression is a novel favorable prognostic marker i

104 ated virus was used to overexpress the human LEF1 gene in a human bronchial xenograft model of regene

105 Thus, we identified LEF1 as a potential marker for androgen-independent dise

106 n of SIRT1 during IL-1beta challenge impeded LEF1 levels and MMP13 gene expression.

107 LNCaP) cells revealed 100-fold increases in LEF1 expression in LNCaP-AI cells.

108 this study, we assessed the role of SIRT1 in LEF1-mediated MMP13 gene expression in human OA chondroc

109 ith survival of patients with MDS, including LEF1, CDH1, WT1, and MN1.

110 artilage from Sirt1(-/-) presented increased LEF1 and MMP13 protein levels, similar to human OA carti

111 ng T cells preferentially express inhibitory LEF1 and TCF7 (TCF-1) isoforms and that T cell activatio

112 e activation of a promoter for a full-length LEF1 isoform that binds beta-catenin, but not a second,

113 es can activate the promoter for full-length LEF1, indicating that in cancer high levels of these com

114 and/or progenitor cell markers ALDH1, LGR5, LEF1, CD133 and CK6B.

115 thelial-mesenchymal phenotype presenting low LEF1 expression, the NAT is synthesized and remains unpr

116 , this unspliced NAT down-regulates the main LEF1 promoter activity and attenuates LEF1 mRNA transcri

117 We show that the TCF family members LEF1, TCF4, and TCF3 are phosphorylated in embryonic ect

118 PBepsilon, RUNX1/AML1, Notch family members, LEF1, and Cdc42 as additional nodes in this pathway.

119 ivo with HDAC1, and transcription of a model LEF1-dependent target gene is modulated by the ratio of

120 ed nuclear export, human TCF4, but not mouse LEF1 or Xenopus TCF3, can repress endoderm genes in MS,

121 e vertebrate TCF proteins (human TCF4, mouse LEF1 and Xenopus TCF3) in C. elegans embryos and compare

122 expressed the highest levels of Lef1 mRNAs, LEF1 concentrated in the precursor cells to the hair sha

123 Mutant LEF1 not only inhibited expression of beta-catenin targe

124 y either overexpression of dominant-negative LEF1 or overexpression of a secreted Wnt inhibitor Dickk

125 ominant-negative Smad4 and dominant-negative LEF1 showing that TGFbeta3 uses Smads both to up-regulat

126 down of LEF1 in BL cell lines identified new LEF1 target genes; these LEF1 targets are enriched with

127 ammatory pathways and were enriched for NF1, LEF1, and other transcription factors.

128 t signaling in prostate cancer and nominates LEF1 as a critical mediator of ERG-induced tumorigenesis

129 helial cells, and neither NAT transcript nor LEF1 mRNA are expressed, in cell lines with an intermedi

130 er B cells were devoid of detectable nuclear LEF1 expression, as were mantle cell lymphoma (0 of 5),

131 Herein, we report the expression of nucleic LEF1 in 15 of 18 patients with BL and the identification

132 -Smad2 and Smad4 are present in the nucleus, LEF1 is activated without beta-catenin.

133 l are uniquely potent in their activation of LEF1 and CDX1.

134 her, these findings imply that activation of LEF1-dependent genes by beta-catenin involves a two-step

135 Aberrant activations of LEF1/TCF-mediated transcription have been implicated in

136 c1 and decreases transcriptional activity of LEF1 proteins.

137 rbored nonsynonymous sequence alterations of LEF1, 2 of which produced premature stop codons.

138 hese data establish the mechanistic basis of LEF1 splicing regulation and demonstrate that LEF1 alter

139 of antisense transcription in the control of LEF1 transcription factor expression.

140 t phosphorylation caused the dissociation of LEF1, TCF4, and TCF3 from a target promoter in vivo.

141 the epidermal and mesenchymal expression of LEF1 and (&bgr;)-catenin, suggesting that these changes

142 The expression of LEF1 and LEF1-regulated genes in primary BL suggests tha

143 everal cell lines revealed the expression of LEF1 mRNA and a constitutive association of the LEF-1 pr

144 Expression of the spliced form of LEF1 NAT in trans prevents the action of unspliced NAT b

145 8 patients with BL and the identification of LEF1 target genes.

146 Here we demonstrate that inclusion of LEF1 exon 6 is increased during thymic development and i

147 ressed, resulting from variable inclusion of LEF1 exon 6; however, the expression pattern of these is

148 om a promoter present in the first intron of LEF1 gene and undergoes splicing in mesenchymal cells.

149 At least two distinct isoforms of LEF1 are expressed, resulting from variable inclusion of

150 ssion profiling after transient knockdown of LEF1 in BL cell lines identified new LEF1 target genes;

151 Knockdown of LEF1, a downstream target of Wnt signaling, abrogated Ha

152 , however, what is the cellular mechanism of LEF1 signaling in regulating tooth morphogenesis.

153 tor in vitro leads to the down-regulation of LEF1 and TCF7 (TCF-1) expression in human naive CD8 T ce

154 We validated the prognostic relevance of LEF1 expression by quantitative PCR, thereby providing a

155 ized to functionally investigate the role of LEF1 in initiating and supporting gland development in t

156 tivation occurred transiently in a subset of LEF1-positive cells of pluripotent ectoderm and underlyi

157 uses Smads both to up-regulate synthesis of LEF1 and to activate LEF1 transcription during induction

158 in a manner mimicking the C-terminal tail of LEF1.

159 The NH(2) terminus of LEF1 is frequently mutated in human sebaceous tumors.

160 assays as well as in vitro transfections of LEF1 and beta-catenin show that Dkk4 is a potential down

161 Overexpression of TCF4, but not of TCF3 or LEF1, induced MMP-1, -3, and -13 expression and generic

162 tated LEF/TCF binding elements or by TCF4 or LEF1 mutants.

163 xpression of mammalian beta-cat with TCF4 or LEF1 results in nuclear accumulation of these proteins a

164 ires expression of both beta-cat and TCF4 or LEF1, and is not supported by mutated LEF/TCF binding el

165 mediated transcriptional activation by other LEF1/TCF proteins, the entire hippocampus including the

166 gyrus granule cells, and together with other LEF1/TCF proteins, the development of the hippocampus.

167 ut inhibits transcription by phosphorylating LEF1, a transcriptional activator.

168 logic c-MET up-expression, infra-physiologic LEF1 down-expression and YAP1 signature enrichment as dr

169 uding early T-cell precursor, HOXA-positive, LEF1-inactivated, and TAL1-positive subtypes, which have

170 First, we demonstrate that purified LEF1 protein can interact, in vitro, with consensus LEF1

171 ctor 1 (LEF1) transcription factor, reducing LEF1 responsiveness and enhancer activity in cultured hu

172 ein and mRNA expression, ultimately reducing LEF1 transcriptional activity, as judged by luciferase a

173 a-catenin oligonucleotides that up-regulated LEF1 is not activated by beta-catenin in palate EMT.

174 ession, but we observed that SIRT1 repressed LEF1 protein and mRNA expression, ultimately reducing LE

175 Our data reveal LEF1 as a central regulator of iNKT cell number and Th2-

176 y up-regulated, whereas in BDs, PAX5, Runx2, LEF1, TLE1, and CCND2 were significantly down-regulated.

177 double-nucleotide substitutions in the same LEF1 allele, irrespective of DNA mismatch repair status.

178 Mechanistically, DBC1 stabilizes LEF1-beta-catenin interaction by inhibiting SIRT1-mediat

179 We therefore studied LEF1 expression in 210 adults with CN-AML treated on Ger

180 ranscriptional corepressor CtBP and suppress LEF1/beta-catenin-mediated transcription.

181 nversely, overexpression of HIPK2 suppresses LEF1/beta-catenin-mediated transcriptional activation of

182 of the Wnt receptor FZD2 and the Wnt target LEF1 and decreased expression of Wnt antagonists DKK2 an

183 -catenin level in the cells and enhanced TCF/LEF1 luciferase reporter activity, which could be partia

184 Novel functional TCF/LEF1 binding sites in the promoter regions of fibronecti

185 or to activator, analogous to control of TCF/LEF1.

186 Specific TCF/LEF1 binding sites within the promoter and intron 1 regi

187 ollowed by a decrease in beta-catenin, TCF1, LEF1, Cyclin D1, c-myc, Wnt7a, and PSD95 protein levels

188 oteins (Dkk-1, GSK3beta, beta-catenin, TCF1, LEF1, Cyclin D1, c-myc, Wnt7a, Wnt1, and PSD95) were mea

189 ined LEF1 as a direct target of ERG and that LEF1 inhibition fully abolished ERG-induced Wnt signalin

190 EF1 splicing regulation and demonstrate that LEF1 alternative splicing is a contributing determinant

191 In summary, these studies demonstrate that LEF1 expression is required, but in and of itself is ins

192 in a ferret xenograft model demonstrate that LEF1 is functionally required for submucosal gland forma

193 aken together, our findings demonstrate that LEF1/TCF3 is necessary but not sufficient for TOPGAL act

194 We report here that LEF1 is a new type of target gene ectopically activated

195 To test the hypothesis that LEF1 signaling regulates the fate of the dental epitheli

196 Thus, these results indicate that LEF1 gene expression is attenuated by an antisense non-c

197 We propose that LEF1 NH(2)-terminal mutations play a dual role in skin c

198 In this study, we show that LEF1 and TCF7 (TCF-1) are not only expressed in thymocyt

199 Previous reports showed that LEF1 binds to the MMP13 promoter and transactivates its

200 We showed that LEF1 overexpression in LNCaP cells resulted in increased

201 Our findings suggest that LEF1 inactivation is an important step in the molecular

202 Our studies suggest that LEF1 is a critical survival factor for the dental epithe

203 ansient transfection assays, suggesting that LEF1 is a target of the Wnt pathway in colon cancer.

204 yme in the Lef1 null mutant, suggesting that LEF1 may not affect the cell cycle progression of the mu

205 -regulated genes in primary BL suggests that LEF1 is not only aberrantly expressed but also transcrip

206 The LEF1 gene is aberrantly transcribed in colon cancers bec

207 ty of the osteocalcin promoter; however, the LEF1 recognition site in the osteocalcin promoter was su

208 utant promoter constructs, we identified the LEF1 site in the cyclin D1 promoter as essential for the

209 Mutations in the LEF1-binding site increased the basal activity of the os

210 In a second model, the LEF1 gene was ectopically overexpressed under the direct

211 have shown previously that promoter 1 of the LEF1 gene is activated by T cell factor (TCF)-beta-caten

212 Lef1 and other genes of the LEF1/TCF family of transcription factors are nuclear med

213 the ability of beta-catenin to regulate the LEF1 promoter, and they severely impair the ability of T

214 Surprisingly we found that the LEF1 promoter is selectively activated by specific isofo

215 ptional activator that functions through the LEF1 site and is insensitive to beta-catenin.

216 and in particular, transcription through the LEF1 site as critical for endostatin action in vitro and

217 promoter and facilitates PRC2 binding to the LEF1 promoter and trimethylation of lysine 27 in histone

218 Alternative promoters within the LEF1 locus produce polypeptides of opposing biological a

219 ines identified new LEF1 target genes; these LEF1 targets are enriched with genes associated with can

220 of detectable TOPGAL expression, even though LEF1 was still expressed.

221 a distinct WNT/TCF signaling program through LEF1 and HOXB9 enhances the competence of lung adenocarc

222 Thus, LEF1 regulates the generation of dentate gyrus granule c

223 Unspliced LEF1 NAT interacts with LEF1 promoter and facilitates PR

224 f beta -catenin, but was also dependent upon LEF1/TCF3 in skin.

225 nhanced growth and invasion ability, whereas LEF1 knockdown in LNCaP-AI cells decreased AR expression

226 Whether LEF1 expression associates with clinical and molecular p

227 To determine whether LEF1 expression was sufficient for the induction of airw

228 conferred by beta-catenin's association with LEF1 and BCL9-2/B9L, which accumulate during Wnt stimula

229 ression of MYC and MYC targets in cases with LEF1 inactivation, as well as differentiation arrest at

230 Coexpression of beta-catenin with LEF1 and HDAC1 results in the formation of a beta-cateni

231 onses were still competent to cooperate with LEF1 to activate the c-myc promoter.

232 quires the targeting of its interaction with LEF1 and/or BCL9/B9L, as exemplified by carnosate.

233 Unspliced LEF1 NAT interacts with LEF1 promoter and facilitates PRC2 binding to the LEF1 p

234 Tumour cell lines stably transfected with LEF1(DN) or APC2, or transiently transfected with short-

235 Wnt/LEF1 pathway might provide novel targets for therapeutic

236 Here, we report that ERG activates Wnt/LEF1 signaling cascade through multiple mechanisms.

237 rthermore, functional assays showed that Wnt/LEF1 activation phenocopied that of ERG in inducing cell

238 oblasts induced stromal HA synthesis via Wnt/LEF1 and altered the chemokine profile of stromal fibrob