ライフサイエンスコーパス: E2F3

1 onally regulated by the transcription factor E2F3.

2 ression in mice deficient for E2f1, E2f2, or E2f3.

3 fically deficient in binding E2F1, E2F2, and E2F3.

4 es that are distinct from those regulated by E2F3.

5 regulated by the combined action of TFE3 and E2F3.

6 sses the activities of E2F1, but not E2F2 or E2F3.

7 ion is dependent on the marked box domain of E2F3.

8 ssociation between gain of CCND1 and gain of E2F3.

9 and that distinguishes the E2F1 protein from E2F3.

10 ding complexes consisting of pRb and E2F1 or E2F3.

11 cally, dependent on the marked box domain of E2F3.

12 ssion is a specific property of E2F1 and not E2F3.

13 ed in cells deleted for E2F1 but not E2F2 or E2F3.

14 ulation of the cell-cycle regulatory protein E2F3.

15 itical for the activation of the promoter by E2F3.

16 ss the translation of E2F3 by binding to the E2F3 3' untranslated region (UTR) and also enhance the a

17 ough a conserved binding site located in the E2F3 3' untranslated region (UTR).

18 2 genomic clones, most frequently at 6p22.3 (E2F3), 8p12 (FGFR1), 8q22.2 (CMYC), 11q13 (CCND1, EMS1,

19 cond set of experiments, we demonstrate that E2F3 ablation alone does not cause abnormalities in lens

20 E2F3 activated the mitochondrial sensor PPARGC1A in a Cd

21 P = .01), and a gene expression signature of E2F3 activation (P = .03).

22 A promoters, but did not inhibit binding of E2F3 activator to Cyclin B1 promoter.

23 t a critical function of the E2F1, E2F2, and E2F3 activators is in the control of a p53-dependent axi

24 We also find that the acute loss of E2F3 activity affects the expression of genes encoding D

25 Finally, we show that immunodepletion of E2F3 activity inhibits the induction of S phase in proli

26 We propose that E2F3 activity plays an important role during the cell cy

27 t gene of DNA polymerase alpha together with E2F3, again dependent on the E2F3 marked box domain.

28 The combined ablation of E2f1 or E2f3, along with E2f2, did not further accelerate tumori

29 Here we show that E2F3 also has a significant effect on the phenotype of t

30 by markedly reduced levels of expression of E2F3, an E2F family member, and a lack of nuclear locali

31 d pro-tumorigenic transcription factors MYC, E2F3 and AP-1.

32 E2F3 and CDKAL1 are candidate genes from the 6p22 region

33 Trim28 depletion increased E2F3 and E2F4 DNA binding activity, as measured by chrom

34 ocal microscopy indicated co-localization of E2F3 and E2F4 with Trim28 within the cell nucleus, and c

35 on inhibited the transcriptional activity of E2F3 and E2F4, whereas Trim28 deficiency enhanced their

36 strated that the ability of HDAC1 to repress E2F3 and E2F4-driven transcription is dependent on Trim2

37 ssays demonstrated that Trim28 can bind both E2F3 and E2F4.

38 humans, microarray data revealed declines in E2F3 and IGF2 expression with age similar to the mouse.

39 n fetal hepatocytes, which already have high E2f3 and Igf2 expression.

40 wed increased IGF2 expression, and levels of E2F3 and IGF2 mRNA in these cancers were positively corr

41 asts (MEFs), the Arf promoter is occupied by E2F3 and not other E2F family members.

42 neral ability to stably bind E2F1, E2F2, and E2F3 and regulate the cell cycle.

43 e messenger ribonucleic acid (mRNA) encoding E2F3 and significantly reduces the levels of E2F3 protei

44 nding is essential for exerting control over E2F3 and suppressing cell-cycle progression in the prese

45 e that ANCCA directly interacts with E2F1 to E2F3 and that its N terminus interacts with both the N a

46 place miR-17-92 in a regulatory loop between E2F3 and the miR-17 target E2F1.

47 BP to mediate an interaction between E2F2 or E2F3 and YY1 is an important component of Cdc6 activatio

48 uced lineage-negative bone marrow cells from E2F3+/+ and E2F3-/- mice, we show that E2F3 expression i

49 with nerve growth factor (NGF), while E2F1, E2F3, and E2F5 are downregulated.

50 regulated miR-210 expression, down-regulated E2F3, and limited cell proliferation.

51 miRNAs that cooperate with Pumilio to target E2F3, and multiple tumor cell lines shorten the 3' end o

52 ity (E2F2 and E2F4, to a lesser extent E2F1, E2F3, and occasionally E2F5), was constitutively maintai

53 rest is correlated with a reduction in E2F1, E2F3, and p73 levels.

54 CDK4, E2F3, and PPARGC1A levels correlated positively with exe

55 Although growth retarded, surviving E2f3(-/-) animals are initially healthy.

56 Thus, E2F1 and E2F3 appear to play critical, overlapping roles in the d

57 We now demonstrate that E2f1, E2f2, and E2f3 are also required for oncogene-mediated transformat

58 We find that both E2F1 and E2F3 are required for cells to enter the S phase from a

59 1 but not E2F3, examples where both E2F1 and E2F3 are seen to interact, and promoters that are regula

60 cle control, E2f activators (E2f1, E2f2, and E2f3) are portrayed as the ultimate transcriptional effe

61 least two other E2F family members, E2F2 and E2F3, are equally capable of inducing S phase.

62 In summary, these findings identify E2f3 as a key transcription factor in TAMs, which influe

63 /RBP network, together with the discovery of E2F3 as an hnRNP-A1-regulated factor, outlines the relev

64 Another recent study predicted E2F3 as an upstream regulator of the transcriptional res

65 f a synergistic complex between EWS-FLI1 and E2F3 as the by far most likely mechanism explaining the

66 r group predicted transcription factor E2F3 (E2F3) as a prominent upstream regulator of cocaine-induc

67 ipitation assays, we show that both E2F2 and E2F3, as well as YY1 and RYBP, associate with the Cdc6 p

68 t the mRNA encoding the transcription factor E2F3 associates to hnRNP-A1 through a conserved binding

69 Thus, the E2F3-Aurora-A axis could be an important target for canc

70 ncer by immunohistochemistry, including RAS, E2F3, BCL-2 and MCL-1.

71 E2F1, E2F2 and E2F3 belong to a subclass of E2F factors thought to act

72 urthermore, we show that endogenous E2F1 and E2F3 bind to DDB2 promoter and that treatment with E2F1-

73 We find that E2F1, E2F2, and E2F3 bind to the positive-acting E2F site in the cdc2 pr

74 initial G1 following a growth stimulus, only E2F3-binding activity reaccumulates at subsequent G1/S t

75 rmatics analysis revealed the presence of an E2F3-binding site within the CREB promoter, which we val

76 etion of 14-3-3 tau or E2F1, but not E2F2 or E2F3, blocks adriamycin-induced apoptosis.

77 s of E2F1, a domain also present in E2F2 and E2F3 but absent in E2F4 and E2F5, were essential.

78 kinase (TK-1) promoter is also regulated by E2F3 but independent of TFE3.

79 is impaired in the absence of either E2F2 or E2F3 but not E2F1 or E2F4.

80 e expression is dependent on the presence of E2F3 but not E2F1.

81 Accordingly, E2F1 to E2F3 but not E2F4 and E2F5 were found to bind sp1 in vit

82 Consistent with these studies, E2F3, but not E2F1, activates transcription through meth

83 s Pum 1 and Pum 2 repress the translation of E2F3 by binding to the E2F3 3' untranslated region (UTR)

84 tional induction and physical recruitment of E2F3 by EWS-FLI1 replacing E2F4 on their target promoter

85 e posttranscriptional regulation of Sox2 and E2F3 by miR-200 family members might be a general mechan

86 he lack of a negative regulation of Sox2 and E2F3 by miR-200 in conditional Dicer1 mutants (En1(+/Cre

87 V-1 Tat inhibits E2F transcription factor 3 (E2F3), CAMP-responsive element-binding protein (CREB), a

88 It is widely believed that E2F1, E2F2, and E2F3 can all activate cellular proliferation but that E2

89 how that the E2F activators (E2F1, E2F2, and E2F3) can bind to the survivin promoter and induce survi

90 and RYBP, in combination with either E2F2 or E2F3, can stimulate Cdc6 promoter activity synergistical

91 (CAXII) inhibitor and affects apoptotic E2F1/E2F3/Caspase-3 axis by using CAXII esterase activity ass

92 s revealed that there is a selection against E2f3(-/-) cells from developing mammary carcinomas, and

93 cues the known cell cycle re-entry defect of E2f3(-/-) cells, and this correlates with restoration of

94 embryonic stem cells and generated Rb(-/-); E2f3(-/-) chimeric mice, thus bypassing the lethality of

95 is model, we examined the phenotypes of E2f1 E2f3 compound mutant mice.

96 reased nuclear expression of E2F1, E2F2, and E2F3, consistent with regulation of the G1/S phase trans

97 ether with published data on EZH2 and on the E2F3 control protein pRB, we conclude that the pRB-E2F3-

98 cancers of the bone and prostate, activating E2F3 cooperates with ETS on target promoters.

99 explanatory models for the observed EWS-FLI1/E2F3 cooperation based on longitudinal E2F target and re

100 Stable knockdown of E2F3 decreases mRNA and protein levels of Aurora-A and d

101 To determine the molecular consequences of E2F3 deficiency, we analyzed the properties of embryonic

102 3 mutant mice typically die around birth and E2f3-deficient cells have a proliferation defect that co

103 Inactivation of p53 in E2f1-, E2f2-, and E2f3-deficient cells, either by spontaneous mutation or

104 esses the activation of p53 and p21(Cip1) in E2f3-deficient MEFs.

105 E2F3-deficient mice arise at one-quarter of the expected

106 development of these tumorigenic lesions is E2f3 dependent.

107 ranscriptionally induced by DNA damage in an E2f3-dependent manner.

108 l muscle-specific deletion of Cdk4's target, E2F3, depleted oxidative myofibers, deteriorated mitocho

109 ally, whereas embryos lacking both isoforms (E2f3(-/-)) died in utero.

110 rtance for E2F activation, although E2F1 and E2F3 differ in the extent of their ability to activate e

111 Further, E2F3 directly binds to Aurora-A promoter and stimulates

112 E2F transcription factors, including E2F3, directly modulate expression of EZH2.

113 s and gene expression profiling suggest that E2f3 does not impact the proliferation or survival of TA

114 activity, because co-expression of E2F2 and E2F3 does not rescue cells from E2F1-mediated apoptosis.

115 Mutation of E2f3 dramatically impairs the mitogen-induced, transcrip

116 E2F3, we demonstrate that elevated levels of E2F3 drive ectopic proliferation in multiple tissues.

117 nd evidence that E2F transcription factor 3 (E2F3) drives these changes in expression.

118 t Aurora-A is transcriptionally regulated by E2F3 during the cell cycle and that E2F3 is a causal fac

119 e 5' untranslated regions (UTRs) of E2F1 and E2F3 (E2F1/3) mRNAs.

120 rom our group predicted transcription factor E2F3 (E2F3) as a prominent upstream regulator of cocaine

121 oters minimally affects the binding of E2F2, E2F3, E2F4, and E2F5 but significantly inhibits the bind

122 jor difference in the properties of E2F1 and E2F3: either alone or in combination with E2F1 loss, E2f

123 nce of E2F1 and E2F2, however, repression of E2F3 elicits profound reduction of proliferation in the

124 Through the analysis of Rb(-/-);E2f3(+/-) embryos, we have been able to separate E2F3's

125 s viral oncogene homolog) and E2F1, E2F2 and E2F3 (encoding E2F transcription factors 1, 2 and 3, res

126 oteins that includes a role for E2F1 but not E2F3, examples where both E2F1 and E2F3 are seen to inte

127 on profiles that distinguish either E2F1- or E2F3-expressing cells from quiescent cells are enriched

128 Multivariate analyses select E2F3 expression as an independent factor predicting over

129 ing immunohistochemically detectable nuclear E2F3 expression have poorer overall survival (P=0.0022)

130 Knockdown of E2F3 expression in bladder cells containing the 6p22 amp

131 from E2F3+/+ and E2F3-/- mice, we show that E2F3 expression is important for BCR/ABL clonogenic acti

132 te juvenile hepatocytes, restoration of high E2f3 expression restored high Igf2 expression, indicatin

133 Loss of Rb resulted in an increase of E2f3 expression, and the combined ablation of Rb and E2f

134 (P=0.0047) than patients without detectable E2F3 expression.

135 ontrol protein pRB, we conclude that the pRB-E2F3-EZH2 control axis may have a critical role in modul

136 se that the physical interaction of TFE3 and E2F3 facilitates transcriptional activation of the p68 g

137 c-myb and c-myc genes whereas both E2F1 and E2F3 fail to transactivate a reporter gene that is under

138 hat interacts specifically with the E2F2 and E2F3 family members, dependent on the marked box domain

139 the interactions of pRb with E2F1, E2F2, and E2F3 for cell cycle control.

140 Amplification and overexpression of the E2F3 gene at 6p22 in human bladder cancer is associated

141 d mice in which expression of the endogenous E2f3 gene may be either reversibly elevated or repressed

142 n that the expression of the E2F1, E2F2, and E2F3 gene products is tightly regulated by cell growth.

143 hanism controlling the expression of the two E2F3 gene products, we analyzed the genomic sequences fl

144 progression, these results suggest that the E2F3 gene represents a candidate bladder cancer oncogene

145 of RNA expression signatures showed that an E2F3 gene signature was activated in all WT samples anal

146 n human bladder cancer, amplification of the E2F3 gene, located at 6p22, is associated with overexpre

147 E2F3a is one of two splice variants of the E2f3 gene; the other is E2F3b.

148 Indeed, in cells deleted of the E2F1 or E2F3 genes, there is an increase in the expression of th

149 induces transcription of the E2F1, E2F2, and E2F3 genes.

150 thus bypassing the lethality of the Rb(-/-); E2f3(-/-) germ line mutant mice.

151 Whereas the targeted inactivation of E2f1 or E2f3 had no significant effect on tumor progression, los

152 E2F3 has garnered particular attention because it is amp

153 We show that loss of E2F3 has opposing effects on two of the known developmen

154 Transient expression of E2f3 in both HEK293 cells and in late juvenile hepatocyt

155 idered together with the established role of E2F3 in cell cycle progression, these results suggest th

156 ata suggest oncogenic activities of E2F1 and E2F3 in ErbB2- or Myc-triggered mammary tumorigenesis, a

157 but impactful copy number gains in E2F1 and E2F3 in hepatocellular carcinoma (HCC).

158 that E2f3a can fully substitute for E2f1 and E2f3 in most murine tissues.

159 tivator subclass composed of E2f1, E2f2, and E2f3 in mouse embryonic fibroblasts leads to the activat

160 ncy factor Sox2 and the cell-cycle regulator E2F3 in neural stem/progenitor cells.

161 inoma, we show that the specific ablation of E2f3 in TAMs, but not in tumor epithelial cells, attenua

162 observation highlights a potential role for E2F3 in the early stages of this tumor type.

163 Further evaluation defined a key role for E2F3 in the M606-mediated response.

164 autonomous since the inactivation of Rb and E2f3 in TS cells restored placental development and exte

165 To establish the role of E2F3 in vivo, we generated an E2f3 mutant mouse strain.

166 , if any, of E2F proteins, and in particular E2f3, in myogenic differentiation is not well understood

167 In contrast, E2f3 inactivation completely suppresses the pulmonary ne

168 of tumours containing overexpressed nuclear E2F3 increasing with tumour stage and grade.

169 Ectopic expression of E2F3 induces Aurora-A expression.

170 lated by E2F3 during the cell cycle and that E2F3 is a causal factor for up-regulation of Aurora-A in

171 Our results suggest that E2F3 is a key player in neuronal functions and may repre

172 Thus, E2F3 is a key repressor of the p19(Arf)-p53 pathway in n

173 ite retraction, and we also demonstrate that E2F3 is a specific target of miR-34a.

174 E2F3 is an oncogene with strong proliferative potential

175 tingly, Pumilio/miRNA-mediated regulation of E2F3 is circumvented in cancer cells in several differen

176 We conclude that E2F3 is critical for the transcriptional activation of g

177 We find that E2f3 is dispensable for the development of pRB-deficient

178 mor necrosis factor (TNF)-alpha stimulation, E2F3 is dissociated from the promoter and replaced by E2

179 hows that this tumor-suppressive function of E2F3 is dose dependent.

180 We show that E2F3 is essential for embryonic viability in the pure 12

181 f the expected frequency, demonstrating that E2F3 is important for normal development.

182 S phase from a quiescent state, whereas only E2F3 is necessary for the S phase in growing cells.

183 Finally, we show that E2F3 is not required for cellular immortalization but is

184 ng effect, EWSR1/FLI1 binding independent of E2F3 is predominantly associated with repressed differen

185 ro and in vivo approaches, we establish that E2f3 is required for DNA damage-induced apoptosis.

186 omatin immunoprecipitation demonstrates that E2F3 is the primary E2F family member that occupies the

187 this role is largely fulfilled by E2F3b, an E2F3 isoform whose function was previously undetermined.

188 Expression of E2F3 isoforms (E2F3a and b) and CDKAL1 were examined and

189 amplification showed overexpression of both E2F3 isoforms and CDKAL1.

190 Here, we dissect the contributions of E2f3 isoforms and other activating and repressing E2Fs t

191 he effects of overexpression or depletion of E2f3 isoforms in NAc on cocaine behavioral responses.

192 We studied expression of two E2F3 isoforms-E2F3a and E2F3b-in mouse NAc after repeate

193 Moreover, by using shRNA-mediated E2F3 knock-down and BCR/ABL-transduced lineage-negative

194 y analysis on bladder cancer cells following E2F3 knockdown was then used to identify genes regulated

195 interbred MMTV-PyMT mice with E2F1, E2F2, or E2F3 knockout mice.

196 was then used to identify genes regulated by E2F3, leading to the identification of known E2F3 target

197 We found that loss of E2f1 or E2f3 led to a significant delay in tumor onset in both o

198 n together, these observations indicate that E2F3 levels have a critical role in modifying cellular p

199 E2F3 levels were up-regulated in CML-BCCD34+ in a BCR/AB

200 In keratinocytes, knock-down of E2F3 limited cell proliferation.

201 The E2f3 locus encodes E2f3a and E2f3b proteins, and availab

202 The E2f3 locus encodes two isoforms, E2f3a and E2f3b, which

203 We have shown that the E2F3 locus encodes two protein products: the E2F3a produ

204 The E2f3 locus encodes two Rb-binding gene products, E2F3a a

205 scribed from an intronic promoter within the E2F3 locus.

206 oss accelerated tumor growth, while E2F2 and E2F3 loss did not.

207 E2f3 loss is sufficient to derepress Arf, triggering act

208 We show that, instead, E2F3 loss leads to an increase in the rate of tumor init

209 E2F3 loss suppresses the development of the pituitary tu

210 al tumors derived from conditionally deleted E2f3(-/loxP) mammary glands revealed that there is a sel

211 ntrary to the prevailing view of E2F action, E2F3 makes a major contribution to the apoptosis resulti

212 a together with E2F3, again dependent on the E2F3 marked box domain.

213 ectly downregulate MYCN transcription via an E2F3-mediated response represents a potentially valuable

214 ed defects arising in the individual E2f1 or E2f3 mice were exacerbated by the mutation of the other

215 Finally, analysis of Rb(+/-); E2f3(+/-) mice shows that this tumor-suppressive functio

216 -negative bone marrow cells from E2F3+/+ and E2F3-/- mice, we show that E2F3 expression is important

217 Here, we demonstrated that E2F3 modulates Aurora-A mRNA expression during the cell

218 E2f3 mRNA expression, protein expression, and binding to

219 e tumor cell lines shorten the 3' end of the E2F3 mRNA, removing the Pumilio regulatory elements.

220 Here, we identified E2F1 and E2F3 mRNAs as translational targets of WDR77.

221 WDR77 regulated the translation of E2F1 and E2F3 mRNAs through the 5' untranslated regions (UTRs) of

222 E2F2 and E2F3 mutant backgrounds alleviated Myc proliferative eff

223 In this study, we isolated Rb; E2f3 mutant embryonic stem cells and generated Rb(-/-);

224 E2f3 mutant mice typically die around birth and E2f3-def

225 erties of embryonic fibroblasts derived from E2f3 mutant mice.

226 sh the role of E2F3 in vivo, we generated an E2f3 mutant mouse strain.

227 significantly increased in both the E2F2 and E2F3 mutants.

228 Here we show that the E2f3 mutation completely suppresses both the inappropria

229 ther alone or in combination with E2F1 loss, E2f3 mutation did not increase the incidence of tumor fo

230 Representative large-cell genes (E2F3, MYBL2, HDAC2, CDK4, PCNA) are expressed in the nuc

231 probes to show that selective inhibition of E2F3, not global inhibition of E2F activity, significant

232 ow that expression of high levels of nuclear E2F3 occurs in a high proportion (98/147, 67%) of human

233 These results suggest that the E2F3-Oncomir-1 axis is activated in WT.

234 mples to provide the first evidence that the E2F3-Oncomir-1 axis, previously identified in cell cultu

235 r in vivo and that the interaction of either E2F3 or TFE3 with the promoter was facilitated by the pr

236 ecific to E2F1 and was not observed in E2F2, E2F3, or E2F4.

237 In addition, E2F3-overexpressing human prostate and bladder cancers s

238 g relationship between 6p22.3 amplification, E2F3 overexpression and lack of Rb expression.

239 ology to confirm the potential importance of E2F3 overexpression in bladder cancer development.

240 in Igf2 expression in postnatal organs, and E2F3 overexpression in human cancers induces IGF2 overex

241 c prostatic epithelium suggesting a role for E2F3 overexpression in prostate carcinogenesis.

242 of the Rb pathway is required in addition to E2F3 overexpression in this subset of bladder tumours.

243 proliferation index, and in prostate cancer E2F3 overexpression is linked to tumour aggressiveness.

244 Further, we show that miR-34a inhibition or E2F3 overexpression neutralizes Tat's effects and restor

245 We have previously shown that E2F3 plays a critical role in mediating the mitogen-indu

246 ified according to the maximum percentage of E2F3-positive nuclei identified within their prostate ca

247 In addition, expression of E2F3 positively correlates with the protein level of Aur

248 on in Ewing sarcoma we report replacement of E2F3/pRB by constitutively expressed repressive E2F4/p13

249 Importantly, we show that E2F3 promotes proliferation of VSMCs leading to increase

250 rentiation of the SK-N-BE cell line, whereas E2F3 protein levels decrease.

251 Immunohistochemical analyses of E2F3 protein levels have established that around one-thi

252 r and prostate cancer, we have proposed that E2F3 protein overexpression may cooperate with removal o

253 E2F3 and significantly reduces the levels of E2F3 protein, a potent transcriptional inducer of cell-c

254 arcinomas of the bladder overexpress nuclear E2F3 protein, with the proportion of tumours containing

255 transcripts and high levels of expression of E2F3 protein.

256 Both E2F1 and E2F3 proteins have been shown to be particularly importa

257 itical threshold level of one or more of the E2F3-regulated genes determines the timing of the G(1)/S

258 By contrast, E2F3 repression has minimal impact on tissue proliferati

259 The absence of E2F3 results in a significant expansion in the life span

260 the targeted inactivation of E2f1, E2f2, and E2f3 results in elevated p21(CIP1) protein levels, loss

261 NA differs from the previously characterized E2F3 RNA, which we now term E2F3a, by the utilization of

262 nclear how E2f3a versus E2f3b contributes to E2f3's requirement in either proliferation or developmen

263 (+/-) embryos, we have been able to separate E2F3's role in the induction of apoptosis from its abili

264 e we use mutant mouse strains to investigate E2F3's role in vivo.

265 tic tumors (MMP9, CKS2, LRRC15, WNT5A, EZH2, E2F3, SDC1, SKP2, and BIRC5), whereas a candidate tumor

266 ression, and the combined ablation of Rb and E2f3 significantly suppressed Rb mutant phenotypes.

267 ster (P = 0.05) with focal amplifications of E2F3/SOX4, PVRL4, CCNE1, and TP53 mutations.

268 entified the E-box binding factor TFE3 as an E2F3-specific partner.

269 increasingly significant association between E2F3 staining and risk of death both for overall surviva

270 is model system also allows us to assess how E2f3 status influences tumor formation in Rb(-/-) tissue

271 This E2f3 TAM gene expression signature was sufficient to pre

272 ses, we demonstrate that a large fraction of E2F3 target genes are synergistically coregulated by the

273 R) and also enhance the activity of multiple E2F3 targeting microRNAs (miRNAs).

274 E2F3, leading to the identification of known E2F3 targets such as Cyclin A and CDC2 and novel targets

275 of the known E2F activators, E2F1, E2F2, and E2F3, the expression of E2F7 is growth-regulated, at lea

276 Consistent with reduced levels of E2F1 and E2F3, the proliferation of cells defective for p53 funct

277 00 is in turn directly regulated by Sox2 and E2F3, thereby establishing a unilateral negative feedbac

278 cally differentiate the activity of E2F1 and E2F3; this profile is enriched in genes known to functio

279 rectly regulated the in vivo transition from E2F3 to E2F4 as the major E2F DNA binding activity, and

280 p16(INK4A) pulse, abolishing the shift from E2F3 to E2F4, derepressing E2F target genes, and expandi

281 Thus, our data reveal the novel ability of E2f3 to function as a master regulator of the DNA damage

282 sphatase and tensin homolog (PTEN) loss, and E2F3 transcription factor were associated with increased

283 We have found that E2F1 and E2F3, transcription factors that activate genes required

284 -apoptotic E2F1 and toward the proliferative E2F3 transcriptional network.

285 ies suggest that Pumilio-miRNA repression of E2F3 translation provides an important level of E2F regu

286 with overlapping functions (E2F1, E2F2, and E2F3) triggered the p53-p21(Cip1) response and caused ce

287 es we examined the effects of E2f1, E2f2 and E2f3 triple deficiency in murine embryonic stem cells, e

288 te, luciferase reporter assays revealed that E2F3 up-regulates CREB expression and that Tat interfere

289 p73P1 promoter is occupied predominantly by E2F3; upon tumor necrosis factor (TNF)-alpha stimulation

290 ownstream targets of miR-210, namely FGFRL1, E2F3, VMP-1, RAD52 and SDHD, were decreased in the prese

291 Expression of E2F3 was lowest in early-stage tumors and highest in met

292 E2F3 was recognized as a key facilitator of cell prolife

293 y to the key cell cycle transcription factor E2F3, we demonstrate that elevated levels of E2F3 drive

294 unoprecipitation assays showed that TFE3 and E2F3 were bound to the p68 promoter in vivo and that the

295 sequestering E2f activators (E2f1, E2f2 and E2f3), which are invariably portrayed as the ultimate ef

296 We observed that, in contrast to E2F1 and E2F3, which sensitize to death, E2F4 plays a crucial pro

297 xpression that, in turn, silenced its target E2F3, which was markedly down-regulated in the wound-edg

298 the findings suggest that down-regulation of E2f3 with age helps drive the dramatic decline in Igf2 e