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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

56 1 but not E2F3, examples where both E2F1 and E2F3 are seen to interact, and promoters that are regula

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

95 3 mutant mice typically die around birth and E2f3-deficient cells have a proliferation defect that co

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

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

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

99 development of these tumorigenic lesions is E2f3 dependent.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

142 E2F3 has garnered particular attention because it is amp

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

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

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

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

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

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

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

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

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

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

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

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

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

156 In contrast, E2f3 inactivation completely suppresses the pulmonary ne

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

158 Ectopic expression of E2F3 induces Aurora-A expression.

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

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

161 E2F3 is an oncogene with strong proliferative potential

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

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

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

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

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

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

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

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

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

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

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

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

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

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

176 amplification showed overexpression of both E2F3 isoforms and CDKAL1.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

192 scribed from an intronic promoter within the E2F3 locus.

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

194 E2f3 loss is sufficient to derepress Arf, triggering act

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

196 E2F3 loss suppresses the development of the pituitary tu

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

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

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

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

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

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

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

204 E2f3 mRNA expression, protein expression, and binding to

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

206 E2F2 and E2F3 mutant backgrounds alleviated Myc proliferative eff

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

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

209 erties of embryonic fibroblasts derived from E2f3 mutant mice.

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

211 significantly increased in both the E2F2 and E2F3 mutants.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

238 transcripts and high levels of expression of E2F3 protein.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

253 This E2f3 TAM gene expression signature was sufficient to pre

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

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

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

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

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

259 00 is in turn directly regulated by Sox2 and E2F3, thereby establishing a unilateral negative feedbac

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

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

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

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

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

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

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

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

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

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

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

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

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

273 E2F3 was recognized as a key facilitator of cell prolife

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

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

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

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

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

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