ライフサイエンスコーパス: E2F2

1 vivo corneal endothelium that overexpressed E2F2.

2 by either assay in cells that overexpressed E2F2.

3 ress due to dysregulated DNA replication via E2F2.

4 o redundancy of adult function with E2F1 and E2F2.

5 E2A binding site within the first intron of E2F2.

6 e targets including the cell cycle regulator E2F2.

7 expression, is rescued by miR-24-insensitive E2F2.

8 The E2F2 3'UTR lacks a predicted miR-24 recognition element.

9 E2F2, a related E2F family member that does not induce a

10 ificant effect on tumor progression, loss of E2f2 accelerated lymphomagenesis.

11 et in both oncogenic models, whereas loss of E2f2 accelerated mammary tumorigenesis driven by Myc-ove

12 and promoter-reporter assays indicated that E2F2 activates ECE-1b transcription.

13 liferation is reduced in mice lacking either E2F2 alone or both E2F2 and E2F3a, but not in mice lacki

14 Interestingly, loss of a single copy of E2f2 also accelerated tumorigenesis, albeit to a lesser

15 reas Mip130 (Lin9) (an MMB core protein) and E2f2 (an MMB transcriptional repressor) are not, but are

16 he absence of p19ARF following expression of E2F2, an E2F family member that does not induce apoptosi

17 pRB proteins are inactivated, expression of E2F2 and -3a was increased.

18 shift the A2-protein complexes, whereas anti-E2F2 and 6 antibodies cannot, demonstrating that the A2

19 ults in an increase in affinity for E2F1 and E2F2 and an increase in the ability of p107 to inhibit E

20 ytomatosis viral oncogene homolog) and E2F1, E2F2 and E2F3 (encoding E2F transcription factors 1, 2 a

21 E2F1, E2F2 and E2F3 belong to a subclass of E2F factors though

22 N terminus of E2F1, a domain also present in E2F2 and E2F3 but absent in E2F4 and E2F5, were essentia

23 survival activity, because co-expression of E2F2 and E2F3 does not rescue cells from E2F1-mediated a

24 protein that interacts specifically with the E2F2 and E2F3 family members, dependent on the marked bo

25 E2F1 loss accelerated tumor growth, while E2F2 and E2F3 loss did not.

26 E2F2 and E2F3 mutant backgrounds alleviated Myc prolifer

27 ound and significantly increased in both the E2F2 and E2F3 mutants.

28 E2f alleles we examined the effects of E2f1, E2f2 and E2f3 triple deficiency in murine embryonic stem

29 nding and sequestering E2f activators (E2f1, E2f2 and E2f3), which are invariably portrayed as the ul

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

31 mmunoprecipitation assays, we show that both E2F2 and E2F3, as well as YY1 and RYBP, associate with t

32 ed in mice lacking either E2F2 alone or both E2F2 and E2F3a, but not in mice lacking E2F1.

33 ressing T antigen contain abundant levels of E2F2 and E2F3a.

34 2F DNA binding activity, composed largely of E2F2 and E2F4, and the growth-suppressive E2F4-p130 comp

35 lanoma cells, free E2F DNA binding activity (E2F2 and E2F4, to a lesser extent E2F1, E2F3, and occasi

36 plasmid containing full-length cDNA for both E2F2 and EGFP (pIRES2-E2F2/EGFP).

37 ICC demonstrated the colocalization of E2F2 and EGFP in corneal endothelium with a transfection

38 subunit of the PRC2 complex, as well as the E2F2 and FOXM1 transcriptional networks.

39 E3(-) adenovirus incorporating cDNA encoding E2F2 and green fluorescent protein (GFP) under control o

40 und by a Myb-containing or alternatively, an E2f2 and L(3)mbt form of the complex.

41 lar endothelial growth factor receptor/FLT1, E2F2 and PCM1 oncogenes were highly enriched in ovarian

42 miR-24 directly regulates MYC and E2F2 and some genes that they transactivate.

43 ough the ability of Rb to bind and sequester E2F2 and the ability of E2F8 to compete with E2F2 for E2

44 s a repressor of transcription, dependent on E2F2 and the RBFs.

45 several key cell-cycle regulators including E2F2, and chromatin immunoprecipitation assays detected

46 ed expression of SV40 T-antigen (TAg), human E2F2, and dominant negative Sprouty2 (dn-Spry2) genes to

47 uggest that a critical function of the E2F1, E2F2, and E2F3 activators is in the control of a p53-dep

48 rom its general ability to stably bind E2F1, E2F2, and E2F3 and regulate the cell cycle.

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

50 We find that E2F1, E2F2, and E2F3 bind to the positive-acting E2F site in t

51 It is widely believed that E2F1, E2F2, and E2F3 can all activate cellular proliferation b

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

53 k has shown that the expression of the E2F1, E2F2, and E2F3 gene products is tightly regulated by cel

54 on factor induces transcription of the E2F1, E2F2, and E2F3 genes.

55 ire E2F activator subclass composed of E2f1, E2f2, and E2f3 in mouse embryonic fibroblasts leads to t

56 ated that the targeted inactivation of E2f1, E2f2, and E2f3 results in elevated p21(CIP1) protein lev

57 an cell cycle control, E2f activators (E2f1, E2f2, and E2f3) are portrayed as the ultimate transcript

58 We also show that the E2F activators (E2F1, E2F2, and E2F3) can bind to the survivin promoter and in

59 activators with overlapping functions (E2F1, E2F2, and E2F3) triggered the p53-p21(Cip1) response and

60 F also increased nuclear expression of E2F1, E2F2, and E2F3, consistent with regulation of the G1/S p

61 xpression of the known E2F activators, E2F1, E2F2, and E2F3, the expression of E2F7 is growth-regulat

62 54W) specifically deficient in binding E2F1, E2F2, and E2F3.

63 past experiments, it appears that the E2F1, E2F2, and E2F3a genes are similarly regulated by growth

64 nto either transcriptional activators (E2F1, E2F2, and E2F3a) or repressors (E2F3b, E2F4, E2F5, E2F6,

65 in the generally repressive Drosophila RBF, E2F2, and Myb (dREAM)/Myb-MuvB complex.

66 r Kruppel-like factor, MEF2C, ETS, NFY, ATF, E2F2, and NRF1 transcription factors in determining tran

67 s induces expression of cyclin D1, E2F1, and E2F2, and promotes proliferation.

68 ore resistant to apoptosis in the absence of E2f2, and the reintroduction of E2F2 into these tumor ce

69 Inactivation of p53 in E2f1-, E2f2-, and E2f3-deficient cells, either by spontaneous m

70 o the regulation of myogenic function, while E2f2 appears to be less important.

71 Furthermore, we demonstrate that E2F1 and E2F2 are transcriptionally induced by DNA damage in an E

72 rs, Mip120 (Myb-interacting protein 120) and E2F2, are required for repression of Gr63a in inappropri

73 y modulates viral replication and identifies E2F2 as a possible target for antiviral therapies.

74 PT inhibitor identified transcription factor E2F2 as the center of a transcriptional hub in the NAD(+

75 th the critical regulator of the cell cycle, E2f2, at a hub.

76 vation of Rb and E2f8 synergizes to increase E2F2 binding to its target gene promoters.

77 in immunoprecipitation assays confirmed that E2F2 binds the ECE-1b promoter, and promoter-reporter as

78 of pRb/p130 upregulated islet expression of E2F2 but not E2F1.

79 Transfection with cyclin D1 or E2F2, but not cyclin E or activated Akt, overcame the ra

80 e also led to reduced expression of E2F1 and E2F2, but not E2F4, at the mRNA and protein levels.

81 onizing miR-24 is abrogated by knocking down E2F2, but not MYC, and cell proliferation, inhibited by

82 Expression of either E2F1 or E2F2 can induce postmitotic lens fiber cells to re-enter

83 e of both Myb and Mip130, or of both Myb and E2F2, caused variegated expression in which high or low

84 prominent nodes at genes that enhance (MYC, E2F2, CCNB1, and CDC2) or inhibit (p27Kip1 and VHL) cell

85 Human E2F1 and E2F2 cDNAs were linked to the alphaA-crystallin promoter

86 tingly, real-time quantitative PCR (qPCR) on E2F2 ChIPs indicated that inactivation of Rb and E2f8 sy

87 omic sequences flanking the 5' region of the E2F2 coding sequence.

88 and other data now link together the Myb and E2F2 complexes in higher-order assembly to specific chro

89 Thus, E2F2 converted PC12-derived neurons from a reversible to

90 feration in a PI3K/Akt/GSK3beta/beta-catenin/E2F2-dependent manner and modulated the cell size increa

91 urthermore, mice deficient for both E2F1 and E2F2 develop nonautoimmune, insulin-dependent diabetes w

92 ombined ablation of E2f1 or E2f3, along with E2f2, did not further accelerate tumorigenesis.

93 In addition, E2F1/E2F2 DKO mice do not recover normal T cell numbers follo

94 in expression of N-Myc target genes ODC1 and E2F2 DOT1L bound to the Myc Box II domain of N-Myc prote

95 E2F1/E2F2 double knockout (DKO) T cells enter S phase in resp

96 from E2F1 knockout (E2F1(-/-)) and E2F1 and E2F2 double knockout (E2F1(-/-)E2F2(-/-)) mice than isog

97 ntly, hematopoietic defects observed in E2F1/E2F2 double-knockout (DKO) mice appear to result from im

98 Importantly, we show that E2F1 and E2F2 double-knockout T cells exhibit more rapid entry in

99 In Drosophila melanogaster the E2f1, E2f2, Dp, and Rbf1 genes all contribute to replication c

100 es are elevated compared to the wild type in E2f2, Dp, and Rbf1 mutant follicle cells.

101 Mutation of E2f2, Dp, or Rbf1 causes ectopic DNA replication through

102 We found that E2F2, DP, RBF1, RBF2, and the Drosophila homolog of LIN-

103 t RBF1 forms complexes with both E2F1/DP and E2F2/DP that cooperate to repress the expression of pre-

104 ularly in the HCCs, of pRb-free E2F1-DP1 and E2F2-DP1 transcription factor heterodimers, as assessed

105 Downstream, E2F2 drives the transcription of members of the inhibito

106 b promoters minimally affects the binding of E2F2, E2F3, E2F4, and E2F5 but significantly inhibits th

107 was specific to E2F1 and was not observed in E2F2, E2F3, or E2F4.

108 on of the entire subset of activators, E2f1, E2f2, E2f3a and E2f3b, singly or in combination in mice.

109 l-length cDNA for both E2F2 and EGFP (pIRES2-E2F2/EGFP).

110 site counters the repression activity of the E2F2 element in young leaves.

111 in the bone marrow of mice lacking E2F1 and E2F2 exhibit increased cell cycling.

112 ressed cell-cycle regulators including E2F1, E2F2, EXO1, FOXM1, and MCM2.

113 quence that reproduces the normal control of E2F2 expression during a growth stimulation.

114 vels through the use of siRNA confirmed that E2F2 expression facilitated HPV replication but its loss

115 h doxycycline significantly reduced ODC1 and E2F2 expression, reduced tumor progression, and improved

116 helial surface was used to image recombinant E2F2 expression.

117 ion, beta-catenin nuclear translocation, and E2F2 expression.

118 ype tissue, whereas restoration of Mip130 or E2F2 extinguished Polo expression.

119 E2F2 and the ability of E2F8 to compete with E2F2 for E2f-binding sites on target gene promoters.

120 hopenic conditions, suggesting that E2F1 and E2F2 function redundantly downstream of TCR and/or IL-7

121 These data indicate that E2f2 functions to inhibit widespread genomic DNA synthes

122 rrelated with high levels of MYCN, ODC1, and E2F2 gene expression and independently correlated with p

123 on and N-Myc protein binding at the ODC1 and E2F2 gene promoters and reduced neuroblastoma cell proli

124 n vivo functions of the transcription factor E2F2 have not previously been analyzed or described in t

125 In the absence of E2F1 and E2F2, however, repression of E2F3 elicits profound reduc

126 The identification of a NAMPT-E2F2-ID axis establishes a link between NAD(+) metabolis

127 The loss of E2F1 and E2F2 impedes B-cell differentiation, and hematopoietic p

128 Here, we investigated the potential role of E2F2 in blood pressure regulation.

129 showed that overexpression of either E2F1 or E2F2 in lens fiber cells was sufficient to cause cell cy

130 We show that the combined loss of E2F1 and E2F2 in mice leads to profound cell-autonomous defects i

131 umorigenesis, and a tumor suppressor role of E2F2 in Myc-mediated mammary tumorigenesis.

132 re we have specifically examined the role of E2F2 in neuronal differentiation using a gain-of-functio

133 Overexpression of the transcription factor E2F2 in nonmitotic human corneal endothelial cells resul

134 Overexpression of the transcription factor E2F2 in nonproliferating rabbit corneal endothelial cell

135 ive and memory T cells lacking both E2F1 and E2F2 in response to lymphopenic conditions, suggesting t

136 results indicate specific roles for E2F1 and E2F2 in the induction of E2F target genes, which contrib

137 C) localization tested for overexpression of E2F2 in transfected corneal endothelial cells and permit

138 Endogenous E2F2 increased in PC12 cells in response to nerve growth

139 increase in a PI3K/Akt/GSK3beta/beta-catenin/E2F2-independent manner.

140 vealed that it proceeded in a p53, E2F1, and E2F2-independent manner.

141 or potentiated (ex vivo) by loss of E2F1 and E2F2, indicating divergent requirements for these E2F fa

142 entry upon NGF removal, forced expression of E2F2 inhibited these events and induced apoptosis.

143 In contrast, neither E2F1 nor E2F2 interacted with the p68 promoter under these condit

144 e absence of E2f2, and the reintroduction of E2F2 into these tumor cells resulted in an increase of a

145 Therefore, E2F2 is a critical miR-24 target.

146 Accordingly, we demonstrate E2F2 is required for GSC self-renewal.

147 We show that loss of E2f2 is viable, but causes partial female sterility asso

148 (PCNA) and showed that the proximal element (E2F2) is required for the full repression of PCNA expres

149 xpression data from tumors revealed that the E2F2 knockout background resulted in fewer tumors with E

150 circulating tumor cells in both the E2F1 and E2F2 knockout backgrounds.

151 reduction in circulating tumor cells in the E2F2 knockout.

152 Furthermore, loss or downregulation of E2F2 led to a decline in ECE-1b levels, to higher levels

153 Reduction of E2F2 levels through the use of siRNA confirmed that E2F2

154 n and outgrowth were markedly inhibited when E2F2 levels were reduced.

155 These results identify the E2f2 locus as a tumor suppressor through its ability to

156 dependent activation and modification of the E2f2 locus is required for cell cycle progression preced

157 These results indicate that E2F2 may have a unique role in maintaining the postmitot

158 hroid terminal differentiation by preventing E2F2-mediated aberrant transcriptional activation throug

159 pathways and upregulation of the FOXM1- and E2F2-mediated cell cycle transitions, as well as epigene

160 hromatin immunoprecipitation), and repressed E2F2-mediated ECE-1b promoter activity (promoter-reporte

161 and in ex vivo ring assays, aortas from the E2F2(-/-) mice exhibited significantly greater contracti

162 e ECE-1 isoform, were significantly lower in E2F2(-/-) mice than in wild-type mice.

163 ures were significantly higher in E2F2-null (E2F2(-/-)) mice than in their wild-type littermates, and

164 and E2F1 and E2F2 double knockout (E2F1(-/-)E2F2(-/-)) mice than isogenic wild-type MEFs.

165 etic system that is also defective in E2f1-/-E2f2-/-mice The demonstration that beta cell maintenance

166 row can prevent or rescue diabetes in E2f1-/-E2f2-/-mice.

167 ex was sensitive to the dose of the subunits E2F2, Mip120, Caf1, and Lin-52 but not Mip130 or Mip40.

168 E2f2 mRNA and protein levels were markedly decreased in

169 E2f2 mutant females display a 50% reduction in chorion g

170 The ectopic genomic replication of E2f2 mutant follicle cells can be suppressed by reducing

171 RT-PCR analyses of RNA purified from E2f2 mutant follicle cells indicate an increase in the l

172 E2f2 mutant follicle cells terminate endocycles on sched

173 Consistent with these observations, E2F1/E2F2 mutant mice are highly predisposed to the developme

174 Pancreatic exocrine cells in E2f1-/-E2f2 mutant mice become increasingly polyploid with age,

175 E2F2 mutant mice show erythroid maturation defects that

176 E2f1/E2f2 mutant mice transplanted with wild-type, but not ma

177 roughout the entire follicle cell nucleus in E2f2 mutants, consistent with their use at many genomic

178 ntent in both Rbf1 and Dp mutants but not in E2f2 mutants.

179 onal derepression is greater in Rbf1 than in E2f2 mutants.

180 2 mutants was indistinguishable from that of E2F2 mutants.

181 As reported previously for the E2F2 mutation, the E2F1 and E2F1+2 mutations partially r

182 In fact, miR-24 regulates expression of E2F2, MYC, AURKB, CCNA2, CDC2, CDK4, and FEN1 by recogni

183 omised in E2f1 null mice but not affected in E2f2 null mice.

184 blood pressures were significantly higher in E2F2-null (E2F2(-/-)) mice than in their wild-type litte

185 Finally, Sam68 coimmunoprecipitated with E2F2, occupied the ECE-1b promoter (chromatin immunoprec

186 ty of RYBP to mediate an interaction between E2F2 or E2F3 and YY1 is an important component of Cdc6 a

187 S phase is impaired in the absence of either E2F2 or E2F3 but not E2F1 or E2F4.

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

189 on, YY1 and RYBP, in combination with either E2F2 or E2F3, can stimulate Cdc6 promoter activity syner

190 nd represses the activities of E2F1, but not E2F2 or E2F3.

191 ly reduced in cells deleted for E2F1 but not E2F2 or E2F3.

192 asis, we interbred MMTV-PyMT mice with E2F1, E2F2, or E2F3 knockout mice.

193 umor progression in mice deficient for E2f1, E2f2, or E2f3.

194 p14(ARF) promotes p53 activity, and E2F2 overexpression in p53 wild-type cells normally lead

195 Moreover, the relative action of RB versus E2F2 overexpression on specific genes demonstrates that

196 phosphorylation (PSM-RB) when compared with E2F2 overproduction.

197 st cancer we found that a low probability of E2F2 pathway activation was associated with increased re

198 Thus, E2F1 and E2F2 play essential and redundant roles in the proper co

199 Furthermore, T cells lacking E2F1 and E2F2 proliferate much more extensively in response to su

200 demonstrated EKLF occupancy at the proximal E2f2 promoter in vivo.

201 ells, E7 acts to inhibit HDAC binding to the E2F2 promoter resulting in activation of expression.

202 hromatin modifier, EKLF binding sites in the E2f2 promoter were located in a region of EKLF-dependent

203 ells, similar to the control of the E2F1 and E2F2 promoters.

204 s, a Tax-associated increase in steady-state E2F2 protein was also documented.

205 se microRNAs reduced the levels of c-Myc and E2F2 proteins.

206 E2F2, RBF, and Mip130/LIN-9 acted in opposition to Myb b

207 of gene expression by Myb, Mip130/LIN-9, and E2F2-RBF in vivo, and also provide an explanation for th

208 Collectively, we demonstrate that IFI6, via E2F2 regulates DNA replication and melanoma development

209 a cell-cycle-independent mechanism by which E2F2 regulates endothelial function, arterial contractil

210 idating in this context that upregulation of E2F2 represents a key intermediate event in a HER2 oncog

211 In contrast, E2F1 and E2F2 repressors function redundantly for some genes in t

212 Remarkably, inactivation of E2f2 rescued the erythropoietic defects resulting from R

213 Compared with the control, transduction with E2F2 resulted in progression from the G(1) to the S phas

214 We show that the combined loss of E2F1 and E2F2 results in profound effects on hematopoietic cell p

215 t overexpression of the transcription factor E2F2 results in replication in nonproliferating human co

216 ls in S phase, the combined loss of E2F1 and E2F2 results in significantly decreased expression and a

217 kingly, it was observed that loss of E2F1 or E2F2 significantly reduced the metastatic capacity of th

218 element (E2F1) and how it interacts with the E2F2 site to regulate the PCNA promoter.

219 E2F1 or E2F2 stimulated bICP0 early promoter activity at least 1

220 cient for the transcription factors E2F1 and E2F2 suffer from a chronic pancreatitis-like syndrome an

221 he absence of other E2F activators, E2f1 and E2f2, suggesting that these isoforms have redundant func

222 Absence of the dREAM subunit Mip130 or E2F2 suppressed the Myb-null cytokinesis defect.

223 3-fold increase) in cells that overexpressed E2F2 than in control samples.

224 elative functional contributions of E2F1 and E2F2 to gene expression and cell cycle control depends o

225 is induction is the ability of E2F1, and not E2F2, to upregulate Chk2 expression.

226 n increase in the ability of p107 to inhibit E2F2 transactivation.

227 roto-oncogene, upregulates expression of the E2F2 transcription factor.

228 r studies of mice deficient for the E2F1 and E2F2 transcription factors have revealed essential roles

229 E7 was found to specifically activate E2F2 transcription in suprabasal keratinocytes through i

230 The Drosophila Myb oncoprotein, the E2F2 transcriptional repressor, and the RBF and Mip130/L

231 y (E)15.5, strong expression of the E2F1 and E2F2 transgenes was detected in lens fiber cells with li

232 At many of these sites, E2F2 was critical for repression, whereas at other nonov

233 Expression of either E2F1 or E2F2 was sufficient to induce the transcription of cycli

234 majority of these genes, including E2f1 and E2f2, was abolished in muscles lacking satellite cell ac

235 The E2F3a increase, but not that of E2F2, was dependent on E2F1.

236 the E2F transcription factor family (E2f and E2f2), which controls the expression of genes that regul

237 ession signature--including STAT1, CD74, and E2F2--which strongly correlates with the magnitude of th