title: E2F4 and E2F5 play an essential role in pocket protein-mediated G1 control.
abstract: E2F transcription factors are major regulators of cell proliferation. The diversity of the E2F family suggests that individual members perform distinct functions in cell cycle control. E2F4 and E2F5 constitute a defined subset of the family. Until now, there has been little understanding of their individual biochemical and biological functions. Here, we report that simultaneous inactivation of E2F4 and E2F5 in mice results in neonatal lethality, suggesting that they perform overlapping functions during mouse development. Embryonic fibroblasts isolated from these mice proliferated normally and reentered from Go with normal kinetics compared to wild-type cells. However, they failed to arrest in G1 in response to p16INK4a. Thus, E2F4 and E2F5 are dispensable for cell cycle progression but necessary for pocket protein-mediated G1 arrest of cycling cells.
authors.affiliation: The Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: S
authors.initials: S
authors.lastname: Gaubatz
authors.forename: G J
authors.initials: GJ
authors.lastname: Lindeman
authors.forename: S
authors.initials: S
authors.lastname: Ishida
authors.forename: L
authors.initials: L
authors.lastname: Jakoi
authors.forename: J R
authors.initials: JR
authors.lastname: Nevins
authors.forename: D M
authors.initials: DM
authors.lastname: Livingston
authors.forename: R E
authors.initials: RE
authors.lastname: Rempel
mesh_terms: D000483:Alleles; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D050704:E2F4 Transcription Factor; D050700:E2F5 Transcription Factor; D005347:Fibroblasts / Q000166:cytology; D016193:G1 Phase / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D011905:Genes, ras / Q000502:physiology; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D011506:Proteins; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology; D014162:Transfection
chemical_list: D002352:Carrier Proteins; C493957:Cdkn1a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D050704:E2F4 Transcription Factor; D050700:E2F5 Transcription Factor; C490490:E2f5 protein, mouse; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; C489485:Rbl1 protein, mouse; C493838:Rbl2 protein, mouse; D016160:Retinoblastoma Protein; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D014157:Transcription Factors