title: Cell cycle regulation of the E2F transcription factor involves an interaction with cyclin A.
abstract: We have examined E2F binding activity in extracts of synchronized NIH 3T3 cells. During the G0 to G1 transition, there is a marked increase in the level of active E2F. Subsequently, there are changes in the nature of E2F-containing complexes. A G1-specific complex increases in abundance, disappears, and is then replaced by another complex as S phase begins. Analysis of extracts of thymidine-blocked cells confirms that the complexes are cell cycle regulated. We also show that the cyclin A protein is a component of the S phase complex. Each complex can be dissociated by the adenovirus E1A 12S product, releasing free E2F. The release of E2F from the cyclin A complex coincides with the stimulation of an E2F-dependent promoter. We suggest that these interactions control the activity of E2F and that disruption of the complexes by E1A contributes to a loss of cellular proliferation control.
authors.affiliation: Howard Hughes Medical Institute, Department of Microbiology and Immunology, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: M
authors.initials: M
authors.lastname: Mudryj
authors.forename: S H
authors.initials: SH
authors.lastname: Devoto
authors.forename: S W
authors.initials: SW
authors.lastname: Hiebert
authors.forename: T
authors.initials: T
authors.lastname: Hunter
authors.forename: J
authors.initials: J
authors.lastname: Pines
authors.forename: J R
authors.initials: JR
authors.lastname: Nevins
mesh_terms: D017456:Adenovirus Early Proteins; D000818:Animals; D002352:Carrier Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002460:Cell Line; D016213:Cyclins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D050684:E2F Transcription Factors; D046911:Macromolecular Substances; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000235:genetics; D011485:Protein Binding; D056465:Retinoblastoma-Binding Protein 1; D013997:Time Factors; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D017456:Adenovirus Early Proteins; C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D046911:Macromolecular Substances; D009856:Oncogene Proteins, Viral; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors