Cell cycle regulation of the E2F transcription factor involves an interaction with cyclin A.
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.
Mudryj
M
M
Howard Hughes Medical Institute, Department of Microbiology and Immunology, Duke University Medical Center, Durham, North Carolina 27710.
Devoto
S H
SH
Hiebert
S W
SW
Hunter
T
T
Pines
J
J
Nevins
J R
JR
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*
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