Cell cycle regulation of the cyclin A gene promoter is mediated by a variant E2F site.
Cyclin A is involved in the control of S phase and mitosis in mammalian cells. Expression of the cyclin A gene in nontransformed cells is characterized by repression of its promoter during the G1 phase of the cell cycle and its induction at S-phase entry. We show that this mode of regulation is mediated by the transcription factor E2F, which binds to a specific site in the cyclin A promoter. It differs from the prototype E2F site in nucleotide sequence and protein binding; it is bound by E2F complexes containing cyclin E and p107 but not pRB. Ectopic expression of cyclin D1 triggers premature activation of the cyclin A promoter by E2F, and this effect is blocked by the tumor suppressor protein p16INK4.
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000502:physiology; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D019938:Cyclin D1; D051358:Cyclin-Dependent Kinase 4; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018844:Cyclin-Dependent Kinases / Q000502:physiology; D016213:Cyclins / Q000235:genetics* / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D050684:E2F Transcription Factors; D015870:Gene Expression; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D015513:Oncogene Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000235:genetics; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D009838:Oligodeoxyribonucleotides; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D019938:Cyclin D1; C495902:Cdk4 protein, mouse; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases