Active transcriptional repression by the Rb-E2F complex mediates G1 arrest triggered by p16INK4a, TGFbeta, and contact inhibition.
Rb inhibits progression from G1 to S phase of the cell cycle. It associates with a number of cellular proteins; however, the nature of these interactions and their relative significance in cell cycle regulation are still unclear. We present evidence that Rb must normally interact with the E2F family of transcription factors to arrest cells in G1, and that this arrest results from active transcriptional repression by the Rb-E2F complex, not from inactivation of E2F. Thus, a major role of E2F in cell cycle regulation is assembly of this repressor complex. We demonstrate that active repression by Rb-E2F mediates the G1 arrest triggered by TGFbeta, p16INK4a, and contact inhibition.
Zhang
H S
HS
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Postigo
A A
AA
Dean
D C
DC
D000818:Animals; D002352:Carrier Proteins; D002450:Cell Communication / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000502:physiology*; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D016193:G1 Phase / Q000235:genetics / Q000502:physiology*; D006131:Growth Inhibitors / Q000502:physiology; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000502:physiology*; D016160:Retinoblastoma Protein / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014407:Tumor Cells, Cultured
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D006131:Growth Inhibitors; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D016212:Transforming Growth Factor beta