Cyclin A-kinase regulation of E2F-1 DNA binding function underlies suppression of an S phase checkpoint

Cell. 1995 Dec 29;83(7):1149-58. doi: 10.1016/0092-8674(95)90141-8.

Abstract

Commitment of mammalian cells to enter S phase enables the transcription factor E2F-1 to activate certain genes whose products mediate cell cycle advance. In S phase, E2F-1 forms stable complexes with cyclin A-kinase, which in turn eliminates E2F-1DNA binding function. Here, we show that suppression of E2F-1 DNA-binding activity by cyclin A-kinase is linked to orderly S phase progression. Disruption of this linkage resulted in S phase delay/arrest followed by regrowth or apoptosis, depending upon whether the DNA-bound E2F-1 could transactivate. Hence, the unscheduled presence of E2F-1 on specific DNA sequences during S phase can activate a specific S phase checkpoint, thereby linking transcription, DNA replication, and cell cycle control.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells / cytology
  • Animals
  • Apoptosis / physiology
  • Blood Proteins / pharmacology
  • Carrier Proteins*
  • Cell Cycle Proteins*
  • Cell Division / genetics
  • Cell Survival / physiology
  • Cell Transformation, Neoplastic
  • Cyclin-Dependent Kinases* / physiology*
  • Cyclins / physiology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Fibroblasts / cytology
  • Mice
  • Mice, Nude
  • Mutation / physiology
  • Phosphorylation
  • Retinoblastoma-Binding Protein 1
  • S Phase / physiology*
  • Transcription Factor DP1
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation

Substances

  • Arid4a protein, mouse
  • Blood Proteins
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cyclins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2f1 protein, mouse
  • Retinoblastoma-Binding Protein 1
  • Transcription Factor DP1
  • Transcription Factors
  • Cyclin-Dependent Kinases