Role for E2F in DNA damage-induced entry of cells into S phase

Cancer Res. 1997 Sep 1;57(17):3640-3.

Abstract

Mammalian cells respond to ionizing radiation (IR) with transient cell cycle arrest and induction of apoptosis. Here we show that IR increases the expression of the E2F-1 transcription factor and the entry of cells into S phase. E2F-1 transactivation function is inhibited by cyclin A-kinase to ensure orderly progression through S phase. However, in contrast to proliferating cells, IR treatment results in down-regulation of cyclin A-kinase. Expression of a dominant negative form of the E2F heterodimeric partner DP-1 confirmed the involvement of E2F in IR-induced S-phase entry. These findings also support opposing signals involving the induction of E2F and the down-regulation of cyclin A-kinase in the IR response.

Publication types

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

MeSH terms

  • Apoptosis
  • Carrier Proteins*
  • Cell Cycle Proteins / metabolism
  • Cell Cycle Proteins / radiation effects*
  • DNA / metabolism*
  • DNA Damage*
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / radiation effects*
  • Down-Regulation
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Flow Cytometry
  • G1 Phase / genetics
  • HL-60 Cells / metabolism
  • HL-60 Cells / radiation effects
  • Humans
  • Protein Kinases / metabolism
  • Protein Kinases / radiation effects*
  • RNA, Messenger / metabolism
  • Retinoblastoma-Binding Protein 1
  • S Phase / genetics*
  • Transcription Factor DP1
  • Transcription Factors / metabolism
  • Transcription Factors / radiation effects*

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • RNA, Messenger
  • Retinoblastoma-Binding Protein 1
  • TFDP1 protein, human
  • Transcription Factor DP1
  • Transcription Factors
  • DNA
  • Protein Kinases
  • histone H1 kinase