Residues phosphorylated by TFIIH are required for E2F-1 degradation during S-phase

EMBO J. 1999 Aug 2;18(15):4280-91. doi: 10.1093/emboj/18.15.4280.

Abstract

The transcription factor E2F-1 plays a key role in regulating cell cycle progression. Accordingly, E2F-1 activity is itself tightly controlled by a series of transcriptional and post-transcriptional events. Here we show that the E2F-1 activation domain interacts with a kinase activity which phosphorylates two sites, Ser403 and Thr433, within the activation domain. We demonstrate that TFIIH is responsible for the E2F-1 phosphorylation observed in cell extracts and that endogenous E2F-1 interacts in vivo with p62, a component of TFIIH, during S phase. When the two phosphorylation sites in E2F-1 are mutated to alanine, the stability of the E2F-1 activation domain is greatly increased. These results suggest that TFIIH-mediated phosphorylation of E2F-1 plays a role in triggering E2F-1 degradation during S phase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Carrier Proteins*
  • Cell Cycle Proteins*
  • Cell Line
  • DNA-Binding Proteins*
  • Drosophila Proteins*
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • HeLa Cells
  • Humans
  • Hydrolysis
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Binding
  • Protein Kinases / metabolism
  • Retinoblastoma-Binding Protein 1
  • S Phase*
  • Sequence Homology, Amino Acid
  • Serine / metabolism
  • Threonine / metabolism
  • Trans-Activators*
  • Transcription Factor DP1
  • Transcription Factor TFIIH
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*
  • Transcription Factors, TFII*
  • Transcription, Genetic

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Dp transcription factor, Drosophila
  • Drosophila Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Retinoblastoma-Binding Protein 1
  • Trans-Activators
  • Transcription Factor DP1
  • Transcription Factors
  • Transcription Factors, TFII
  • Transcription Factor TFIIH
  • Threonine
  • Serine
  • Protein Kinases