Phosphorylation of E2F-1 modulates its interaction with the retinoblastoma gene product and the adenoviral E4 19 kDa protein

Cell. 1994 Sep 9;78(5):799-811. doi: 10.1016/s0092-8674(94)90522-3.

Abstract

The transcription factor E2F is regulated through its cyclical interaction with a spectrum of cellular proteins. One such protein is the product of the retinoblastoma gene (Rb); association of E2F with Rb inhibits its transactivation potential. However, in adenovirus-infected cells, E2F is complexed to the 19 kDa product of the adenovirus E4 gene. We have studied the interaction of E2F-1 with the Rb and adenovirus E4 proteins and show that phosphorylation of E2F-1 on serine residues 332 and 337 prevented its interaction with Rb but was a prerequisite for interaction with E4. These residues were phosphorylated in vivo and by p34cdc2 kinase in vitro. Upon stimulation of serum-starved cells, phosphorylation was induced in the late G1 phase of the cell cycle. These observations suggest that phosphorylation of E2F-1 is important in the regulation of its activity during the cell cycle and during infection of cells by adenovirus.

Publication types

  • Comparative Study

MeSH terms

  • Adenoviridae Infections / metabolism
  • Adenovirus E4 Proteins / metabolism*
  • Amino Acid Sequence
  • CDC2 Protein Kinase / metabolism
  • Carrier Proteins*
  • Cell Cycle / physiology
  • Cell Cycle Proteins*
  • Cyclins / metabolism
  • DNA-Binding Proteins*
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Binding
  • Protein Kinases / metabolism
  • Retinoblastoma Protein / metabolism*
  • Retinoblastoma-Binding Protein 1
  • Serine / metabolism
  • Transcription Factors / metabolism*

Substances

  • Adenovirus E4 Proteins
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cyclins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Retinoblastoma Protein
  • Retinoblastoma-Binding Protein 1
  • Transcription Factors
  • Serine
  • Protein Kinases
  • CDC2 Protein Kinase