Phosphorylation of E2F-1 modulates its interaction with the retinoblastoma gene product and the adenoviral E4 19 kDa protein.
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.
Fagan
R
R
Laboratory of Gene Regulation, Imperial Cancer Research Fund, London, England.
Flint
K J
KJ
Jones
N
N
D000257:Adenoviridae Infections / Q000378:metabolism; D017504:Adenovirus E4 Proteins / Q000378:metabolism*; D000595:Amino Acid Sequence; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002352:Carrier Proteins; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins; D016213:Cyclins / Q000378:metabolism; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism*; D056465:Retinoblastoma-Binding Protein 1; D012694:Serine / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D017504:Adenovirus E4 Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D014157:Transcription Factors; D012694:Serine; D011494:Protein Kinases; D016203:CDC2 Protein Kinase