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 interac tion with a spectrum of cellular proteins. One such protein is the pro duct of the retinoblastoma gene (Rb); association of E2F with Rb inhib its its transactivation potential. However, in adenovirus-infected cel ls, 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 33 2 and 337 prevented its interaction with Rb but was a prerequisite for interaction with E4. These residues were phosphorylated in vivo and b y p34(cdc2) kinase in vitro. Upon stimulation of serum-starved cells, phosphorylation was induced in the late G1 phase of the cell cycle. Th ese observations suggest that phosphorylation of E2F-1 is important in the regulation of its activity during the cell cycle and during infec tion of cells tay adenovirus.