PHOSPHORYLATION AT THE CARBOXY-TERMINUS OF THE 55-KILODALTON ADENOVIRUS TYPE-5 E1B PROTEIN REGULATES TRANSFORMING ACTIVITY

The 55-kDa product of early region 1B (E1B) of human adenoviruses is r equired for viral replication and participates in cell transformation through complex formation with and inactivation of the cellular tumor suppressor p53. We have used both biochemical and genetic approaches t o show that this 496-residue (496R) protein of adenovirus type 5 is ph osphorylated at serine and threonine residues near the carboxy terminu s within sequences characteristic of substrates of casein kinase II. M utations which converted serines 490 and 491 to alanine residues decre ased viral replication and greatly reduced the efficiency of transform ation of primary baby rat kidney cells. Such mutant 496B proteins inte racted with p53 at efficiencies similar to those of wild-type 496R but only partially inhibited p53 transactivation activity. These results indicated that phosphorylation at these carboxy-terminal sites either regulates the inhibition of p53 or regulates some other 496R function required for cell transformation.