Interaction of p27 with E1A and its effect on CDK kinase activity.

The interaction of p27 with adenovirus (Ad) E1A was investigated to study its possible role in cell-cycle regulation and transformation by E1A. In in vitro binding assays, recombinant p27 proteins were shown to bind 12S and 13S E1A products of both Ad12 and Ad5. The amino-terminal region of p27, but not the carboxyl-terminal region, was responsible for the E1A binding. In the Ad12 E1A proteins, the C-terminal region showed relative importance in p27 binding. Phosphorylation of histone H1 or E1A proteins by CDK2 complex was inhibited by p27, but, in contrast, p27 stimulated the phosphorylation of E1A proteins by CDK4. Thus, the interaction of p27 and E1A proteins may modulate the function of E1A in cell-cycle control by regulating E1A phosphorylation. Copyright 1998 Academic Press.