REGULATION OF THE RETINOBLASTOMA PROTEIN-RELATED PROTEIN P107 BY G(1)CYCLIN-ASSOCIATED KINASES

p107 is a retinoblastoma protein-related phosphoprotein that, when ove rproduced, displays a growth inhibitory function. It interacts with an d modulates the activity of the transcription factor, E2F-4. In additi on, p107 physically associates with cyclin E-CDK2 and cyclin A-CDK2 co mplexes in late G(1) and at G(1)/S, respectively, an indication that c yclin-dependent kinase complexes may regulate, contribute to, and/or b enefit from p107 function during the cell cycle. Our results show that p107 phosphorylation begins in mid Ct and proceeds through late G(1) and S and that cyclin D-associated kinase(s) contributes to this proce ss. In addition, E2F-4 binds selectively to hypophosphorylated p107, a nd G(1) cyclin-dependent p107 phosphorylation leads to the dissociatio n of p107-E2F-4 complexes as well as inactivation of p107 G(1) blockin g function.