Stimulation of DNA polymerase alpha activity by Cdk2-phosphorylated Rb protein

We propose a new role of retinoblastoma protein as a cell growth activator in its phosphorylated form. The hyper-phosphorylated retinoblastoma protein generated by the action of cdk2/cyclin E strongly stimulated the activity of DNA polymerase alpha, but did not stimulate DNA polymerases delta, epsil on, or primase. But, cdk4/cyclin D-phosphorylated retinoblastoma protein sh owed little stimulation. Hyper-phosphorylated retinoblastoma protein intera cted with the catalytic subunit of DNA polymerase a; and stabilised DNA pol ymerase or from heat inactivation at 45 degreesC. These results suggest tha t in G1 phase, hypo-phosphorylated retinoblastoma protein suppresses the pr ogression of cell cycle as a transcription inhibitor, but that after phosph orylation by cdk2/cyclin E at the G1/S boundary, hyperphosphorylated retino blastoma protein acts as a cell-cycle promoter by optimising the DNA polyme rase alpha reaction. (C) 2001 Academic Press.