CELL CYCLE-DEPENDENT PHOSPHORYLATION OF THE TUMOR-SUPPRESSOR RB PROTEIN

Cell cycle-dependent phosphorylation of the RE protein plays a key rol e in the regulation of cellular proliferation, At least three kinds of cyclin-dependent kinases (Cdks), including cyclin D/Cdk6 or Cdk4, cyc lin E/Cdk2 and cyclin A/Cdk2, are involved in the phosphorylation of t he RE protein at G1/S border. These G1 cyclin/Cdks seem to be the foca l target of carcinogenesis signals. Multistep carcinogenesis could be also explained based on this hypothesis. Thus, G1 cyclin/Cdks are good target for discovery of anti-cancer drugs.