RB1 and neoplasm: P21Cip1 which halts the cell cycle in the G1 phase by binding to and inactivating cyclin-CDK complexes is also a negative regulator of cell cycle progression and a typical tumor suppressor gene [33]. After the inhibition of protein kinase activity in cyclin-CDK complexes by p27Kip1 and p21Cip1, Rb is in a state of hypophosphorylation.