The Rb protein (pRb, 110kDa) is a tumor suppressor, which plays a pivotal role in the negative control of the cell cycle and in tumor progression. pRb is responsible for a major G1 checkpoint, blocking S-phase entry and cell growth. pRb prevents the cell from replicating damaged DNA by preventing its progression through the cell cycle into its S phase or progressing through G1 phase. pRb can actively inhibit cell cycle progression when it is dephosphorylated while this function is inactivated when pRb is phosphorylated. pRb is activated near the end of mitosis (M phase) when a phosphatase dephosphorylates it, allowing it to bind E2F. The pRb protein represses gene transcription, required for transition from G1 to S phase, by directly binding to the transactivation domain of E2F and by binding to the promoter of these genes as a complex with E2F.