The retinoblastoma tumor suppressor gene product, known as Rb or pRb, regulates differentiation, apoptosis and cell cycle control by coordinating the cell cycle, at G1/S, with transcriptional machinery that includes the heterodimeric E2F family. During G1, cyclin D (D1, 2, 3)-dependent kinase-mediated phosphorylation of Rb at Ser 795 marks the conversion of Rb from a transcriptionally repressive, hypophosphorylated state to an inactive, phosphorylated state, which may be sustained through mitosis by differential phosphorylation of up to 16 putative serine or threonine residues, including Ser 249/Thr 252, Thr 373, Thr 356, Ser 780, Ser 807/Ser 811 and Thr 821/Thr 826.