P06400

Rb is a negative regulator of the cell cycle and was the first tumor suppressor gene found. Rb 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, D2, D3)-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. Hypophosphorylated Rb represses transcription of genes controlling cell cycle through direct protein-protein interactions, by binding and inactivating promoters of transcription factors, and through recruitment of histone deacetylase, which deacetylates promoter regions and enhances nucleosome formation, thereby masking transcription enhancing cis elements.