Rb Background Information Pediatric cancer retinoblastoma and the formation of other human tumors can be attributed to mutations in the retinoblastoma tumor suppressor gene (Rb) (1,2). The Rb protein regulates differentiation, apoptosis, and cell cycle control by coordinating the cell cycle at G1-S with transcriptional machinery (3,4). During G1, cyclin D-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 (2,4–7). Hypophosphorylated Rb represses the transcription of genes controlling the cell cycle through direct protein-protein interactions and through the recruitment of histone deacetylase (8,9).
