The protein encoded by this gene is a negative regulator of the cell cycle and was the first tumor suppressor gene found. The encoded protein also stabilizes constitutive heterochromatin to maintain the overall chromatin structure. The active, hypophosphorylated form of the protein binds transcription factor E2F1. Defects in this gene are a cause of childhood cancer retinoblastoma (RB), bladder cancer, and osteogenic sarcoma.
Rb is a tumor suppressor gene which functions as a negative regulator of the cell cycle by interacting with transcription factors including E2F1, PU1, ATF2, UBF, Elf1 and cAbl. This ability of Rb to alter transcription is regulated by phosphorylation catalyzed by the cyclin dependent protein kinases (cdks). Rb is phosphorylated on serine and threonine, but not on tyrosine residues. It forms a complex with SV40 large T antigen, adenovirus E1A, and human papilloma virus 16E. Rb protein may act by regulating transcription and loss of its function leads to uncontrolled cell growth. Aberrations in the Rb gene have been implicated in cancers of breast, colon, prostate, kidney, nasopharynx, and leukemia.