RB1 (retinoblastoma protein) is a key regulator of the entry into cell division and acts as a tumor suppressor. RB1 inactivation leads to retinoblastoma cancer. In normal cells, RB1 promotes the G0-G1 transition when phosphorylated by CDK3/cyclin-C and acts as a transcription repressor of E2F1 target genes. The underphosphorylated, active form of RB1 interacts with E2F1 and represses its transcription activity, leading to cell cycle arrest. It is directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. In case of viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity. In immunohistochemistry of normal tissue, RB1 has nuclear positivity in the retina and most tissues. References: The UniProt Consortium. Nucleic Acids Res. 47: D506-515 (2019); Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45, PMID:26553804; Clinical Cancer Research. 19 (15): 4040–5, PMID: 23719267;