- RB, the retinoblastoma protein, has been identified as a crucial tumour suppressor. It is believed to be directly or indirectly inactivated in nearly all human cancers.
- RB has been demonstrated to bind to over one hundred protein partners and has been shown to mediate transcriptional regulation of hundreds of target genes. These protein partners and transcriptional targets are thought to mediate the numerous cellular functions of RB, including temporary and permanent cell cycle arrest, genomic stability, apoptosis and differentiation.
- The cellular functions of RB, as well as a potential role in angiogenesis and metastasis, might contribute to its role as a tumour suppressor, but it is currently unknown which function is most critical. Distinct cellular functions of RB might contribute to its role in preventing tumour initiation versus its role in preventing tumour progression.
- The function of RB that is crucial for tumour suppression might also depend on in which type of cell RB is lost — stem cell, progenitor or differentiated cell — as well as in which tissue.
- In some contexts, presence of RB during earlier stages might be beneficial to tumour progression. Effects of post-translational modifications of RB on individual cellular functions might contribute to preference for a tumour to mutate RB or an upstream regulator.
Deborah L. Burkhart & Julien Sage, Cellular mechanisms of tumour suppression by the retinoblastoma gene, September 2008 Vol 8 No 9, doi:10.1038/nrc2399 [link]