The retinoblastoma protein and cell cycle control

Pathology and genetics of tumors of soft tissue and bone

The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53

The cell cycle is composed of a series of steps which can be negatively or positively regulated by various factors. Chief among the negative regulators is the p53 protein. Alteration or inactivation of p53 by mutation, or by its interactions with oncogene products of DNA tumour viruses, can lead to cancer. These mutations seem to be the most common genetic change in human cancers.

The p53 tumour suppressor gene

Tumour-associated cell cycle defects are often mediated by alterations in cyclin-dependent kinase (CDK) activity. Misregulated CDKs induce unscheduled proliferation as well as genomic and chromosomal instability. According to current models, mammalian CDKs are essential for driving each cell cycle phase, so therapeutic strategies that block CDK activity are unlikely to selectively target tumour cells. However, recent genetic evidence has revealed that, whereas CDK1 is required for the cell cycle, interphase CDKs are only essential for proliferation of specialized cells. Emerging evidence suggests that tumour cells may also require specific interphase CDKs for proliferation. Thus, selective CDK inhibition may provide therapeutic benefit against certain human neoplasias.

Cell cycle, CDKs and cancer: a changing paradigm

https://www.cell.com/cell/pdf/0092-8674(88)90559-4.pdf

Chun-Ming Huang

Papers

SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene

The product of the retinoblastoma susceptibility gene has properties of a cell cycle regulatory element.

SV40 large T antigen binds preferentially to an underphosphorylated member of the retinoblastoma susceptibility gene product family.