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The classic review of the brakes on the cell cycle, the proteins that hold back the cyclin-dependent kinases which commit a cell to dividing, and how cancers lose them, the biology behind today's CDK4/6 inhibitors.
Sherr and Roberts described the two families of cyclin-dependent kinase inhibitors that govern passage through G1: the INK4 proteins (p16, p15, p18 and p19), which specifically block cyclin D-CDK4 and CDK6, and the Cip/Kip proteins (p21, p27 and p57), which act on a broader range of cyclin-CDK complexes. They explained how these inhibitors integrate mitogenic and anti-proliferative signals to control the restriction point, how p21 links p53 to arrest and p27 mediates contact inhibition and TGF-beta responses, and how loss of p16 or p27 and overexpression of cyclin D contribute to cancer.
This review is the textbook basis for the cyclin D-CDK4/6-RB axis that palbociclib, ribociclib and abemaciclib target in breast cancer, and for reading CDKN2A loss and cyclin D1 amplification in tumour genomes.
Shares Tumour suppressor gene, The cell-cycle engine (cyclins & CDKs), CDK4/6, CDK4/6 inhibitors.
Shares El-Deiry 1993: WAF1, the gene through which p53 stops cell division, Cell cycle, Tumour suppressor gene, p53 / RB / cell-cycle checkpoint.
Shares CDK4/6, p53 / RB / cell-cycle checkpoint.
Shares CDK4/6, p53 / RB / cell-cycle checkpoint.
Shares CDK4/6, CDK4/6 inhibitors.
Shares CDK4/6, CDK4/6 inhibitors.
Shares CDK4/6, p53 / RB / cell-cycle checkpoint.
Shares CDK4/6, CDK4/6 inhibitors, p53 / RB / cell-cycle checkpoint.