Tumour Suppressor Genes and Molecular Chaperones

The two tumour suppressor genes that are most commonly inactivated in human cancer are the p53 gene on chromosome 17 and the retinoblastoma (Rb) gene on chromosome 11. Recent studies of both gene products suggest that they are able to act as powerful negative regulators of cell division. The Rb gene seems to exert this activity by physically complexing to a variety of specific transcription factors and inactivating their function. The capacity of Rb protein to bind these factors is regulated by phosphorylation. The Rb protein can therefore be seen to act as a chaperone for these factors. The p53 protein also may act in part by regulating transcription but may also interact directly with the DNA replication apparatus. The growth suppressive function of p53 is induced by DNA damage leading to an attractive model of p53 as an essential checkpoint control. The p53 protein interacts with members of the hsp70 chaperone family which we now show can regulate its function.