mdm2: a bridge over the two tumour suppressors, p53 and Rb

Abstract

The inactivation of the p53 and Rb pathways would account for the majority of human tumours. There are many levels of cross talk between p53 and Rb that have been identified. However, the identification of the mdm2-Rb interaction established a closer link between the two most well studied tumour suppressors, p53 and Rb. Recent studies of the novel trimeric complex Rb-mdm2-p53 provided us with a functional insight of how the two tumour suppressors can act together in regulating p53 induced apoptosis. Beginning with the properties of the Rb-mdm2-p53 trimeric complex, we shall review the propounding evidence suggesting that the apoptotic function of p53 is linked to its transrepression function. The uncoupling of the apoptotic function and transactivation function of p53 will also be discussed.