The tumour suppressor protein p53 is a critical inhibitor of cancer, whose functions are enhanced by interactions with vital protein partners including the Promyelocytic leukemia protein (PML; as we and others have demonstrated (Alsheich-Bartok, Haupt et al. 2008)). p53 malfunction is a feature of cancers, which occurs either through mutation or deregulation of its pathways at near equal incidence. Mutation of p53 can lead not only to the loss of its tumour suppressive functions, but also to the gain of new oncogenic functions. Unexpectedly, we have demonstrated that when p53 is mutated it insidiously corrupts the tumour suppressive activity of its partner PML to promote its aberrant functions. Importantly, mutant p53 cancer cells actually become dependent on PML, identifying a potential therapeutic opportunity where PML down regulation can inhibit growth and promote cell death in multiple mutant p53 cancer cell lines (Haupt, di Agostino et al. 2009). Another level of fundamental interdependence is that wild-type p53 is a transcriptional regulator of PML (de Stanchina, Querido et al. 2004). We are now examining the repercussions of p53 mutation on PML expression and how this impacts on cancer cell growth.