Tumour suppression by p53: the importance of apoptosis and cellular senescence

p53 is regarded as a central player in tumour suppression, as it controls programmed cell death (apoptosis) as well as cellular senescence. While apoptosis eliminates cells at high risk for oncogenic transformation, senescence acts as a barrier to tumourigenesis by imposing irreversible cell cycle arrest. p53 can act directly or indirectly at multiple levels of the tumour suppression network by invoking a myriad of mechanisms. p53 induces the extrinsic and intrinsic apoptotic pathways at multiple steps to ensure an efficient death response. This response involves transcriptional activation or repression of target genes, as well as the recently identified microRNAs, and transcription-independent functions. Importantly, p53 loss of function is required for tumour maintenance. Therefore, therapeutic strategies aimed at reactivation of p53 in tumours emerge as a promising approach for the treatment of cancer patients. Copyright (C) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.