The p53 tumour suppressor protein is a highly potent transcription factor which, under
normal circumstances, is maintained at low levels through the action of MDM2, an E3
ubiquitin ligase which directs p53 ubiquitylation and degradation. Expression of the mdm2
gene is stimulated by p53 and this reciprocal relationship forms the basis of a negative
feedback loop. Both genotoxic and non-genotoxic stresses that induce p53 focus principally
on interruption of the p53-MDM2 loop with the consequence that p53 becomes stabilised …