The regulation of p53 synthesis.

The regulation of p53 expression levels is critical in controlling p53 activity in normal and damaged cells. This is well illustrated by the E3 ubiquitin ligase MDM2 that targets p53 for proteasomal degradation under normal conditions and is essential for controlling p53 activity during development. MDM2 is over-expressed in human cancers and together with some other E3 ligases that have also been implicated in controlling p53 stability, which emphasises the importance of post-translational regulation of p53 expression. At the level of synthesis, TP53 mRNA levels do not change in response to stresses and it is instead its rate of translation initiation that provides the mechanism of choice for expression control. More recent work has shown that TP53 mRNA plays an important role in mediating the cellular regulation of p53 activity. We will discuss the regulation of p53 synthesis and its implications for controlling p53 activity under normal conditions and during different types of stress response.