New developments in the multi-site phosphorylation and integration of stress signalling at p53

Purpose: To summarize recent progress in the understanding of the role of m ulti-site phosphorylation in mediating the integration of stress signals at the p53 tumour suppressor protein. Results: The p53 protein plays a key role in the response to a range of cel lular stresses including agents that can damage DNA; consequently the invol vement of p53 in sensing these effects is central to the prevention of tumo ur development. p53 is a potent but latent transcription factor that can be activated by a range of cellular stresses leading to the induction of cell ular growth arrest or controlled cell removal through apoptosis. Accordingl y, p53 is under tight control and is subject to several levels of regulatio n including multi-site phosphorylation. Recent evidence has implicated indi vidual phosphorylation events in the activation of p53 by different types o f stress (e.g. ionizing radiation, UV and mitotic spindle damage). Conclusions: A picture is now emerging of the p53 protein as an integration point for stress signals. Different signals impinge on different domains o f the protein and may cooperate in modulating the type of p53 response, dep ending on the nature of the incoming signal.