Dial 9-1-1 for p53: Mechanisms of p53 activation by cellular stress

The tumor suppressor protein, p53, is part of the cell's emergency team tha t is called upon following cellular insult. How do cells sense DNA damage a nd other cellular stresses and what signal transduction pathways are used t o alert p53? How is the resulting nuclear accumulation of p53 accomplished and what determines the outcome of p53 induction? Many posttranslational mo difications of p53, such as phosphorylation, dephosphorylation, acetylation and ribosylation, have been shown to occur following cellular stress. Some of these modifications may activate the p53 protein, interfere with MDM2 b inding and/or dictate cellular localization of p53, This review will focus on recent findings about how the p53 response may be activated following ce llular stress.