HOW PHOSPHORYLATION REGULATES THE ACTIVITY OF P53

P53 is of key importance for the protection of an organism against car cinogenesis. P53 performs this function by the regulation of several c ellular processes, the most important of which are apoptosis and cell- cycle progression. P53 controls these processes most likely through th e transcriptional regulation of target genes, such as those for p21(wa f1) and bar. Since p3 is involved in the regulation of these distinct processes, the protein should be able to respond quickly to environmen tal changes. P53 is a phosphoprotein phosphorylated on multiple sites by a variety of kinases. The two main phosphorylation domains are at t he N and the C terminus. The N-terminal part contains the transcriptio n-regulatory domain of p53, while the C-terminal domain controls the s pecific DNA binding by p53. Here we present an overview of the kinases known to phosphorylate p3 and the effects of phosphorylation on bioch emical and biological functions. The picture that emerges shows that p hosphorylation of p53 on specific sites can modulate the activity of t he protein, either by affecting its abundance, the affinity for its DN A-consensus sequence or the activity of the transcription-activation d omain. Furthermore, the kinases involved are downstream targets of dif ferent inducers, such as DNA-damage/stress inducers and mitogens, givi ng the cell the opportunity to respond to distinct extracellular stimu li via modulation of p53 activity. (C) 1996 Academic Press Limited