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J Mol Biol. 1996 Oct 25;263(2):103-13.

How phosphorylation regulates the activity of p53.

Author information

1
Laboratory of Molecular Carcinogenesis, Sylvius, Laboratories, Leiden University, The Netherlands.

Abstract

P53 is of key importance for the protection of an organism against carcinogenesis. P53 performs this function by the regulation of several cellular processes, the most important of which are apoptosis and cell-cycle progression. P53 controls these processes most likely through the transcriptional regulation of target genes, such as those for p21waf1 and bax. Since p53 is involved in the regulation of these distinct processes, the protein should be able to respond quickly to environmental changes. P53 is a phosphoprotein phosphorylated on multiple sites by a variety of kinases. The two main phosphorylation domains are the N and the C terminus. The N-terminal part contains the transcription-regulatory domain of p53, while the C-terminal domain controls the specific DNA binding by p53. Here we present an overview of the kinases known to phosphorylate p53 and the effects of phosphorylation on biochemical and biological functions. The picture that emerges shows that phosphorylation of p53 on specific sites can modulate the activity of the protein, either by affecting its abundance, the affinity for its DNA-consensus sequence or the activity of the transcription-activation domain. Furthermore, the kinases involved are downstream targets of different inducers, such as DNA-damage/stress inducers and mitogens, giving the cell the opportunity to respond to distinct extracellular stimuli via modulation of p53 activity.

PMID:
8913292
DOI:
10.1006/jmbi.1996.0560
[Indexed for MEDLINE]

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