Abstract
CENTRAL to the role of p53 in cell regulation are its sequence-specific interactions with genes that control the cell cycle and apoptosis1,2. p53 response elements contain two or more copies of a somewhat promiscuous consensus sequence: 5′-XXXC(A,T)(T,A)GYYY-3′ (where X is a purine and Y is a pyrimidine) (ref. 3). The sequence-specific DNA-binding region of p53 resides in its central conserved region4. Although this region itself is not known to be phosphorylated, the amino and carboxy termini of human p53 contain sites for phosphorylation by several protein kinases. We have examined the role of cyclin-dependent kinase (Cdk) shown previously to phosphorylate human p53 at serine 315 (ref. 5). We report here that p53 is efficiently and selectively phosphor-ylated by S and G2/M Cdks. Such phosphorylation markedly stimulates sequence-specific DNA binding by p53 and also causes a distinctive conformational change in p53 as revealed by partial protease analysis. Strikingly, Cdk phosphorylation also confers binding-site preference on p53. These data suggest a potential regulatory mechanism of p53 activity.
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Wang, Y., Prives, C. Increased and altered DNA binding of human p53 by S and G2/M but not Gl cyclin-dependent kinases. Nature 376, 88–91 (1995). https://doi.org/10.1038/376088a0
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DOI: https://doi.org/10.1038/376088a0
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