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D. W. Li, H. Feng, J.-P. Liu, J. Qin, Q. Yan, W.-B. Liu, H.-G. Chen, Y.-M. Xiao, Y. Liu; Protein Phosphatase-1 Dephosphorylates P53 at Ser-20 and Ser-46 to Modulate Its Stability & Transcriptional Activities. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5645.
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We have previously demonstrated that the serine/threonine protein phosphatase-1 (PP-1) can directly dephosphorylate p53, a master regulator of apoptosis at Ser-15 and Ser-37 to modulate its transactivity and proapoptotic abilities to prevent apoptosis (Li et al., Oncogene, 2006). In the present study, we provide evidence to show that PP-1 can also directly dephosphorylate p53 at Ser-20 and Ser-46 to negatively modulate its stability & transcriptional activity.
Dephosphorylation of p53 by protein phosphatase-1 was explored with in vitro dephosphorylation assay, co-localization and in vivo dephosphorylation assays. The stability of both wild type and mutant p53 and their functions in regulating gene expression was analyzed with RT-PCR, Western blot analysis, and reporter activity assay.
Besides Ser-15 and Ser-37, PP-1 can also directly dephosphorylate p53 at Ser-20 and Ser-46 as demonstrated with co-immunoprecipitation, co-localization, in vitro and in vivo dephosphorylation assays, overexpression and silence of the gene encoding the catalytic subunit for PP-1.
Dephosphorylation of p53 by PP-1 has as important impact on its functions as phosphorylation does. One of the molecular mechanisms by which PP-1 promotes cell survival is derived from its ability to dephosphorylate p53 at multiple residues, and thus negatively regulate p53-dependent death pathway.
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