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Enhancement of the antiproliferative function of p53 by phosphorylation at serine 20: an inference from site-directed mutagenesis studies

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Recent studies have shown that Ser20 of p53 is phosphorylated in vivo in response to DNA damage caused by ionizing radiation (IR) or ultraviolet radiation (UV), treatments that also result in the induction of p21WAF1/Cip1 (p21) expression. We hypothesized that Ser20 phosphorylation enhances the transactivation function of p53. To test this, we generated two p53 mutants, changing the Ser residue to either Ala, an uncharged form that may mimic unphosphorylated p53, or to Asp, a negatively charged form that may mimic constitutively phosphorylated p53. p53-null cells transfected with the Ser20 phosphorylation-mimicking mutant p53Asp20 demonstrated heightened p21 expression and reduced cell proliferation relative to wild-type p53-transfected cells. Moreover, p53Asp20 exhibited reduced capacity to interact with the Mdm-2 protein in vitro. This abridged interaction had no effect, however, on p53 protein stability. These results suggest that the phosphorylation of p53 at Ser20 is an important mechanism in the activation of the p53/p21 cell-growth inhibitory pathways in response to DNA damage by IR and UV.
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Document Type: Research Article

Affiliations: Department of Pathology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA

Publication date: January 1, 2001

More about this publication?
  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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