Animal cells and systems

  • 제6권3호
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  • Pages.263-269
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  • 2002
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  • 1976-8354(pISSN)
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  • 2151-2485(eISSN)
한국통합생물학회 (The Korean Society for Integrative Biology)
권호 표지

DNA Damage-inducible Phosphorylation of p53 at Ser20 is Required for p53 Stabilization

  • Yang, Dong-Hwa (Department of Life Science, College of Natural Sciences, Sogang University) ;
  • Rhee, Byung-Kirl (Department of Life Science, College of Natural Sciences, Sogang University) ;
  • Yim, Tae-Hee (Department of Life Science, College of Natural Sciences, Sogang University) ;
  • Lee, Hye-Jin (Department of Life Science, College of Natural Sciences, Sogang University) ;
  • Kim, Jungho (Department of Life Science, College of Natural Sciences, Sogang University)
  • 발행 : 2002.09.01
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초록

The p53 tumor suppressor gene is among the most frequently mutated and studied genes in human cancer, but the mechanisms by which it sur presses tumor formation remain unclear. DNA damage regulates both the protein levels of p53 and its affinity for specific DNA sequences. Stabilization of p53 in response to DNA damage is caused by its dissociation from Mdm2, a downstream target gene of p53 and a protein that targets p53 for degradation in the proteosome. Recent studies have suggested that phosphorylation of human p53 at Ser20 is important for stabilizing p53 in response to DNA damage through disruption of the interaction between Mdm2 and p53. We generated mice with an allele encoding changes at Ser20, known to be essential for p53 accumulation following DNA damage, to enable analyses of p53 stabilization in vivo. Our data showed that the mutant p53 was clearly defective for full stabilization of p53 in response to DNA damage. We concluded that Ser20 phosphorylation is critical for modulating the negative regulation of p53 by Mdm2, probably through phosphorylation-dependent inhibition of p53-Mdm2 interaction in the physiological context.

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