Dose-dependent UV Stabilization of p53 in Cultured Human Cells Undergoing Apoptosis Is Mediated by Poly(ADP-ribosyl)ation

  • Won, Jungyeon (Department of Biological Sciences, Korea Advanced Institute of Science and Technology) ;
  • Chung, So Young (Department of Biological Sciences, Korea Advanced Institute of Science and Technology) ;
  • Kim, Seung Beom (Department of Biological Sciences, Korea Advanced Institute of Science and Technology) ;
  • Byun, Boo Hyeong (College of Oriental Medicine, Daegu Haany University) ;
  • Yoon, Yoo Sik (Department of Medical Research and Development, Korea Institute of Oriental Medicine) ;
  • Joe, Cheol O. (Department of Biological Sciences, Korea Advanced Institute of Science and Technology)
  • Received : 2005.10.24
  • Accepted : 2005.12.19
  • Published : 2006.04.30

Abstract

The effect of poly(ADP-ribosyl)ation on the stability of p53 in SK-HEP1 cells treated with UV light was examined. Intracellular levels of p53 increased in cells treated with a low dose of UV light ($20J/m^2$), whereas they increased but then declined after a higher dose of UV ($100J/m^2$). Intracellular levels of p53 in the UV treated SK-HEP1 cells were dependent on the UV dose. Use of proteasome inhibitors revealed that p53 is degraded by proteasomal proteolysis after high doses of UV light. We present evidence that, at low doses, poly(ADP-ribose)polymerase (PARP) poly(ADP-ribosyl) ates p53 and protects it from proteasomal degradation before caspase-3 is activated, whereas at high doses the cells undergo UV induced apoptosis and PARP is cleaved by caspase-3 before it can protect p53 from degradation. Destabilization of p53 by cleavage of PARP may be important in cell fate decision favoring apoptosis.

Keywords

Apoptosis;Caspase-3;p53;PARP;Proteasome;UV

Acknowledgement

Supported by : National Cancer Center, Korea Research Foundation

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