Dose-dependent UV stabilization of p53 in cultured human cells undergoing apoptosis is mediated by poly(ADP-ribosyl)ation

Mol Cells. 2006 Apr 30;21(2):218-23.


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 (20 J/m2), whereas they increased but then declined after a higher dose of UV (100 J/m2). 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • Caspase 3 / metabolism
  • Cells, Cultured / radiation effects*
  • Dose-Response Relationship, Radiation
  • Enzyme Activation
  • Humans
  • Poly (ADP-Ribose) Polymerase-1
  • Poly Adenosine Diphosphate Ribose / metabolism*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proteasome Endopeptidase Complex / metabolism
  • Proteasome Inhibitors
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Ultraviolet Rays


  • Proteasome Inhibitors
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Poly Adenosine Diphosphate Ribose
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • Caspase 3
  • Proteasome Endopeptidase Complex