Ubiquitination of p53 and p21 is differentially affected by ionizing and UV radiation.
Levels of the tumor suppressor protein p53 are normally quite low due in part to its short half-life. p53 levels increase in cells exposed to DNA-damaging agents, such as radiation, and this increase is thought to be responsible for the radiation-induced G1 cell cycle arrest or delay. The mechanisms by which radiation causes an increase in p53 are currently unknown. The purpose of this study was to compare the effects of gamma and UV radiation on the stability and ubiquitination of p53 in vivo. Ubiquitin-p53 conjugates could be detected in nonirradiated and gamma-irradiated cells but not in cells which were UV treated, despite the fact that both treatments resulted in the stabilization of the p53 protein. These results demonstrate that UV and gamma radiation have different effects on ubiquitinated p53 and suggest that the UV-induced stabilization of p53 results from a loss of p53 ubiquitination. Ubiquitinated forms of p21, an inhibitor of cyclin-dependent kinases, were detected in vivo, demonstrating that p21 is also a target for degradation by the ubiquitin-dependent proteolytic pathway. However, UV and gamma radiation had no effect on the stability or in vivo ubiquitination of p21, indicating that the radiation effects on p53 are specific.
Maki
C G
CG
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Howley
P M
PM
D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D016213:Cyclins / Q000378:metabolism / Q000528:radiation effects*; D003513:Cycloheximide / Q000494:pharmacology; D004791:Enzyme Inhibitors; D005720:Gamma Rays; D006801:Humans; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000528:radiation effects*; D014452:Ubiquitins / Q000378:metabolism*; D014466:Ultraviolet Rays
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D014452:Ubiquitins; D003513:Cycloheximide; D018844:Cyclin-Dependent Kinases