Maki C G, Howley P M
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Mol Cell Biol. 1997 Jan;17(1):355-63. doi: 10.1128/MCB.17.1.355.
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.
肿瘤抑制蛋白p53的水平通常相当低，部分原因是其半衰期较短。在暴露于DNA损伤剂（如辐射）的细胞中，p53水平会升高，这种升高被认为是辐射诱导的G1期细胞周期停滞或延迟的原因。目前尚不清楚辐射导致p53升高的机制。本研究的目的是比较γ射线和紫外线辐射对体内p53稳定性和泛素化的影响。尽管两种处理都导致p53蛋白稳定，但在未照射和γ射线照射的细胞中可检测到泛素-p53缀合物，而在紫外线处理的细胞中则未检测到。这些结果表明，紫外线和γ射线对泛素化p53有不同的影响，并表明紫外线诱导的p53稳定是由于p53泛素化的丧失。在体内检测到细胞周期蛋白依赖性激酶抑制剂p21的泛素化形式，表明p21也是泛素依赖性蛋白水解途径的降解靶点。然而，紫外线和γ射线对p21的稳定性或体内泛素化没有影响，表明辐射对p53的影响是特异性的。
