p53在DNA损伤反应中研究进展.pdfVIP

药学学报 Acta Pharmaceutica Sinica 2011, 46 (12): 1413−1419 ·1413 · ·综述· p53 在DNA 损伤反应中的研究进展 * 王娅杰, 孙 华, 刘耕陶, 陈晓光 ( 中国医学科学院、北京协和医学院药物研究所, 北京 100050) 摘要: p53 基因是研究最广泛的抑癌基因之一, 也是细胞内的一个强大的转录因子, 在正常状态下呈低水平 表达。在各种应激包括 DNA 损伤时, p53 可以被不同的信号通路激活并稳定, 通过增强其下游多种基因的转录而 引起细胞周期阻滞、凋亡或衰老, 保持细胞基因组的完整性并清除损伤细胞, 这些生物学作用取决于不同的应激 信号和细胞类型。p53 通路是机体应对 DNA 损伤的天然防护屏障, 对这一机制的深入研究可为肿瘤的发生发展 和抗肿瘤药物的开发提供重要的信息。 关键词: p53; DNA 损伤; MDM2; ATM 中图分类号: R963 文献标识码: A 文章编号: 0513-4870 (2011) 12-1413-07 Advances in the study of p53 in response to DNA damage * WANG Ya-jie, SUN Hua, LIU Geng-tao, CHEN Xiao-guang (Institute of Materia Medica, Chinese Academy of Medical Sciences Peking Union Medical College, Beijing 100050, China) Abstract : p53 (encoded by TP53) is undoubtedly one of the most extensively studied genes and proteins. It is a highly potent transcription factor which, under normal circumstances, is maintained at low level. Both genotoxic and non-genotoxic stresses can induce p53 stabilized leading to changes in the expression of p53- responsive genes. The biological outcome inducing this pathway can be either growth arrest and apoptosis or senescence to maintain the integrity of the genome or to delete the damaged cells. The biochemical activity of p53 itself and the cellular environment govern the choice between these outcomes in a cell type- and stress-