泛素蛋白连接酶MDM2 活性及稳定性调控的研究进展 - 生物通.PDF

HEREDITAS (Beijing) 2009 10 , 31(10): 993―998 ISSN 0253-9772 综 述 DOI: 10.3724/SP.J.1005.2009.00993 泛素蛋白连接酶MDM2 活性及稳定性调控的研究进展 1, 2 2 2 聂晶 , 田春艳 , 张令强 1. , 100084; 2. , , 100850 泛素蛋白连接酶MDM2(Murine double minute 2)具有癌基因活性, MDM2 高表达会导致抑癌基因p53 失 活而诱发肿瘤, 但在至少 7% 的肿瘤中p53 基因正常而 mdm2 异常扩增, 表明 MDM2 还具有其他底物分子, 以 p53 不依赖的方式促进肿瘤的发生。鉴于MDM2 的重要作用, 文章在基因水平、转录水平、翻译后修饰水平、 相互作用分子的调节等方面系统总结了目前对MDM2 调控的主要研究机制及其进展。 MDM2; p53; 癌基因; 翻译后修饰; 蛋白质相互作用; 泛素化降解 Progress in regulation of activity and stability of ubiquitin protein ligase MDM2 1, 2 2 2 NIE Jing , TIAN Chun-Yan , ZHANG Ling-Qiang 1. Department of Biological Sciences and Technology, Tsinghua University, Beijing 100084, China; 2. State Key Laboratory of Proteomics, Beijing Institute of Radiation Medicine, Beijing 100850, China Abstract: The ubiquitin protein ligase (E3) MDM2 (Murine double minute 2) possesses oncogenic activities. Overexpres- sion of this protein enhances degradation and inactivation of the tumor suppressor p53. At least 7% of all human tumors exhibit inappropriate amplification of mdm2, whereas p53 gene remains in its wild-type configuration. This indicates that MDM2 may function in the p53-independent manner to promote tumorigenesis. Considering the critical role of MDM2, this review summarizes the current mechanisms and progress on MDM2 regulation in levels of gene control, mRNA transcrip- tion, post-translational modification, and interaction proteins. Keywords: MDM2; p53; oncogene; post-translational modification; protein interaction; Ub-mediated degradation 1 MDM2 p53 p53 ,