泛素介导的蛋白质降解系统——从基础研究到临床应用.pdfVIP

第22卷 第3期 生命科学 Vol. 22, No. 3 2010年3月 Chinese Bulletin of Life Sciences Mar., 2010 文章编号 ：1004-0374(2010)03-0212-04 泛素介导的蛋白质降解系统——从基础研究到临床应用 Aaron Ciechanover (以色列工学院医学科学研究所) 摘 要：20 世纪60~80 年代，大多数生物科研人员都致力于核酸和遗传信息传递的研究。蛋白质降解 被认为是非特异的过程，因此没有人感兴趣。泛素修饰的发现使蛋白质降解领域发生革命性的变化， 人们逐渐认识到蛋白质降解是一个特异的受严格调控的过程。细胞内蛋白质降解事件的发生会调节许多 生命过程，如细胞增殖、分化、衰老和死亡。细胞内蛋白质降解调控异常也会引发多种疾病，包括 癌症和神经退行性疾病。人们对细胞内蛋白质降解的研究已经取得一定成果，但是还有很多问题没有解 决，全面解读该过程还需要更多的努力和探索。 关键词：泛素；蛋白酶体；蛋 白质降解；癌症 中图分类号：Q591.2；R730.231.3　　文献标识码：A The ubiquitin proteolytic system – from bench to the bedside Aaron Ciechanover (Medicine Technion-Israel Institute of Technology, Haifa, Israel) Abstract: Between the sixties and eighties, most life scientists focused their attention on studies of nucleic acids and the translation of the coded information. Protein degradation was a neglected area, considered to be a non- specific, dead-end process. While it was known that proteins do turnover, the large extent and high specificity of the process-whereby distinct proteins have half-lives that range from a few minutes to several days- was not appreciated. The discovery of the complex cascade of ubiquitin pathway revolutionized the field. The high complexed, temporarily controlled and tightly regulated process of protein degradation plays major role in a variety of basic pathways during cell life and death. Aberrations in this pathway are implicated in the pathogen- esis of many diseases, certain malignancies and neurodegeneration among them. Despite intensive research, the unknown still exceeds what we currently know on intracellular protein degradation process. More effort is needed. Key wor