Guardavaccaro Daniele, Pagano Michele
Department of Pathology and NYU Cancer Institute, MSB 599, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Oncogene. 2004 Mar 15;23(11):2037-49. doi: 10.1038/sj.onc.1207413.
Accumulating evidence points to a key role of the ubiquitin-proteasome pathway in oncogenesis. Aberrant proteolysis of substrates involved in cellular processes such as the cell division cycle, gene transcription, the DNA damage response and apoptosis has been reported to contribute significantly to neoplastic transformation. Cullin-dependent ubiquitin ligases (CDLs) form a class of structurally related multisubunit enzymes central to the ubiquitin-mediated proteolysis of many important biological substrates. In this review, we describe the role of CDLs in the ubiquitinylation of cancer-related substrates and discuss how altered ubiquitinylation by CDLs may contribute to tumor development.
越来越多的证据表明泛素-蛋白酶体途径在肿瘤发生中起关键作用。据报道，参与细胞分裂周期、基因转录、DNA损伤反应和细胞凋亡等细胞过程的底物异常蛋白水解对肿瘤转化有显著贡献。依赖Cullin的泛素连接酶（CDLs）形成一类结构相关的多亚基酶，是许多重要生物底物泛素介导的蛋白水解的核心。在本综述中，我们描述了CDLs在癌症相关底物泛素化中的作用，并讨论了CDLs改变的泛素化如何可能促进肿瘤发展。
