de la Vega Michelle, Burrows James F, Johnston James A
Centre for Infection and Immunity; School of Medicine, Dentistry and Biomedical Sciences; Queen's University; Belfast, UK.
Small GTPases. 2011 Jul;2(4):192-201. doi: 10.4161/sgtp.2.4.16707. Epub 2011 Jul 1.
The regulation of the small GTPases leading to their membrane localization has long been attributed to processing of their C-terminal CAAX box. As deregulation of many of these GTPases have been implicated in cancer and other disorders, prenylation and methylation of this CAAX box has been studied in depth as a possibility for drug targeting, but unfortunately, to date no drug has proved clinically beneficial. However, these GTPases also undergo other modifications that may be important for their regulation. Ubiquitination has long been demonstrated to regulate the fate of numerous cellular proteins and recently it has become apparent that many GTPases, along with their GAPs, GeFs and GDis, undergo ubiquitination leading to a variety of fates such as re-localization or degradation. in this review we focus on the recent literature demonstrating that the regulation of small GTPases by ubiquitination, either directly or indirectly, plays a considerable role in controlling their function and that targeting these modifications could be important for disease treatment.
长期以来，人们一直认为小GTP酶向膜定位的调节归因于其C末端CAAX盒的加工。由于这些GTP酶中的许多失调与癌症和其他疾病有关，因此对该CAAX盒的异戊二烯化和甲基化作为药物靶点的可能性进行了深入研究，但遗憾的是，迄今为止尚无药物被证明具有临床益处。然而，这些GTP酶也会经历其他可能对其调节很重要的修饰。长期以来，泛素化已被证明可调节众多细胞蛋白的命运，最近很明显，许多GTP酶及其GAP、GeF和GDi会发生泛素化，导致多种命运，如重新定位或降解。在本综述中，我们关注最近的文献，这些文献表明泛素化直接或间接调节小GTP酶，在控制其功能方面发挥着相当重要的作用，并且针对这些修饰可能对疾病治疗很重要。
