Chan Chia-Hsin, Lee Szu-Wei, Wang Jing, Lin Hui-Kuan
1Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
ScientificWorldJournal. 2010 Jun 1;10:1001-15. doi: 10.1100/tsw.2010.89.
The regulation of cell cycle entry is critical for cell proliferation and tumorigenesis. One of the key players regulating cell cycle progression is the F-box protein Skp2. Skp2 forms a SCF complex with Skp1, Cul-1, and Rbx1 to constitute E3 ligase through its F-box domain. Skp2 protein levels are regulated during the cell cycle, and recent studies reveal that Skp2 stability, subcellular localization, and activity are regulated by its phosphorylation. Overexpression of Skp2 is associated with a variety of human cancers, indicating that Skp2 may contribute to the development of human cancers. The notion is supported by various genetic mouse models that demonstrate an oncogenic activity of Skp2 and its requirement in cancer progression, suggesting that Skp2 may be a novel and attractive therapeutic target for cancers.
细胞周期进入的调控对于细胞增殖和肿瘤发生至关重要。调节细胞周期进程的关键因子之一是F-box蛋白Skp2。Skp2通过其F-box结构域与Skp1、Cul-1和Rbx1形成SCF复合物，构成E3连接酶。Skp2蛋白水平在细胞周期中受到调控，最近的研究表明，Skp2的稳定性、亚细胞定位和活性受其磷酸化调节。Skp2的过表达与多种人类癌症相关，表明Skp2可能促进人类癌症的发展。各种基因小鼠模型支持了这一观点，这些模型证明了Skp2的致癌活性及其在癌症进展中的必要性，提示Skp2可能是一种新型且有吸引力的癌症治疗靶点。
