泛素特异性半胱氨酸蛋白酶 2a（USP2a）调节 Aurora-A 的稳定性。
Ubiquitin-specific cysteine protease 2a (USP2a) regulates the stability of Aurora-A.
机构信息
Cancer Research Department, Abbott Laboratories, Abbott Park, Illinois 60064, USA.
出版信息
J Biol Chem. 2011 Nov 11;286(45):38960-8. doi: 10.1074/jbc.M111.231498. Epub 2011 Sep 2.
Abstract
The ubiquitin/proteasome pathway plays critical roles in virtually all aspects of cell biology. Enzymes of the ubiquitin pathway add (ligases) or remove (deubiquitinases) ubiquitin tags to or from their target proteins in a selective fashion. USP2a is a member of a subfamily of deubiquitinases, called ubiquitin-specific cysteine proteases (USPs). Although USP2a has been reported to be a bona fide oncogene that regulates the stability of MDM2, MDMX, and FAS, it is likely that there are other unidentified substrates for USP2a. In this study, we show that USP2a mediates mitotic progression by regulating the stability of Aurora-A. Through cell-based screening of a USP siRNA library, we discovered that knockdown of USP2a reduced the protein levels of Aurora-A. USP2a interacts with Aurora-A directly in vitro and in vivo. In addition, Aurora-A is a substrate for USP2a in vitro and in vivo. Our study provides a novel mechanism for the role of USP2a in mediating the stability of Aurora-A.
摘要
泛素/蛋白酶体途径在细胞生物学的几乎所有方面都发挥着关键作用。泛素途径的酶以选择性的方式向或从其靶蛋白添加（连接酶）或去除（去泛素酶）泛素标签。USP2a 是一类称为泛素特异性半胱氨酸蛋白酶 (USPs) 的去泛素酶亚家族的成员。尽管已经报道 USP2a 是调节 MDM2、MDMX 和 FAS 稳定性的真正癌基因，但很可能还有其他未被识别的 USP2a 底物。在这项研究中，我们表明 USP2a 通过调节 Aurora-A 的稳定性来介导有丝分裂进程。通过 USP siRNA 文库的基于细胞的筛选，我们发现 USP2a 的敲低降低了 Aurora-A 的蛋白水平。USP2a 在体外和体内直接与 Aurora-A 相互作用。此外，Aurora-A 是 USP2a 在体外和体内的底物。我们的研究为 USP2a 在介导 Aurora-A 稳定性中的作用提供了一种新的机制。
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