HECT 泛素蛋白连接酶 E6AP 和 HERC2 的物理和功能相互作用。
Physical and functional interaction of the HECT ubiquitin-protein ligases E6AP and HERC2.
机构信息
Department of Biology and Konstanz Research School Chemical Biology, University of Konstanz, Konstanz, Germany.
出版信息
J Biol Chem. 2011 Jun 3;286(22):19410-6. doi: 10.1074/jbc.M110.205211. Epub 2011 Apr 14.
Abstract
Deregulation of the ubiquitin-protein ligase E6AP contributes to the development of the Angelman syndrome and to cervical carcinogenesis suggesting that the activity of E6AP needs to be under tight control. However, how E6AP activity is regulated at the post-translational level under non-pathologic conditions is poorly understood. In this study, we report that the giant protein HERC2, which is like E6AP a member of the HECT family of ubiquitin-protein ligases, binds to E6AP. The interaction is mediated by the RCC1-like domain 2 of HERC2 and a region spanning amino acid residues 150-200 of E6AP. Furthermore, we provide evidence that HERC2 stimulates the ubiquitin-protein ligase activity of E6AP in vitro and within cells and that this stimulatory effect does not depend on the ubiquitin-protein ligase activity of HERC2. Thus, the data obtained indicate that HERC2 acts as a regulator of E6AP.
摘要
泛素连接酶 E6AP 的去调控作用导致了 Angelman 综合征和宫颈癌的发生，这表明 E6AP 的活性需要受到严格的控制。然而，在非病理条件下，E6AP 的活性如何在翻译后水平上受到调节还知之甚少。在这项研究中，我们报告了巨型蛋白 HERC2 与 E6AP 结合，HERC2 像 E6AP 一样，是泛素连接酶家族的 HECT 家族的一员。这种相互作用是由 HERC2 的 RCC1 样结构域 2 和 E6AP 的氨基酸残基 150-200 之间的区域介导的。此外，我们提供的证据表明，HERC2 在体外和细胞内刺激 E6AP 的泛素连接酶活性，并且这种刺激作用不依赖于 HERC2 的泛素连接酶活性。因此，获得的数据表明 HERC2 是 E6AP 的调节剂。
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