摘要
Skp2经常在许多人类癌症中高度表达,并且在肿瘤发生中起着关键的作用。作为SCFSkp2 E3泛素连接酶复合体中的一种成分,Skp2是负责收集底物蛋白泛素化和连续的通过26S蛋白酶体降解的部分。 因此,Skp2通过下调细胞周期蛋白如肿瘤抑制因子p27促进细胞周期。另外,Skp2抑制p53依赖性的凋亡通过将P300与p53结合,从而扰动p300介导p53的乙酰化和稳定化。综上所述,Skp2功能抑制(或蛋白水解作用或非蛋白水解作用)是一种新兴的有前途的新抗癌策略。在本综述中,我们强调Skp2抑制剂在不同作用机制中的发展。
关键词: 26S蛋白酶体抑制剂;E3连接酶复合体;Skp2抑制剂;Skp2/p27 相互作用;肿瘤发生;泛素蛋白酶体系统。
Current Medicinal Chemistry
Title:Skp2 Inhibitors: Novel Anticancer Strategies
Volume: 23 Issue: 22
Author(s): Yeongju Lee and Hyun-Suk Lim
Affiliation:
关键词: 26S蛋白酶体抑制剂;E3连接酶复合体;Skp2抑制剂;Skp2/p27 相互作用;肿瘤发生;泛素蛋白酶体系统。
摘要: Skp2 is frequently overexpressed in many human cancers and plays a key role in tumorigenesis. As a component of the SCFSkp2 ubiquitin E3 ligase complex, Skp2 is responsible for recruiting substrate proteins for their ubiquitination and subsequent degradation by the 26S proteasome. Thus, Skp2 promotes the cell cycle by down-regulating cell cycle proteins such as the tumor suppressor p27. Alternatively, Skp2 suppresses p53-dependent apoptosis by outcompeting p53 for binding to p300, thereby perturbing p300-mediated p53 acetylation and stabilization. Taken together, inhibition of Skp2 functions (either proteolytic function or non-proteolytic function) is emerging as a promising and novel anti-cancer strategy. In the present review, we highlight the development of Skp2 inhibitors with different mechanisms of action.
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Cite this article as:
Yeongju Lee and Hyun-Suk Lim , Skp2 Inhibitors: Novel Anticancer Strategies, Current Medicinal Chemistry 2016; 23 (22) . https://dx.doi.org/10.2174/0929867323666160510122624
DOI https://dx.doi.org/10.2174/0929867323666160510122624 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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