E3 泛素连接酶的分子靶向作用——一种癌症治疗方法
Molecular targeting of E3 ligases--a therapeutic approach for cancer.
作者信息
Lakshmanan Manikandan, Bughani Usha, Duraisamy Senthil, Diwan Manish, Dastidar Sunanda, Ray Abhijit
机构信息
Ranbaxy Laboratories Ltd, New Drug Discovery Research, R&D-III, Sector-18, Plot No. 20, Gurgaon-122015, India.
出版信息
Expert Opin Ther Targets. 2008 Jul;12(7):855-70. doi: 10.1517/14728222.12.7.855.
BACKGROUND
The ubiquitin-proteasomal degradation pathway plays a critical role in protein degradation and regulates a wide variety of cellular functions. This highly conserved post-translational modification of proteolytic processes is mainly carried out by substrate-specific E3 ligases. The deregulation of E3 ligases contributes to cancer development and their overexpression is often associated with poor prognosis.
OBJECTIVES
We review the current understanding of E3 ligases, their functional role in cancer pathogenesis, current progress and development of certain ubiquitin E3 ligases as targets for therapeutic intervention.
METHODS
Preclinical and clinical data for E3 ligase inhibitors available in the public domain are discussed.
CONCLUSIONS
With the growing understanding of their role in cancer development and progression, E3 ligases have emerged as potential anticancer targets for therapeutic intervention.
背景
泛素-蛋白酶体降解途径在蛋白质降解中起关键作用，并调节多种细胞功能。这种蛋白水解过程中高度保守的翻译后修饰主要由底物特异性E3连接酶进行。E3连接酶的失调促进癌症发展，其过表达通常与不良预后相关。
目的
我们综述了目前对E3连接酶的认识、它们在癌症发病机制中的功能作用、某些泛素E3连接酶作为治疗干预靶点的研究进展。
方法
讨论了公共领域中可用的E3连接酶抑制剂的临床前和临床数据。
结论
随着对E3连接酶在癌症发展和进展中作用的认识不断加深，E3连接酶已成为治疗干预的潜在抗癌靶点。
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