针对癌症中F-box蛋白的小分子疗法。
Small molecule therapeutics targeting F-box proteins in cancer.
作者信息
Liu Yuan, Mallampalli Rama K
机构信息
Department of Medicine, The Acute Lung Injury, Center of Excellence, University of Pittsburgh, Pittsburgh, PA 15213, United States.
Department of Medicine, The Acute Lung Injury, Center of Excellence, University of Pittsburgh, Pittsburgh, PA 15213, United States; Medical Specialty Service Line, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA 15240, United States.
出版信息
Semin Cancer Biol. 2016 Feb;36:105-19. doi: 10.1016/j.semcancer.2015.09.014. Epub 2015 Sep 30.
Abstract
The ubiquitin proteasome system (UPS) plays vital roles in maintaining protein equilibrium mainly through proteolytic degradation of targeted substrates. The archetypical SCF ubiquitin E3 ligase complex contains a substrate recognition subunit F-box protein that recruits substrates to the catalytic ligase core for its polyubiquitylation and subsequent proteasomal degradation. Several well-characterized F-box proteins have been demonstrated that are tightly linked to neoplasia. There is mounting information characterizing F-box protein-substrate interactions with the rationale to develop unique therapeutics for cancer treatment. Here we review that how F-box proteins function in cancer and summarize potential small molecule inhibitors for cancer therapy.
摘要
泛素蛋白酶体系统（UPS）在维持蛋白质平衡中起着至关重要的作用，主要通过对靶向底物的蛋白水解降解来实现。典型的SCF泛素E3连接酶复合物包含一个底物识别亚基F-box蛋白，该蛋白将底物招募到催化连接酶核心，以进行其多聚泛素化及随后的蛋白酶体降解。已证实几种特征明确的F-box蛋白与肿瘤形成密切相关。越来越多的信息描述了F-box蛋白与底物的相互作用，其目的是开发用于癌症治疗的独特疗法。在此，我们综述F-box蛋白在癌症中的作用方式，并总结用于癌症治疗的潜在小分子抑制剂。
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