Jafari Hedieh, Hussain Shahid, Campbell Moray J
Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210, USA.
Department of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
Cancers (Basel). 2022 May 13;14(10):2402. doi: 10.3390/cancers14102402.
Nuclear receptors (NRs) function collectively as a transcriptional signaling network that mediates gene regulatory actions to either maintain cellular homeostasis in response to hormonal, dietary and other environmental factors, or act as orphan receptors with no known ligand. NR complexes are large and interact with multiple protein partners, collectively termed coregulators. Coregulators are essential for regulating NR activity and can dictate whether a target gene is activated or repressed by a variety of mechanisms including the regulation of chromatin accessibility. Altered expression of coregulators contributes to a variety of hormone-dependent cancers including breast and prostate cancers. Therefore, understanding the mechanisms by which coregulators interact with and modulate the activity of NRs provides opportunities to develop better prognostic and diagnostic approaches, as well as novel therapeutic targets. This review aims to gather and summarize recent studies, techniques and bioinformatics methods used to identify distorted NR coregulator interactions that contribute as cancer drivers in hormone-dependent cancers.
核受体(NRs)共同构成一个转录信号网络,介导基因调控作用,以响应激素、饮食和其他环境因素维持细胞内稳态,或作为没有已知配体的孤儿受体发挥作用。核受体复合物很大,且与多个蛋白质伴侣相互作用,这些蛋白质伴侣统称为共调节因子。共调节因子对于调节核受体活性至关重要,并且可以通过多种机制(包括染色质可及性的调节)来决定靶基因是被激活还是被抑制。共调节因子的表达改变会导致包括乳腺癌和前列腺癌在内的多种激素依赖性癌症。因此,了解共调节因子与核受体相互作用并调节其活性的机制,为开发更好的预后和诊断方法以及新的治疗靶点提供了机会。本综述旨在收集和总结最近用于识别扭曲的核受体共调节因子相互作用的研究、技术和生物信息学方法,这些相互作用在激素依赖性癌症中作为癌症驱动因素发挥作用。