Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 5 Kooperativny Street, 634009 Tomsk, Russia.
Koltzov Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilov Street, 119334 Moscow, Russia.
Biomolecules. 2020 Mar 26;10(4):500. doi: 10.3390/biom10040500.
This review provides information on the structure of estrogen receptors (ERs), their localization and functions in mammalian cells. Additionally, the structure of proteasomes and mechanisms of protein ubiquitination and cleavage are described. According to the modern concept, the ubiquitin proteasome system (UPS) is involved in the regulation of the activity of ERs in several ways. First, UPS performs the ubiquitination of ERs with a change in their functional activity. Second, UPS degrades ERs and their transcriptional regulators. Third, UPS affects the expression of ER genes. In addition, the opportunity of the regulation of proteasome functioning by ERs-in particular, the expression of immune proteasomes-is discussed. Understanding the complex mechanisms underlying the regulation of ERs and proteasomes has great prospects for the development of new therapeutic agents that can make a significant contribution to the treatment of diseases associated with the impaired function of these biomolecules.
这篇综述提供了关于雌激素受体(ERs)的结构、它们在哺乳动物细胞中的定位和功能的信息。此外,还描述了蛋白酶体的结构和蛋白质泛素化和切割的机制。根据现代概念,泛素蛋白酶体系统(UPS)通过多种方式参与 ERs 活性的调节。首先,UPS 对 ERs 进行泛素化修饰,从而改变其功能活性。其次,UPS 降解 ERs 及其转录调节剂。第三,UPS 影响 ER 基因的表达。此外,还讨论了 ERs 调节蛋白酶体功能的机会——特别是免疫蛋白酶体的表达。深入了解 ERs 和蛋白酶体调节的复杂机制,为开发新的治疗药物提供了广阔的前景,这些药物可能会对治疗与这些生物分子功能障碍相关的疾病做出重大贡献。