Morozov Alexey V, Karpov Vadim L
Laboratory of Regulation of Intracellular Proteolysis, W.A. Engelhardt Institute of Molecular Biology RAS, Moscow, Russia.
Front Oncol. 2019 Aug 13;9:761. doi: 10.3389/fonc.2019.00761. eCollection 2019.
The life of every organism is dependent on the fine-tuned mechanisms of protein synthesis and breakdown. The degradation of most intracellular proteins is performed by the ubiquitin proteasome system (UPS). Proteasomes are central elements of the UPS and represent large multisubunit protein complexes directly responsible for the protein degradation. Accumulating data indicate that there is an intriguing diversity of cellular proteasomes. Different proteasome forms, containing different subunits and attached regulators have been described. In addition, proteasomes specific for a particular tissue were identified. Cancer cells are highly dependent on the proper functioning of the UPS in general, and proteasomes in particular. At the same time, the information regarding the role of different proteasome forms in cancer is limited. This review describes the functional and structural heterogeneity of proteasomes, their association with cancer as well as several established and novel proteasome-directed therapeutic strategies.
每个生物体的生命都依赖于蛋白质合成与分解的精细调节机制。大多数细胞内蛋白质的降解是由泛素蛋白酶体系统（UPS）完成的。蛋白酶体是UPS的核心组成部分，是直接负责蛋白质降解的大型多亚基蛋白质复合物。越来越多的数据表明，细胞蛋白酶体具有引人入胜的多样性。已经描述了含有不同亚基和附着调节因子的不同蛋白酶体形式。此外，还鉴定出了特定组织特有的蛋白酶体。一般来说，癌细胞高度依赖于UPS的正常功能，尤其是蛋白酶体。与此同时，关于不同形式蛋白酶体在癌症中的作用的信息有限。本综述描述了蛋白酶体的功能和结构异质性、它们与癌症的关联以及几种已确立的和新颖的蛋白酶体导向治疗策略。
