Department of Pathology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
Pathol Int. 2021 Jun;71(6):371-382. doi: 10.1111/pin.13088. Epub 2021 Mar 3.
The proteasome is a multisubunit protease that degrades intracellular proteins into small peptides. Besides playing a pivotal role in many cellular processes indispensable for survival, it is involved in the production of peptides presented by major histocompatibility complex class I molecules. In addition to the standard proteasome shared in all eukaryotes, jawed vertebrates have two specialized forms of proteasome known as immunoproteasomes and thymoproteasomes. The immunoproteasome, which contains cytokine-inducible catalytic subunits with distinct cleavage specificities, produces peptides presented by class I molecules more efficiently than the standard proteasome. The thymoproteasome, which contains a unique catalytic subunit β5t, is a tissue-specific proteasome expressed exclusively in cortical thymic epithelial cells. It plays a critical role in CD8 cytotoxic T cell development via positive selection. This review provides a brief overview on the structure and function of these specialized forms of proteasome and their involvement in human disease.
蛋白酶体是一种多亚基蛋白酶，可将细胞内蛋白质降解为小肽。除了在许多对生存至关重要的细胞过程中发挥关键作用外，它还参与了主要组织相容性复合体 I 类分子呈递的肽的产生。除了所有真核生物共有的标准蛋白酶体外，有颌脊椎动物还有两种特殊形式的蛋白酶体，称为免疫蛋白酶体和胸腺蛋白酶体。免疫蛋白酶体含有具有独特切割特异性的细胞因子诱导的催化亚基，比标准蛋白酶体更有效地产生 I 类分子呈递的肽。胸腺蛋白酶体含有独特的催化亚基 β5t，是一种组织特异性蛋白酶体，仅在皮质胸腺上皮细胞中表达。它通过阳性选择在 CD8 细胞毒性 T 细胞发育中发挥关键作用。本文简要概述了这些特殊形式的蛋白酶体的结构和功能及其在人类疾病中的作用。
