Ludwig Institute for Cancer Research, 1200 Brussels, Belgium.
De Duve Institute, Université Catholique de Louvain, 1200 Brussels, Belgium.
Cells. 2022 Jan 26;11(3):421. doi: 10.3390/cells11030421.
Four proteasome subtypes are commonly present in mammalian tissues: standard proteasomes, which contain the standard catalytic subunits β1, β2 and β5; immunoproteasomes containing the immuno-subunits β1i, β2i and β5i; and two intermediate proteasomes, containing a mix of standard and immuno-subunits. Recent studies revealed the expression of two tissue-specific proteasome subtypes in cortical thymic epithelial cells and in testes: thymoproteasomes and spermatoproteasomes. In this review, we describe the mechanisms that enable the ATP- and ubiquitin-dependent as well as the ATP- and ubiquitin-independent degradation of proteins by the proteasome. We focus on understanding the role of the different proteasome subtypes in maintaining protein homeostasis in normal physiological conditions through the ATP- and ubiquitin-dependent degradation of proteins. Additionally, we discuss the role of each proteasome subtype in the ATP- and ubiquitin-independent degradation of disordered proteins. We also discuss the role of the proteasome in the generation of peptides presented by MHC class I molecules and the implication of having different proteasome subtypes for the peptide repertoire presented at the cell surface. Finally, we discuss the role of the immunoproteasome in immune cells and its modulation as a potential therapy for autoimmune diseases.
标准蛋白酶体，包含标准催化亚基β1、β2 和β5；免疫蛋白酶体，包含免疫亚基β1i、β2i 和β5i；以及两种中间蛋白酶体，包含标准和免疫亚基的混合物。最近的研究揭示了皮质胸腺上皮细胞和睾丸中两种组织特异性蛋白酶体亚型的表达：胸腺蛋白酶体和精子蛋白酶体。在这篇综述中，我们描述了蛋白酶体通过 ATP 和泛素依赖性以及 ATP 和泛素非依赖性降解蛋白质的机制。我们专注于理解不同蛋白酶体亚型在通过 ATP 和泛素依赖性降解蛋白质来维持正常生理条件下的蛋白质平衡中的作用。此外，我们讨论了每种蛋白酶体亚型在无规蛋白质的 ATP 和泛素非依赖性降解中的作用。我们还讨论了蛋白酶体在 MHC Ⅰ类分子呈递肽中的作用以及存在不同蛋白酶体亚型对细胞表面呈递肽谱的影响。最后，我们讨论了免疫蛋白酶体在免疫细胞中的作用及其作为自身免疫性疾病潜在治疗方法的调节作用。
