UBC James Hogg iCAPTURE Centre, Institute for Heart and Lung Health, St. Paul's Hospital, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
Front Biosci (Landmark Ed). 2012 Jan 1;17(5):1904-16. doi: 10.2741/4027.
The biological importance of the ubiquitin-proteasome system in the control of myriad cellular processes has been well-recognized; however, the pathophysiological significance of the immunoproteasome, the inducible form of the proteasome, has not been well-comprehended until lately. The primary function of the immunoproteasome was originally believed to improve MHC-I antigen presentation. It now becomes evident that the immunoproteasome possesses broader biological functions. It regulates proinflammatory cytokine production, and T cell differentiation and proliferation. Alongside immune functions, the immunoproteasome has been demonstrated to relieve oxidative stress by the efficient turnover of oxidatively-damaged proteins and by allaying the formation of harmful protein aggregates. Furthermore, it has been implicated to regulate tumor cell growth and control muscle mass. Finally, the immunoproteasome has recently drawn considerable attention as a potential novel therapeutic target for cancer and autoimmune disease. This review will give an overview of the structure and function of the immunoproteasome, highlight its functional diversity in both immune and non-immune responses, and discuss the relationship between the dysregulation of the immunoproteasome and the development of several human diseases.
泛素-蛋白酶体系统在控制众多细胞过程中的生物学重要性已得到充分认识；然而，直到最近，免疫蛋白酶体（蛋白酶体的诱导形式）的病理生理学意义才被充分理解。免疫蛋白酶体的主要功能最初被认为是改善 MHC-I 抗原呈递。现在很明显，免疫蛋白酶体具有更广泛的生物学功能。它调节前炎性细胞因子的产生以及 T 细胞的分化和增殖。除了免疫功能外，免疫蛋白酶体还通过有效清除氧化损伤蛋白和减轻有害蛋白聚集体的形成来缓解氧化应激。此外，它还被认为可以调节肿瘤细胞的生长和控制肌肉质量。最后，免疫蛋白酶体最近作为癌症和自身免疫性疾病的潜在新治疗靶点引起了广泛关注。本文将概述免疫蛋白酶体的结构和功能，强调其在免疫和非免疫反应中的功能多样性，并讨论免疫蛋白酶体失调与几种人类疾病发展之间的关系。
