Genetics of proteasome diseases.
Genetics of proteasome diseases.
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作者：
Gomes AV
蛋白酶体是一种大型的多亚基复合物，能够降解大多数细胞内蛋白质。蛋白酶体亚基的多态性与心血管疾病、糖尿病、神经系统疾病和癌症有关。蛋白酶体基因 PSMA6 (−8C/G) 的一种多态性与三种不同的疾病相关：2 型糖尿病、心肌梗塞和冠状动脉疾病。一种类型的蛋白酶体，即免疫蛋白酶体，包含可诱导的催化亚基，适合产生用于抗原呈递的肽。最近的研究表明，免疫蛋白酶体催化亚基 PSMB8 的突变和多态性与多种炎症和自身炎症性疾病相关，包括 Nakajo-Nishimura 综合征、CANDLE 综合征和肠道结核分枝杆菌感染。这篇综合综述描述了与人类疾病相关的蛋白酶体基因中与疾病相关的多态性以及这些多态性对蛋白酶体功能的生理调节。鉴于蛋白酶体的大量亚基和在人类生理学中的核心重要性，以及与人类疾病相关的蛋白酶体多态性检测的快速进展，很可能在不久的将来将检测到与疾病相关的蛋白酶体基因中的其他多态性。虽然现在很容易发现与疾病相关的多态性，但挑战在于如何利用这些遗传信息来获得临床益处。
The proteasome is a large, multiple subunit complex that is capable of degrading most intracellular proteins. Polymorphisms in proteasome subunits are associated with cardiovascular diseases, diabetes, neurological diseases, and cancer. One polymorphism in the proteasome gene PSMA6 (−8C/G) is associated with three different diseases: type 2 diabetes, myocardial infarction, and coronary artery disease. One type of proteasome, the immunoproteasome, which contains inducible catalytic subunits, is adapted to generate peptides for antigen presentation. It has recently been shown that mutations and polymorphisms in the immunoproteasome catalytic subunit PSMB8 are associated with several inflammatory and autoinflammatory diseases including Nakajo-Nishimura syndrome, CANDLE syndrome, and intestinal M. tuberculosis infection. This comprehensive review describes the disease-related polymorphisms in proteasome genes associated with human diseases and the physiological modulation of proteasome function by these polymorphisms. Given the large number of subunits and the central importance of the proteasome in human physiology as well as the fast pace of detection of proteasome polymorphisms associated with human diseases, it is likely that other polymorphisms in proteasome genes associated with diseases will be detected in the near future. While disease-associated polymorphisms are now readily discovered, the challenge will be to use this genetic information for clinical benefit.