Schwartz Alan L, Ciechanover Aaron
Department of Pediatrics, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, Missouri 63110, USA.
Annu Rev Pharmacol Toxicol. 2009;49:73-96. doi: 10.1146/annurev.pharmtox.051208.165340.
Cellular proteins are in a dynamic state maintained by synthesis and degradation. The ubiquitin proteolytic pathway is responsible for the degradation of the bulk of cellular proteins including short-lived, regulatory, and misfolded/denatured proteins. Ubiquitin-mediated proteolysis involves covalent attachment of multiple ubiquitin molecules to the protein substrate and degradation of the targeted protein by the 26S proteasome. Recent understanding of the molecular mechanisms involved provides a framework to understand a wide variety of human pathophysiological states as well as therapeutic interventions. This review focuses on the response to hypoxia, inflammatory diseases, neurodegenerative diseases, and muscle-wasting disorders, as well as human papillomaviruses, cervical cancer and other malignancies.
细胞蛋白质处于由合成和降解维持的动态状态。泛素蛋白水解途径负责降解大部分细胞蛋白质，包括短命的、调节性的以及错误折叠/变性的蛋白质。泛素介导的蛋白水解涉及多个泛素分子与蛋白质底物的共价连接以及26S蛋白酶体对靶向蛋白质的降解。对所涉及分子机制的最新理解为理解多种人类病理生理状态以及治疗干预提供了一个框架。本综述重点关注对缺氧、炎症性疾病、神经退行性疾病和肌肉萎缩性疾病的反应，以及人乳头瘤病毒、宫颈癌和其他恶性肿瘤。
