Acute Lung Injury Center of Excellence, Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pennsylvania, USA.
Am J Respir Crit Care Med. 2013 Sep 1;188(5):530-7. doi: 10.1164/rccm.201304-0754PP.
Derangements in normal cellular homeostasis at the protein level can cause or be the consequence of initiation and progression of pulmonary diseases related to genotype, infection, injury, smoking, toxin exposure, or neoplasm. We discuss one of the fundamental mechanisms of protein homeostasis, the ubiquitin proteasome system (UPS), as it relates to lung disease. The UPS effects selective degradation of ubiquitinated target proteins via ubiquitin ligase activity. Important pathobiological mechanisms relating to the UPS and lung disease have been the focus of research, with inappropriate cellular proteolysis now a validated therapeutic target. We review the contributions of this system in various lung diseases, and discuss the exciting area of UPS-targeting drug development for pulmonary disease.
蛋白质水平正常细胞内稳态的紊乱可导致与基因型、感染、损伤、吸烟、毒素暴露或肿瘤相关的肺部疾病的发生和进展，或者是其结果。我们讨论了蛋白质内稳态的基本机制之一，即泛素蛋白酶体系统 (UPS)，因为它与肺部疾病有关。UPS 通过泛素连接酶活性对泛素化靶蛋白进行选择性降解。UPS 与肺部疾病相关的重要病理生物学机制一直是研究的重点，现在不适当的细胞内蛋白水解已成为一个经过验证的治疗靶点。我们综述了该系统在各种肺部疾病中的作用，并讨论了 UPS 靶向药物开发这一肺部疾病治疗的令人兴奋的领域。
