Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China; These authors contributed equally to this work.
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA.
Trends Endocrinol Metab. 2017 Nov;28(11):818-830. doi: 10.1016/j.tem.2017.09.001. Epub 2017 Sep 28.
p62, a protein capable of binding both ubiquitin and autophagy substrates, is well established as a key regulator in cancer and neurodegenerative diseases. Recently, there has been accumulating evidence that p62 is also a pivotal regulator in metabolic diseases, such as obesity, T2DM, NAFLD, metabolic bone disease, gout and thyroid disease. This review summarizes the emerging role of p62 on these diseases by considering its functional domains, phenotypes in genetically modified animals, clinically observed alterations, and its effects on downstream metabolic signaling pathways. At the same time, we highlight the need to explore the roles played by p62 in the gastrointestinal environment and immune system, and the extent to which its elevated expression may confer protection against metabolic disorders.
p62 是一种能够结合泛素和自噬底物的蛋白质，它是癌症和神经退行性疾病的关键调节因子已得到充分证实。最近，越来越多的证据表明，p62 也是肥胖症、T2DM、NAFLD、代谢性骨病、痛风和甲状腺疾病等代谢性疾病的关键调节因子。通过考虑其功能结构域、基因修饰动物的表型、临床观察到的变化以及对下游代谢信号通路的影响，本综述总结了 p62 在这些疾病中的新作用。同时，我们强调需要探索 p62 在胃肠道环境和免疫系统中的作用，以及其高表达可能在多大程度上对代谢紊乱提供保护。
