Li Jie, Zou Jianqiu, Littlejohn Rodney, Liu Jinbao, Su Huabo
Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA, United States.
Protein Modification and Degradation Lab, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.
Front Physiol. 2020 Dec 17;11:612927. doi: 10.3389/fphys.2020.612927. eCollection 2020.
Defects in protein quality control have been increasingly recognized as pathogenic factors in the development of heart failure, a persistent devastating disease lacking efficacious therapies. Ubiquitin and ubiquitin-like proteins, a family of post-translational modifying polypeptides, play important roles in controlling protein quality by maintaining the stability and functional diversity of the proteome. NEDD8 (neural precursor cell expressed, developmentally downregulated 8), a small ubiquitin-like protein, was discovered two decades ago but until recently the biological significance of NEDD8 modifications (neddylation) in the heart has not been appreciated. In this review, we summarize the current knowledge of the biology of neddylation, highlighting several mechanisms by which neddylation regulates the function of its downstream targets, and discuss the expanding roles for neddylation in cardiac physiology and disease, with an emphasis on cardiac protein quality control. Finally, we outline challenges linked to the study of neddylation in health and disease.
蛋白质质量控制缺陷日益被视为心力衰竭发展过程中的致病因素，心力衰竭是一种持续存在且具有毁灭性的疾病，缺乏有效的治疗方法。泛素和类泛素蛋白是一类翻译后修饰多肽，通过维持蛋白质组的稳定性和功能多样性，在控制蛋白质质量方面发挥重要作用。NEDD8（神经前体细胞表达，发育下调8）是一种小的类泛素蛋白，二十年前被发现，但直到最近，NEDD8修饰（NEDD化）在心脏中的生物学意义才受到重视。在这篇综述中，我们总结了目前关于NEDD化生物学的知识，强调了NEDD化调节其下游靶点功能的几种机制，并讨论了NEDD化在心脏生理学和疾病中不断扩展的作用，重点是心脏蛋白质质量控制。最后，我们概述了与健康和疾病中NEDD化研究相关的挑战。
