Li Mohan, Sun Guozhe, Wang Pengbo, Wang Wenbin, Cao Kexin, Song Chunyu, Sun Yingxian, Zhang Ying, Zhang Naijin
Department of Cardiology, First Hospital of China Medical University, Shenyang, Liaoning, China.
Institute of Health Sciences, China Medical University, Shenyang, Liaoning, China.
Cell Death Discov. 2022 Apr 16;8(1):206. doi: 10.1038/s41420-022-01017-1.
Post-translational modifications (PTMs) are a covalent processing process of proteins after translation. Proteins are capable of playing their roles only after being modified, so as to maintain the normal physiological function of cells. As a key modification of protein post-translational modification, ubiquitination is an essential element, which forms an enzyme-linked reaction through ubiquitin-activating enzyme, ubiquitin binding enzyme, and ubiquitin ligase, aiming to regulate the expression level and function of cellular proteins. Nedd4 family is the largest group of ubiquitin ligases, including 9 members, such as Nedd4-1, Nedd4L (Nedd4-2), WWP1, WWP2, ITCH, etc. They could bind to substrate proteins through their WW domain and play a dominant role in the ubiquitination process, and then participate in various pathophysiological processes of cardiovascular diseases (such as hypertension, myocardial hypertrophy, heart failure, etc.). At present, the role of Nedd4L in the cardiovascular field is not fully understood. This review aims to summarize the progress and mechanism of Nedd4L in cardiovascular diseases, and provide potential perspective for the clinical treatment or prevention of related cardiovascular diseases by targeting Nedd4L.
翻译后修饰（PTMs）是蛋白质翻译后的一种共价加工过程。蛋白质只有在经过修饰后才能发挥其作用，从而维持细胞的正常生理功能。作为蛋白质翻译后修饰的一种关键修饰，泛素化是一个重要元素，它通过泛素激活酶、泛素结合酶和泛素连接酶形成酶联反应，旨在调节细胞蛋白质的表达水平和功能。Nedd4家族是最大的泛素连接酶组，包括9个成员，如Nedd4-1、Nedd4L（Nedd4-2）、WWP1、WWP2、ITCH等。它们可以通过其WW结构域与底物蛋白结合，并在泛素化过程中起主导作用，进而参与心血管疾病的各种病理生理过程（如高血压、心肌肥大、心力衰竭等）。目前，Nedd4L在心血管领域的作用尚未完全明确。本综述旨在总结Nedd4L在心血管疾病中的研究进展及机制，并为通过靶向Nedd4L对相关心血管疾病进行临床治疗或预防提供潜在的研究方向。
