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E3 Ubiquitin ligase NEDD4 family‑regulatory network in cardiovascular disease
International Journal of Biological Sciences ( IF 8.2 ) Pub Date : 2020-8-21 , DOI: 10.7150/ijbs.48437
Ying Zhang 1 , Hao Qian 1 , Boquan Wu 1 , Shilong You 1 , Shaojun Wu 1 , Saien Lu 1 , Pingyuan Wang 2 , Liu Cao 3 , Naijin Zhang 1 , Yingxian Sun 1
Affiliation  

Protein ubiquitination represents a critical modification occurring after translation. E3 ligase catalyzes the covalent binding of ubiquitin to the protein substrate, which could be degraded. Ubiquitination as an important protein post-translational modification is closely related to cardiovascular disease. The NEDD4 family, belonging to HECT class of E3 ubiquitin ligases can recognize different substrate proteins, including PTEN, ENaC, Nav1.5, SMAD2, PARP1, Septin4, ALK1, SERCA2a, TGFβR3 and so on, via the WW domain to catalyze ubiquitination, thus participating in multiple cardiovascular-related disease such as hypertension, arrhythmia, myocardial infarction, heart failure, cardiotoxicity, cardiac hypertrophy, myocardial fibrosis, cardiac remodeling, atherosclerosis, pulmonary hypertension and heart valve disease. However, there is currently no review comprehensively clarifying the important role of NEDD4 family proteins in the cardiovascular system. Therefore, the present review summarized recent studies about NEDD4 family members in cardiovascular disease, providing novel insights into the prevention and treatment of cardiovascular disease. In addition, assessing transgenic animals and performing gene silencing would further identify the ubiquitination targets of NEDD4. NEDD4 quantification in clinical samples would also constitute an important method for determining NEDD4 significance in cardiovascular disease.

中文翻译:

E3 泛素连接酶 NEDD4 家族调控网络在心血管疾病中的作用

蛋白质泛素化代表翻译后发生的关键修饰。E3 连接酶催化泛素与可能被降解的蛋白质底物的共价结合。泛素化作为一种​​重要的蛋白质翻译后修饰与心血管疾病密切相关。NEDD4家族属于HECT类E3泛素连接酶,可以识别不同的底物蛋白,包括PTEN、ENaC、Nav1.5、SMAD2、PARP1、Septin4、ALK1、SERCA2a、TGFβR3等,通过WW结构域催化泛素化,从而参与高血压、心律失常、心肌梗塞、心力衰竭、心脏毒性、心脏肥大、心肌纤维化、心脏重构、动脉粥样硬化、肺动脉高压和心脏瓣膜病等多种心血管相关疾病。然而,目前还没有综述全面阐明 NEDD4 家族蛋白在心血管系统中的重要作用。因此,本综述总结了近期关于 NEDD4 家族成员在心血管疾病中的研究,为心血管疾病的预防和治疗提供了新的见解。此外,评估转基因动物和进行基因沉默将进一步确定 NEDD4 的泛素化目标。临床样本中的 NEDD4 定量也将构成确定 NEDD4 在心血管疾病中的重要性的重要方法。为心血管疾病的预防和治疗提供新的见解。此外,评估转基因动物和进行基因沉默将进一步确定 NEDD4 的泛素化目标。临床样本中的 NEDD4 定量也将构成确定 NEDD4 在心血管疾病中的重要性的重要方法。为心血管疾病的预防和治疗提供新的见解。此外,评估转基因动物和进行基因沉默将进一步确定 NEDD4 的泛素化目标。临床样本中的 NEDD4 定量也将构成确定 NEDD4 在心血管疾病中的重要性的重要方法。
更新日期:2020-08-27
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