Department of Digestive Diseases, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, 161 Shaoshan Road, Changsha 410000, China.
Biomolecules. 2024 May 13;14(5):577. doi: 10.3390/biom14050577.
Protein ubiquitination is an enzymatic cascade reaction and serves as an important protein post-translational modification (PTM) that is involved in the vast majority of cellular life activities. The key enzyme in the ubiquitination process is E3 ubiquitin ligase (E3), which catalyzes the binding of ubiquitin (Ub) to the protein substrate and influences substrate specificity. In recent years, the relationship between the subfamily of neuron-expressed developmental downregulation 4 (NEDD4), which belongs to the E3 ligase system, and digestive diseases has drawn widespread attention. Numerous studies have shown that NEDD4 and NEDD4L of the NEDD4 family can regulate the digestive function, as well as a series of related physiological and pathological processes, by controlling the subsequent degradation of proteins such as PTEN, c-Myc, and P21, along with substrate ubiquitination. In this article, we reviewed the appropriate functions of NEDD4 and NEDD4L in digestive diseases including cell proliferation, invasion, metastasis, chemotherapeutic drug resistance, and multiple signaling pathways, based on the currently available research evidence for the purpose of providing new ideas for the prevention and treatment of digestive diseases.
蛋白质泛素化是一种酶级联反应，作为一种重要的蛋白质翻译后修饰（PTM），参与了绝大多数细胞生命活动。泛素化过程中的关键酶是 E3 泛素连接酶（E3），它催化泛素（Ub）与蛋白质底物的结合，并影响底物特异性。近年来，属于 E3 连接酶系统的神经元表达发育下调 4 （NEDD4）亚家族与消化疾病之间的关系引起了广泛关注。大量研究表明，NEDD4 和 NEDD4L 家族可以通过控制 PTEN、c-Myc 和 P21 等蛋白的后续降解以及底物泛素化，调节消化功能以及一系列相关的生理和病理过程。本文根据目前的研究证据，综述了 NEDD4 和 NEDD4L 在包括细胞增殖、侵袭、转移、化疗药物耐药性和多种信号通路在内的消化疾病中的适当功能，以期为消化疾病的防治提供新的思路。
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