College of Chemistry and Chemical Engineering, Xi'an University of Science and Technology, Xi'an, Shanxi, China 710054.
Gustaf H. Carlson School of Chemistry and Biochemistry, Clark University, 950 Main St., Worcester, MA 01610, USA.
J Cell Sci. 2020 Apr 7;133(7):jcs228072. doi: 10.1242/jcs.228072.
Homologous to E6AP C-terminus (HECT) E3 ubiquitin ligases play a critical role in various cellular pathways, including but not limited to protein trafficking, subcellular localization, innate immune response, viral infections, DNA damage responses and apoptosis. To date, 28 HECT E3 ubiquitin ligases have been identified in humans, and recent studies have begun to reveal how these enzymes control various cellular pathways by catalyzing the post-translational attachment of ubiquitin to their respective substrates. New studies have identified substrates and/or interactors with different members of the HECT E3 ubiquitin ligase family, particularly for E6AP and members of the neuronal precursor cell-expressed developmentally downregulated 4 (NEDD4) family. However, there still remains many unanswered questions about the specific roles that each of the HECT E3 ubiquitin ligases have in maintaining cellular homeostasis. The present Review discusses our current understanding on the biological roles of the HECT E3 ubiquitin ligases in the cell and how they contribute to disease development. Expanded investigations on the molecular basis for how and why the HECT E3 ubiquitin ligases recognize and regulate their intracellular substrates will help to clarify the biochemical mechanisms employed by these important enzymes in ubiquitin biology.
同源于 E6AP C 端（HECT）的 E3 泛素连接酶在多种细胞途径中发挥着关键作用，包括但不限于蛋白质运输、亚细胞定位、先天免疫反应、病毒感染、DNA 损伤反应和细胞凋亡。迄今为止，人类已鉴定出 28 种 HECT E3 泛素连接酶，最近的研究开始揭示这些酶如何通过催化泛素对其各自底物的翻译后附着来控制各种细胞途径。新的研究已经确定了具有不同 HECT E3 泛素连接酶家族成员（特别是 E6AP 和神经元前体细胞表达的发育下调 4（NEDD4）家族成员）的底物和/或相互作用物。然而，对于每个 HECT E3 泛素连接酶在维持细胞内稳态中的具体作用，仍有许多悬而未决的问题。本综述讨论了我们目前对 HECT E3 泛素连接酶在细胞中的生物学作用的理解，以及它们如何促进疾病的发展。对 HECT E3 泛素连接酶如何以及为何识别和调节其细胞内底物的分子基础的扩展研究将有助于阐明这些重要酶在泛素生物学中采用的生化机制。
