State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
State Key Laboratory of Biotherapy and Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, And Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
Eur J Med Chem. 2021 Jan 1;209:112917. doi: 10.1016/j.ejmech.2020.112917. Epub 2020 Oct 11.
Atg4, a pivotal macroautophagy/autophagy-related cysteine protein family, which regulate autophagy through either cleaving Atg8 homologs for its further lipidation or delipidating Atg8 homologs from the autophagosome. There are four homologs, Atg4A, Atg4B, Atg4C, and Atg4D. Among them, an increasing amount of evidence indicates that Atg4B possessed superior catalytic efficiency toward the Atg8 substrate, as well as regulates autophagy process and plays a key role in the development of several human cancers. Recently, efforts have been contributed to the exploration of Atg4B inhibitors or activators. In this review, we comprehensively clarify the function of Atg4B in autophagy and cancer biology, as well as the relationship between pharmacological function and structure-activity of small molecule drugs targeting Atg4B. The development of novel drugs targeting Atg4B could be well applied in the clinical practice.
Atg4 是一种关键的巨自噬/自噬相关半胱氨酸蛋白家族，通过切割 Atg8 同源物使其进一步脂质化或从自噬体中去除 Atg8 同源物来调节自噬。有四个同源物，Atg4A、Atg4B、Atg4C 和 Atg4D。其中，越来越多的证据表明 Atg4B 对 Atg8 底物具有更高的催化效率，并且调节自噬过程，在几种人类癌症的发展中起着关键作用。最近，人们致力于探索 Atg4B 的抑制剂或激活剂。在这篇综述中，我们全面阐明了 Atg4B 在自噬和癌症生物学中的作用，以及针对 Atg4B 的小分子药物的药理功能与结构活性之间的关系。靶向 Atg4B 的新型药物的开发可以很好地应用于临床实践。
