研究动态
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肿瘤中的微粒体谷胱甘肽转移酶1及其对铁死亡的调控。

Microsomal glutathione transferase 1 in cancer and the regulation of ferroptosis.

发表日期:2023
作者: Jie Zhang, Zhi-Wei Ye, Ralf Morgenstern, Danyelle M Townsend, Kenneth D Tew
来源: PHARMACOLOGY & THERAPEUTICS

摘要:

微粒体谷胱甘肽转移酶1(MGST1)是MAPEG家族的成员之一(与前列腺素和谷胱甘肽代谢有关的膜相关蛋白),根据酶活性、序列基序和结构特性来定义。MGST1是一个由同源三聚体组成的蛋白,可以结合三个谷胱甘肽(GSH)分子,其中一个被修饰为硫醇酸盐,显示三分之一位点的反应性。MGST1具有谷胱甘肽转移酶和过氧化物酶活性,两种活性都依赖于在同一活性位点上稳定GSH硫醇酸盐。MGST1在肝脏中丰富,并且在内质网和线粒体膜中显示出广泛的亚细胞分布,与从反应性电子亲和性中间体和氧化应激保护中起到生理作用相一致。在本综述中,我们特别关注近期在了解MGST1的激活、诱导、广泛的亚细胞分布以及MGST1在凋亡、脂质过氧化、癌症进展和治疗反应方面取得的进展。版权所有 © 2023 Elsevier Inc.发表。
Microsomal glutathione transferase 1 (MGST1) is a member of the MAPEG family (membrane associated proteins in eicosanoid and glutathione metabolism), defined according to enzymatic activities, sequence motifs, and structural properties. MGST1 is a homotrimer which can bind three molecules of glutathione (GSH), with one modified to a thiolate anion displaying one-third-of-sites-reactivity. MGST1 has both glutathione transferase and peroxidase activities. Each is based on stabilizing the GSH thiolate in the same active site. MGST1 is abundant in the liver and displays a broad subcellular distribution with high levels in endoplasmic reticulum and mitochondrial membranes, consistent with a physiological role in protection from reactive electrophilic intermediates and oxidative stress. In this review paper, we particularly focus on recent advances made in understanding MGST1 activation, induction, broad subcellular distribution, and the role of MGST1 in apoptosis, ferroptosis, cancer progression, and therapeutic responses.Copyright © 2023. Published by Elsevier Inc.