Identification of cytochrome c oxidase subunit 6A1 as a suppressor of Bax-induced cell death by yeast-based functional screening
Identification of cytochrome c oxidase subunit 6A1 as a suppressor of Bax-induced cell death by yeast-based functional screening
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DOI：
10.1016/j.bbrc.2008.05.178
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发表时间：
2008-08-15
影响因子：
3.1
通讯作者：
Seo, Han Geuk
中科院分区：
文献类型：
--
作者：
Eun, So Young;Woo, Im Sun;Seo, Han Geuk
通过对哺乳动物 cDNA 文库进行基于酵母的功能筛选，人细胞色素 C 氧化酶亚基 VIa 多肽 1 (COX6A1) 被鉴定为 Bcl-2 相关 X 蛋白 (Bax) 介导的细胞死亡的新型抑制剂。 COX6A1 的过表达分别显着抑制 Bax 和 N-(4-羟苯基)视黄酰胺 (4-HPR) 诱导的酵母细胞和人胶质母细胞瘤来源的 U373MG 细胞的细胞凋亡。在表达 COX6A1 的酵母和 U373MG 细胞中，响应 Bax 或 4-HPR 的活性氧 (ROS) 的产生受到抑制，表明 COX6A1 对 ROS 诱导的细胞损伤发挥保护作用。在稳定表达 COX6A1 的 U373MG 细胞中，4-HPR 诱导的线粒体 Bax 易位、线粒体细胞色素 c 释放和 caspase-3 激活显着减弱。我们的结果表明，基于酵母的人类基因功能筛选酵母中 Bax 敏感性抑制剂，鉴定出一种蛋白质，该蛋白质不仅可以抑制酵母中 Bax 的毒性，而且在保护哺乳动物细胞免受 4-HPR 诱导的细胞凋亡中具有潜在作用。 (C) 2008 Elsevier Inc. 保留所有权利。
Human cytochrome c oxidase subunit VIa polypeptide 1 (COX6A1) was identified as a novel Suppressor of Bcl-2-associated X protein (Bax)-mediated cell death using yeast-based functional screening of a mammalian cDNA library. The overexpression of COX6A1 significantly suppressed Bax- and N-(4-hydroxyphenyl)retinamide (4-HPR)-induced apoptosis in yeast and human glioblastoma-derived U373MG cells, respectively. The generation of reactive oxygen species (ROS) in response to Bax or 4-HPR was inhibited in yeast and U373MG cells that expressed COX6A1, indicating that COX6A1 exerts a protective effect against ROS-induced cell damage. 4-HPR-induced mitochondrial translocation of Bax, release of mitochondrial cytochrome c, and activation of caspase-3 were markedly attenuated in U373MG cells that stably expressed COX6A1. Our results demonstrate that yeast-based functional screening of human genes for inhibitors of Bax-sensitivity in yeast identified a protein that not only suppresses the toxicity of Bax in yeast, but also has a potential role in protecting mammalian cells from 4-HPR-induced apoptosis. (C) 2008 Elsevier Inc. All rights reserved.