Identification of cytochrome c oxidase subunit 6A1 as a suppressor of Bax-induced cell death by yeast-based functional screening
- Authors
- Eun, So Young; Woo, Im Sun; Jang, Han-Su; Jin, Hana; Kim, Min Young; Kim, Hye Jung; Lee, Jae Heun; Chang, Ki Churl; Kim, Jin-Hoi; Seo, Han Geuk
- Issue Date
- 15-Aug-2008
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Keywords
- 4-HPR; COX6A1; ROS; apoptosis; Bax; JNK
- Citation
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.373, no.1, pp.58 - 63
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Volume
- 373
- Number
- 1
- Start Page
- 58
- End Page
- 63
- URI
- https://scholarworks.bwise.kr/gnu/handle/sw.gnu/27306
- DOI
- 10.1016/j.bbrc.2008.05.178
- ISSN
- 0006-291X
- Abstract
- 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.
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