Identification of cytochrome c oxidase subunit 6A1 as a suppressor of Bax-induced cell death by yeast-based functional screening

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-hydroxyph...

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Published in:Biochemical and biophysical research communications 2008-08, Vol.373 (1), p.58-63
Main 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
Format: Article
Language:English
Subjects:
4-HPR
Antineoplastic Agents - pharmacology
Apoptosis
Bax
bcl-2-Associated X Protein - genetics
bcl-2-Associated X Protein - metabolism
Cell Line, Tumor
COX6A1
Electron Transport Complex IV - genetics
Electron Transport Complex IV - metabolism
Fenretinide - pharmacology
Gene Library
Humans
JNK
Reactive Oxygen Species - metabolism
ROS
Saccharomyces cerevisiae - cytology
Saccharomyces cerevisiae - genetics
Two-Hybrid System Techniques
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2008.05.178