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-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.
Department of Pharmacology, Gyeongsang Institute of Health Science, Gyeongsang National University School of Medicine, 92 Chilam-dong, Jinju 660-751, Republic of Korea.
So Young
SY
Eun
Im Sun
IS
Woo
Han-Su
HS
Jang
Hana
H
Jin
Min Young
MY
Kim
Hye Jung
HJ
Kim
Jae Heun
JH
Lee
Ki Churl
KC
Chang
Jin-Hoi
JH
Kim
Han Geuk
HG
Seo
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism*; D017313:Fenretinide / Q000494:pharmacology; D015723:Gene Library; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics; D020798:Two-Hybrid System Techniques; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D017313:Fenretinide; C472626:COX6A1 protein, human; D003576:Electron Transport Complex IV