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A HIF-1 target, ATIA, protects cells from apoptosis by modulating the mitochondrial thioredoxin, TRX2.

Swati Choksi | Yong Lin | Yelena Pobezinskaya | Li Chen | Chung Park | Michael Morgan | Tao Li | Siriporn Jitkaew | Xiumei Cao | You-Sun Kim | Hong-Sug Kim | Peter Levitt | Grace Shih | Michael Birre | Chu-Xia Deng | Zheng-Gang Liu
Molecular cell | 2011

The regulation of apoptosis is critical for controlling tissue homeostasis and preventing tumor formation and growth. Reactive oxygen species (ROS) generation plays a key role in such regulation. Here, we describe a HIF-1 target, Vasn/ATIA (anti-TNFα-induced apoptosis), which protects cells against TNFα- and hypoxia-induced apoptosis. Through the generation of ATIA knockout mice, we show that ATIA protects cells from apoptosis through regulating the function of the mitochondrial antioxidant, thioredoxin-2, and ROS generation. ATIA is highly expressed in human glioblastoma, and ATIA knockdown in glioblastoma cells renders them sensitive to hypoxia-induced apoptosis. Therefore, ATIA is not only a HIF-1 target that regulates mitochondrial redox pathways but also a potentially diagnostic marker and therapeutic target in human glioblastoma.

Pubmed ID: 21658601

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Associated grants

  • Agency: Intramural NIH HHS, United States
    Id: Z99 CA999999

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