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

TitleA HIF-1 target, ATIA, protects cells from apoptosis by modulating the mitochondrial thioredoxin, TRX2.
Publication TypeJournal Article
Year of Publication2011
AuthorsChoksi S, Lin Y, Pobezinskaya Y, Chen L, Park C, Morgan M, Li T, Jitkaew S, Cao X, Kim Y-S, Kim H-S, Levitt P, Shih G, Birre M, Deng C-X, Liu Z-G
JournalMol Cell
Volume42
Issue5
Pagination597-609
Date Published2011 Jun 10
ISSN1097-4164
KeywordsAnimals, Apoptosis, Apoptosis Regulatory Proteins, Carrier Proteins, Cell Hypoxia, Cell Line, Tumor, Cell Membrane, Glioblastoma, Humans, Hypoxia-Inducible Factor 1, Membrane Proteins, Mice, Mitochondria, Oxidation-Reduction, Thioredoxins
Abstract

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.

DOI10.1016/j.molcel.2011.03.030
Alternate JournalMol. Cell
PubMed ID21658601