title: A HIF-1 target, ATIA, protects cells from apoptosis by modulating the mitochondrial thioredoxin, TRX2.
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.
authors.affiliation: Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Swati
authors.initials: S
authors.lastname: Choksi
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.forename: Yelena
authors.initials: Y
authors.lastname: Pobezinskaya
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Chung
authors.initials: C
authors.lastname: Park
authors.forename: Michael
authors.initials: M
authors.lastname: Morgan
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Siriporn
authors.initials: S
authors.lastname: Jitkaew
authors.forename: Xiumei
authors.initials: X
authors.lastname: Cao
authors.forename: You-Sun
authors.initials: YS
authors.lastname: Kim
authors.forename: Hong-Sug
authors.initials: HS
authors.lastname: Kim
authors.forename: Peter
authors.initials: P
authors.lastname: Levitt
authors.forename: Grace
authors.initials: G
authors.lastname: Shih
authors.forename: Michael
authors.initials: M
authors.lastname: Birre
authors.forename: Chu-Xia
authors.initials: CX
authors.lastname: Deng
authors.forename: Zheng-Gang
authors.initials: ZG
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D005909:Glioblastoma / Q000378:metabolism; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D051793:Hypoxia-Inducible Factor 1; D008565:Membrane Proteins; C488722:VASN protein, human; C560425:Vasn protein, mouse; D013879:Thioredoxins