缺氧诱导因子 1（HIF-1）的一个靶标 ATIA 通过调节线粒体硫氧还蛋白（TRX2）来保护细胞免于凋亡。
A HIF-1 target, ATIA, protects cells from apoptosis by modulating the mitochondrial thioredoxin, TRX2.
机构信息
Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA.
出版信息
Mol Cell. 2011 Jun 10;42(5):597-609. doi: 10.1016/j.molcel.2011.03.030.
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.
摘要
细胞凋亡的调控对于控制组织内稳态和防止肿瘤的形成和生长至关重要。活性氧（ROS）的产生在这种调控中起着关键作用。在这里，我们描述了一个 HIF-1 靶标，Vasn/ATIA（抗 TNFα 诱导的细胞凋亡），它可以保护细胞免受 TNFα 和缺氧诱导的细胞凋亡。通过生成 ATIA 敲除小鼠，我们发现 ATIA 通过调节线粒体抗氧化剂硫氧还蛋白-2 的功能和 ROS 的产生来保护细胞免受凋亡。ATIA 在人神经胶质瘤中高度表达，并且在神经胶质瘤细胞中敲低 ATIA 可使其对缺氧诱导的细胞凋亡敏感。因此，ATIA 不仅是调节线粒体氧化还原途径的 HIF-1 靶标，也是人神经胶质瘤中潜在的诊断标志物和治疗靶标。
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