Oxygen is essential for eukaryotic life and is inextricably linked to the evolution of multicellular organisms. Proper cellular response to changes in oxygen tension during normal development or pathological processes, such as cardiovascular disease and cancer, is ultimately regulated by the transcription factor, hypoxia-inducible factor (HIF). Over the past decade, unprecedented molecular insight has been gained into the mammalian oxygen-sensing pathway involving the canonical oxygen-dependent prolyl-hydroxylase domain-containing enzyme (PHD)-von Hippel-Lindau tumour suppressor protein (pVHL) axis and its connection to cellular metabolism. Here we review recent notable advances in the field of hypoxia that have shaped a more complex model of HIF regulation and revealed unique roles of HIF in a diverse range of biological processes, including immunity, development and stem cell biology. The EMBO Journal (2012) 31, 2448-2460. doi: 10.1038/emboj.2012.125; Published online 4 May 2012
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Petrovsky Natl Res Ctr Surg, Avtsyn Res Inst Human Morphol, Moscow 117418, RussiaPetrovsky Natl Res Ctr Surg, Avtsyn Res Inst Human Morphol, Moscow 117418, Russia
Dzhalilova, Dzhuliia Sh
Makarova, Olga, V
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Petrovsky Natl Res Ctr Surg, Avtsyn Res Inst Human Morphol, Moscow 117418, Russia
Lomonosov Moscow State Univ, Fac Biol, Moscow 119234, RussiaPetrovsky Natl Res Ctr Surg, Avtsyn Res Inst Human Morphol, Moscow 117418, Russia
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Chinese Peoples Liberat Army, Dept Geriatr Cardiol, Gen Hosp, Beijing, Peoples R ChinaFuWai Hosp, Dept Cardiol, Beijing 100037, Peoples R China
Gao, Linggen
Chen, Qian
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Chinese Peoples Liberat Army, Dept Geriatr Cardiol, Gen Hosp, Beijing, Peoples R ChinaFuWai Hosp, Dept Cardiol, Beijing 100037, Peoples R China
Chen, Qian
Zhou, Xianliang
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FuWai Hosp, Dept Cardiol, Beijing 100037, Peoples R China
Chinese Acad Med Sci, Cardiovasc Inst, Beijing 100730, Peoples R China
Peking Union Med Coll, Beijing 100021, Peoples R ChinaFuWai Hosp, Dept Cardiol, Beijing 100037, Peoples R China
Zhou, Xianliang
Fan, Li
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Chinese Peoples Liberat Army, Dept Geriatr Cardiol, Gen Hosp, Beijing, Peoples R ChinaFuWai Hosp, Dept Cardiol, Beijing 100037, Peoples R China
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China Acad Chinese Med Sci, Inst Basic Res Clin Med, Beijing, Peoples R ChinaChina Acad Chinese Med Sci, Inst Basic Res Clin Med, Beijing, Peoples R China
Guo, Jing
Tian, Xuefei
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Yale Sch Med, Dept Internal Med, Sect Nephrol, New Haven, CT USAChina Acad Chinese Med Sci, Inst Basic Res Clin Med, Beijing, Peoples R China
Tian, Xuefei
Liu, Huafeng
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Guangdong Med Univ, Key Lab Prevent & Management Chron Kidney Dis Zhan, Affiliated Hosp, Zhanjiang, Peoples R ChinaChina Acad Chinese Med Sci, Inst Basic Res Clin Med, Beijing, Peoples R China
Liu, Huafeng
Liu, Wei Jing
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Beijing Univ Chinese Med, Renal Res Inst, Beijing, Peoples R China
Beijing Univ Chinese Med, Key Lab Chinese Internal Med, Dongzhimen Hosp, Beijing, Peoples R ChinaChina Acad Chinese Med Sci, Inst Basic Res Clin Med, Beijing, Peoples R China