General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia.
Guang L. Wang,Gregg L. Semenza +1 more
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It is demonstrated that Hif-1 DNA binding activity is also induced by hypoxia in a variety of mammalian cell lines in which the EPO gene is not transcribed, providing evidence that HIF-1 and its recognition sequence are common components of a general mammalian cellular response to Hypoxia.Abstract:
Transcription of the human erythropoietin (EPO) gene is activated in Hep3B cells exposed to hypoxia. Hypoxia-inducible factor 1 (HIF-1) is a nuclear factor whose DNA binding activity is induced by hypoxia in Hep3B cells, and HIF-1 binds at a site in the EPO gene enhancer that is required for hypoxic activation of transcription. In this paper, we demonstrate that HIF-1 DNA binding activity is also induced by hypoxia in a variety of mammalian cell lines in which the EPO gene is not transcribed. The composition of the HIF-1 DNA binding complex and its isolated DNA binding subunit and the mechanism of HIF-1 activation appear to be similar or identical in EPO-producing and non-EPO-producing cells. Transcription of reporter genes containing the EPO gene enhancer is induced by hypoxia in non-EPO-producing cells and mutations that eliminate HIF-1 binding eliminate inducibility. These results provide evidence that HIF-1 and its recognition sequence are common components of a general mammalian cellular response to hypoxia.read more
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Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1.
Jo A. Forsythe,Bing-Hua Jiang,Narayan V. Iyer,Faton Agani,Sandra W. Leung,Robert D. Koos,Gregg L. Semenza +6 more
TL;DR: HIF-1 is implicate in the activation of VEGF transcription in hypoxic cells and this work demonstrates the involvement of Hif-1 in theactivation of V EGF transcription.
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HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia
TL;DR: A hypoxia-induced metabolic switch that shunts glucose metabolites from the mitochondria to glycolysis to maintain ATP production and to prevent toxic ROS production is revealed.
Journal ArticleDOI
Purification and Characterization of Hypoxia-inducible Factor 1
Guang L. Wang,Gregg L. Semenza +1 more
TL;DR: The biochemical purification of HIF-1 from Epo-producing Hep3B cells and non-Epo-producing HeLa S3 cells concludes that in both cobalt chloride-treated HeLa cells and hypoxic Hep3 B cells HIF -1 is composed of two different subunits: 120-kDa Hif-1α and 91-94-k da HIF,1β.
Journal ArticleDOI
HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption
TL;DR: It is shown by genetic means that HIF-1-dependent block to oxygen utilization results in increased oxygen availability, decreased cell death when total oxygen is limiting, and reduced cell death in response to the hypoxic cytotoxin tirapazamine.
Journal ArticleDOI
Regulation of mammalian o2 homeostasis by hypoxia-inducible factor 1
TL;DR: HIF-1 appears to function as a master regulator of O2 homeostasis that plays essential roles in cellular and systemic physiology, development, and pathophysiology.
References
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Journal ArticleDOI
A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation.
Gregg L. Semenza,Guang L. Wang +1 more
TL;DR: A functionally tripartite, 50-nt hypoxia-inducible enhancer which binds several nuclear factors, one of which is induced by Hypoxia via de novo protein synthesis.
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A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation.
Gregg L. Semenza,Guang L. Wang +1 more