Selection and analysis of a mutant cell line defective in the hypoxia-inducible factor-1 alpha-subunit (HIF-1alpha). Characterization of hif-1alpha-dependent and -independent hypoxia-inducible gene expression.
S M Wood,M. S. Wiesener,K. M. Yeates,N Okada,Christopher W. Pugh,Patrick H. Maxwell,Peter J. Ratcliffe +6 more
TLDR
The utility of mutagenesis and selection of mutant cells in the analysis of mammalian transcriptional responses to hypoxia is shown and the operation of HIF-1alpha-dependent and Hif-1 alpha-independent pathways of hypoxIA-inducible gene expression in Chinese hamster ovary cells is demonstrated.About:
This article is published in Journal of Biological Chemistry.The article was published on 1998-04-03 and is currently open access. It has received 198 citations till now. The article focuses on the topics: Chinese hamster ovary cell & Regulation of gene expression.read more
Citations
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The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Patrick H. Maxwell,Michael S. Wiesener,Gin-Wen Chang,Steven C. Clifford,Emma C. Vaux,Matthew Edward Cockman,Charles C. Wykoff,Christopher W. Pugh,Eamonn R. Maher,Peter J. Ratcliffe,Peter J. Ratcliffe +10 more
TL;DR: It is indicated that the interaction between HIF-1 and pVHL is iron dependent, and that it is necessary for the oxygen-dependent degradation of HIF α-subunits, which may underlie the angiogenic phenotype of VHL-associated tumours.
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Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis.
Peter Carmeliet,Yuval Dor,Jean-Marc Herbert,Dai Fukumura,Koen Brusselmans,Mieke Dewerchin,Michal Neeman,Françoise Bono,Rinat Abramovitch,Patrick H. Maxwell,Cameron J. Koch,Peter J. Ratcliffe,Lieve Moons,Rakesh K. Jain,Desire Collen,Eli Keshert +15 more
TL;DR: It is shown that hypoxia and hypoglycaemia reduce proliferation and increase apoptosis in wild-type (Hif-1α+/+) embryonic stem (ES) cells, but not in ES cells with inactivated HIF-1 α genes (HIF- 1α−/−), suggesting that there are at least two different adaptive responses to being deprived of oxygen and nutrients.
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.
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HIF-1: mediator of physiological and pathophysiological responses to hypoxia
TL;DR: HIF-1 appears to play a key role in the pathophysiology of cancer, cardiovascular disease, and chronic lung disease, which represent the major causes of mortality among industrialized societies.
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Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch.
TL;DR: Full induction of HIF-1α and -2α relies on the abrogation of both Pro and Asn hydroxylation, which during normoxia occur at the degradation and COOH-terminal transactivation domains, respectively.
References
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Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension
TL;DR: Hypoxia-inducible factor 1 (HIF-1) is found in mammalian cells cultured under reduced O2 tension and is necessary for transcriptional activation mediated by the erythropoietin gene enhancer in hypoxic cells.
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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
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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Hypoxia-inducible Factor 1α (HIF-1α) Protein Is Rapidly Degraded by the Ubiquitin-Proteasome System under Normoxic Conditions ITS STABILIZATION BY HYPOXIA DEPENDS ON REDOX-INDUCED CHANGES
Susana Salceda,Jaime Caro +1 more
TL;DR: Findings strongly suggest that the hypoxia induced changes in HIF-1alpha stability and subsequent gene activation are mediated by redox-induced changes.
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Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells.
TL;DR: EPAS1 expression is limited to the endothelium of mouse embryos and is capable of specifically activating the transcription of the endothelial tyrosine kinase gene Tie-2, raising the possibility that EPAS1 may represent an important regulator of vascularization, perhaps involving the regulation of endothelial cell gene expression in response to hypoxia.
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Activation of Hypoxia-inducible Transcription Factor Depends Primarily upon Redox-sensitive Stabilization of Its α Subunit
TL;DR: Results suggest that an intact redox-dependent signaling pathway is required for destablization of the HIF-1α protein, which was rapidly and drastically decreased in vivo following an abrupt increase to normal oxygen tension.