Activation of hypoxia-inducible factor-1; definition of regulatory domains within the alpha subunit.
TLDR
A dual mechanism of activation is proposed in which the operation of an inducible activation domain is amplified by regulation of transcription factor abundance, most likely occurring through changes in protein stability.About:
This article is published in Journal of Biological Chemistry.The article was published on 1997-04-25 and is currently open access. It has received 537 citations till now. The article focuses on the topics: Binding domain & DNA-binding domain.read more
Citations
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Journal ArticleDOI
Targeting HIF-1 for cancer therapy
TL;DR: Hypoxia-inducible factor 1 (HIF-1) activates the transcription of genes that are involved in crucial aspects of cancer biology, including angiogenesis, cell survival, glucose metabolism and invasion.
Journal ArticleDOI
Targeting of HIF-alpha to the von Hippel-Lindau Ubiquitylation Complex by O2-Regulated Prolyl Hydroxylation
Panu Jaakkola,David R. Mole,Ya-Min Tian,Michael I. Wilson,Janine Gielbert,Simon J. Gaskell,Alex von Kriegsheim,Holger F. Hebestreit,Mridul Mukherji,Christopher J. Schofield,Patrick H. Maxwell,Christopher W. Pugh,Peter J. Ratcliffe +12 more
TL;DR: It is shown that the interaction between human pVHL and a specific domain of the HIF-1α subunit is regulated through hydroxylation of a proline residue by an enzyme the authors have termed Hif-α prolyl-hydroxylase (HIF-PH).
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HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O2 Sensing
Mircea Ivan,Keiichi Kondo,Haifeng Yang,William Y. Kim,Jennifer Valiando,Michael Ohh,Adrian Salic,John M. Asara,William S. Lane,William G. Kaelin,William G. Kaelin +10 more
TL;DR: It is found that human pVHL binds to a short HIF-derived peptide when a conserved proline residue at the core of this peptide is hydroxylated, which may play a key role in mammalian oxygen sensing.
Journal ArticleDOI
Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1α
Narayan V. Iyer,Lori E. Kotch,Faton Agani,Sandra W. Leung,Erik Laughner,Roland H. Wenger,Max Gassmann,John D. Gearhart,Ann M. Lawler,Aimee Y. Yu,Gregg L. Semenza +10 more
TL;DR: It is demonstrated that HIF-1alpha is a master regulator of cellular and developmental O2 homeostasis in Hif1a-/- embryos that manifested neural tube defects, cardiovascular malformations, and marked cell death within the cephalic mesenchyme.
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Regulation of hypoxia-inducible factor 1α is mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway
TL;DR: The identification of an oxygen-dependent degradation (ODD) domain within HIF-1alpha that controls its degradation by the ubiquitin-proteasome pathway is reported and may provide a means of controlling gene expression by changes in oxygen tension.
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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Rapid detection of octamer binding proteins with ‘mini extracts’, prepared from a small number of cells
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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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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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Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1.
TL;DR: In this article, the role of HIF-1 as a mediator of adaptive responses to hypoxia that underlie cellular and systemic oxygen homeostasis was investigated in Hep3B cells.