Oxygen Sensing by Metazoans: The Central Role of the HIF Hydroxylase Pathway
TLDR
HIF plays a central role in the transcriptional response to changes in oxygen availability and is modulated by FIH1-mediated asparagine hydroxylation, and HIF-modulatory drugs are now being developed for diverse diseases.About:
This article is published in Molecular Cell.The article was published on 2008-05-23 and is currently open access. It has received 2623 citations till now. The article focuses on the topics: Hypoxia-inducible factors & Oxygen homeostasis.read more
Citations
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ROS Function in Redox Signaling and Oxidative Stress
TL;DR: It is argued that redox biology, rather than oxidative stress, underlies physiological and pathological conditions.
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Reactive oxygen species in cancer
Geou Yarh Liou,Peter Storz +1 more
TL;DR: The generation of ROS within tumour cells, their detoxification, their cellular effects, as well as the major signalling cascades they utilize are discussed, but also an outlook on their modulation in therapeutics is provided.
Journal ArticleDOI
Hypoxia-Inducible Factors in Physiology and Medicine
TL;DR: Oxygen homeostasis represents an organizing principle for understanding metazoan evolution, development, physiology, and pathobiology and rapid progress is being made in elucidating homeostatic roles of HIFs in many physiological systems, determining pathological consequences of H IF dysregulation in chronic diseases, and investigating potential targeting of Hifs for therapeutic purposes.
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Otto Warburg's contributions to current concepts of cancer metabolism
TL;DR: Otto Warburg's observations are re-examine in relation to the current concepts of cancer metabolism as being intimately linked to alterations of mitochondrial DNA, oncogenes and tumour suppressors, and thus readily exploitable for cancer therapy.
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Aerobic Glycolysis: Meeting the Metabolic Requirements of Cell Proliferation
TL;DR: In this paper, the authors provide a detailed accounting of the biosynthetic requirements to construct a new cell and illustrate the importance of glycolysis in providing carbons to generate biomass.
References
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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
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.
Journal ArticleDOI
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
Oxygen sensing by HIF hydroxylases
TL;DR: The transcription factor HIF (hypoxia-inducible factor) has a central role in oxygen homeostasis in animals ranging from nematode worms to man and is regulated by an unprecedented signalling mechanism that involves post-translational hydroxylation.
Journal ArticleDOI
Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-α prolyl hydroxylase
Mary A. Selak,Sean M. Armour,Elaine D. MacKenzie,Houda Boulahbel,David G. Watson,Kyle D. Mansfield,Yi Pan,M. Celeste Simon,Craig B. Thompson,Eyal Gottlieb +9 more
TL;DR: A mitochondrion-to-cytosol signaling pathway that links mitochondrial dysfunction to oncogenic events is described, suggesting a mechanistic link between SDH mutations and HIF-1alpha induction, providing an explanation for the highly vascular tumors that develop in the absence of VHL mutations.
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