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HIF-1 mediates the Warburg effect in clear cell renal carcinoma

HIF-1 mediates the Warburg effect in clear cell renal carcinoma Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis in all metazoan species. O2-dependent hydroxylation of two proline residues in the HIF-1α subunit is necessary for the binding of the von Hippel–Lindau (VHL) protein, which is a component of a ubiquitin protein ligase that ubiquitinates HIF-1α, leading to its degradation by the proteasome. In the majority of cases of the clear cell type of renal carcinoma, both VHL genes are inactivated by mutation or epigenetic silencing, leading to dysregulated HIF-1 transcriptional activity. VHL loss-of-function leads, under aerobic conditions, to a HIF-1-dependent reprogramming of glucose and energy metabolism that includes increased glucose uptake, glycolysis, and lactate production accompanied by a reciprocal decrease in respiration. These findings delineate for the first time the molecular mechanisms underlying the Warburg effect in a human cancer. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Bioenergetics and Biomembranes Springer Journals

HIF-1 mediates the Warburg effect in clear cell renal carcinoma

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References (47)

Publisher
Springer Journals
Copyright
Copyright © 2007 by Springer Science+Business Media, LLC
Subject
Chemistry; Organic Chemistry; Animal Biochemistry; Animal Anatomy / Morphology / Histology; Biochemistry, general; Bioorganic Chemistry
ISSN
0145-479X
eISSN
1573-6881
DOI
10.1007/s10863-007-9081-2
pmid
17551816
Publisher site
See Article on Publisher Site

Abstract

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis in all metazoan species. O2-dependent hydroxylation of two proline residues in the HIF-1α subunit is necessary for the binding of the von Hippel–Lindau (VHL) protein, which is a component of a ubiquitin protein ligase that ubiquitinates HIF-1α, leading to its degradation by the proteasome. In the majority of cases of the clear cell type of renal carcinoma, both VHL genes are inactivated by mutation or epigenetic silencing, leading to dysregulated HIF-1 transcriptional activity. VHL loss-of-function leads, under aerobic conditions, to a HIF-1-dependent reprogramming of glucose and energy metabolism that includes increased glucose uptake, glycolysis, and lactate production accompanied by a reciprocal decrease in respiration. These findings delineate for the first time the molecular mechanisms underlying the Warburg effect in a human cancer.

Journal

Journal of Bioenergetics and Biomembranes – Springer Journals

Published: Jun 6, 2007

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