Cited by 32Cancer, Hypoxia, and MetabolismMetal-Catalyzed Oxygenation MechanismsEpigenetics and DNA Methylation

Regulation of the 2-oxoglutarate-dependent dioxygenases and implications for cancer

Vissers, Margreet C.M., Kuiper, Caroline, Dachs, Gabi U.·2014·Biochemical Society Transactions

Abstract

There is growing interest in the family of 2-OG (2-oxoglutarate)-dependent dioxygenase enzymes that catalyse the hydroxylation of a wide range of organic targets. Members of this family that regulate the cell's hypoxic response and epigenetic processes, particularly the demethylation of histones and DNA, have been identified in mammalian cells. The dependence of these enzymes on molecular oxygen and 2-OG as obligatory substrates, together with their need for iron and ascorbate as cofactors, has implications for their role as metabolic sensors. The oxygen-sensing property is utilized by the hydroxylases that regulate hypoxia-inducible factor and this has been well characterized, particularly with respect to tumour biology. However, the potential for metabolic sensing more generally is also of interest, and future research will expand our understanding of the effect of mitochondrial viability and nutrient (iron and ascorbate) supply on 2-OG-dependent dioxygenase activity.

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Crossref · 10.1042/bst20140118

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  • Vitamin C regulates the stabilization and activation of the hypoxia-inducible factor (HIF)-1 through the stimulation of regulatory hydroxylases.

    “Through the stimulation of regulatory hydroxylases, vitamin C also regulates the stabilization and activation of the hypoxia-inducible factor (HIF)-1, a metabolic sensor that controls the expression of hundreds of genes involved with cell survival and tissue remodelling, including collagenases [103,104,105].”

    From The Roles of Vitamin C in Skin Health. (2017) · cites this paper as [104]

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Authors
Vissers, M. C. M., Kuiper, C., & Dachs, G. U.
Affiliations
University of Otago (NZ)
Corresponding author
Kuiper, Caroline
Venue
Biochemical Society Transactions
Published
2014-08-01
Volume
42
Issue
4
Pages
945-951
ISSN
  • 0300-5127 (ISSN-L)
  • 1470-8752
OpenAlex
W2016242388
Cited by
32
References
48
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 5 · 2017: 4 · 2016: 3 · 2015: 1
FWCI
0.26
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemical Society Transactions (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
2-oxoglutarate-dependent dioxygenase, hydroxylase, oxygen sensing, hypoxia-inducible factor, histone demethylation, DNA demethylation, epigenetic regulation, metabolic sensing, iron cofactor, vitamin C, tumor biology, cancer
MeSH terms
Animals, Humans, Ketoglutaric Acids, Neoplasms, Dioxygenases

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