Human 2-oxoglutarate-dependent oxygenases: nutrient sensors, stress responders, and disease mediators

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Human 2-oxoglutarate-dependent oxygenases : nutrient sensors, stress responders, and disease mediators. / Fletcher, Sally C; Coleman, Mathew L.

In: Biochemical Society Transactions, Vol. 48, No. 5, 10.2020, p. 1843-1858.

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@article{52eb41989ce1402da20a35addf9cfa77,
title = "Human 2-oxoglutarate-dependent oxygenases: nutrient sensors, stress responders, and disease mediators",
abstract = "Fe(II)/2-oxoglutarate (2OG)-dependent oxygenases are a conserved enzyme class that catalyse diverse oxidative reactions across nature. In humans, these enzymes hydroxylate a broad range of biological substrates including DNA, RNA, proteins and some metabolic intermediates. Correspondingly, members of the 2OG-dependent oxygenase superfamily have been linked to fundamental biological processes, and found dysregulated in numerous human diseases. Such findings have stimulated efforts to understand both the biochemical activities and cellular functions of these enzymes, as many have been poorly studied. In this review, we focus on human 2OG-dependent oxygenases catalysing the hydroxylation of protein and polynucleotide substrates. We discuss their modulation by changes in the cellular microenvironment, particularly with respect to oxygen, iron, 2OG and the effects of oncometabolites. We also describe emerging evidence that these enzymes are responsive to cellular stresses including hypoxia and DNA damage. Moreover, we examine how dysregulation of 2OG-dependent oxygenases is associated with human disease, and the apparent paradoxical role for some of these enzymes during cancer development. Finally, we discuss some of the challenges associated with assigning biochemical activities and cellular functions to 2OG-dependent oxygenases.",
author = "Fletcher, {Sally C} and Coleman, {Mathew L}",
note = "{\textcopyright} 2020 The Author(s).",
year = "2020",
month = oct,
doi = "10.1042/BST20190333",
language = "English",
volume = "48",
pages = "1843--1858",
journal = "Biochemical Society Transactions",
issn = "1470-8752",
publisher = "Portland Press",
number = "5",

}

RIS

TY - JOUR

T1 - Human 2-oxoglutarate-dependent oxygenases

T2 - nutrient sensors, stress responders, and disease mediators

AU - Fletcher, Sally C

AU - Coleman, Mathew L

N1 - © 2020 The Author(s).

PY - 2020/10

Y1 - 2020/10

N2 - Fe(II)/2-oxoglutarate (2OG)-dependent oxygenases are a conserved enzyme class that catalyse diverse oxidative reactions across nature. In humans, these enzymes hydroxylate a broad range of biological substrates including DNA, RNA, proteins and some metabolic intermediates. Correspondingly, members of the 2OG-dependent oxygenase superfamily have been linked to fundamental biological processes, and found dysregulated in numerous human diseases. Such findings have stimulated efforts to understand both the biochemical activities and cellular functions of these enzymes, as many have been poorly studied. In this review, we focus on human 2OG-dependent oxygenases catalysing the hydroxylation of protein and polynucleotide substrates. We discuss their modulation by changes in the cellular microenvironment, particularly with respect to oxygen, iron, 2OG and the effects of oncometabolites. We also describe emerging evidence that these enzymes are responsive to cellular stresses including hypoxia and DNA damage. Moreover, we examine how dysregulation of 2OG-dependent oxygenases is associated with human disease, and the apparent paradoxical role for some of these enzymes during cancer development. Finally, we discuss some of the challenges associated with assigning biochemical activities and cellular functions to 2OG-dependent oxygenases.

AB - Fe(II)/2-oxoglutarate (2OG)-dependent oxygenases are a conserved enzyme class that catalyse diverse oxidative reactions across nature. In humans, these enzymes hydroxylate a broad range of biological substrates including DNA, RNA, proteins and some metabolic intermediates. Correspondingly, members of the 2OG-dependent oxygenase superfamily have been linked to fundamental biological processes, and found dysregulated in numerous human diseases. Such findings have stimulated efforts to understand both the biochemical activities and cellular functions of these enzymes, as many have been poorly studied. In this review, we focus on human 2OG-dependent oxygenases catalysing the hydroxylation of protein and polynucleotide substrates. We discuss their modulation by changes in the cellular microenvironment, particularly with respect to oxygen, iron, 2OG and the effects of oncometabolites. We also describe emerging evidence that these enzymes are responsive to cellular stresses including hypoxia and DNA damage. Moreover, we examine how dysregulation of 2OG-dependent oxygenases is associated with human disease, and the apparent paradoxical role for some of these enzymes during cancer development. Finally, we discuss some of the challenges associated with assigning biochemical activities and cellular functions to 2OG-dependent oxygenases.

U2 - 10.1042/BST20190333

DO - 10.1042/BST20190333

M3 - Article

C2 - 32985654

VL - 48

SP - 1843

EP - 1858

JO - Biochemical Society Transactions

JF - Biochemical Society Transactions

SN - 1470-8752

IS - 5

ER -