The small members of the JMJD protein family: Enzymatic jewels or jinxes?

Oh, Sangphil; Shin, Sook; Janknecht, Ralf

doi:10.1016/j.bbcan.2019.04.002

Cited by 44 publications

(47 citation statements)

References 197 publications

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“…Most are known, or predicted, to catalyse protein hydroxylation, as opposed to the demethylation via hydroxylation reaction catalysed by JmjC KDMs (Figure 2). However, members of this sub-family are poorly understood and represent an evolving area of research as the precise biological functions and physiological substrates of several of these JmjC-only enzymes are uncertain [17].…”

Section: Og-oxygenasesmentioning

confidence: 99%

“…Many studies have investigated how 2OG-oxygenases behave in cancer. The reader is referred to [5,11,17,108] for more detailed reviews. For some enzymes, for example, TET2 and the KDM4 sub-family, their role is relatively clear-cut.…”

Section: Og-oxygenases: Disease Mediatorsmentioning

confidence: 99%

“…In fact, TET2 is one of the most commonly mutated genes in AML [110]. For other 2OG-oxygenases however, particularly those in the JmjC-only sub-family, the picture is less clear [17,111]. In the case of arginyl hydroxylase JMJD5, for example, multiple studies have described both pro-and antitumourigenic functions.…”

Section: Og-oxygenases: Disease Mediatorsmentioning

confidence: 99%

“…One of the major challenges in the hydroxylation field is resolving controversies over the biochemical assignment of some 2OG-oxygenases, particularly in the JmjC-only sub-family [17]. For example, different studies have attributed histone demethylase and histone tail clipping activity to JMJD5 [94,112,121], whilst detailed biochemical and structural studies indicate that it functions as a protein hydroxylase [91,122].…”

Section: Activity Assignment Controversymentioning

confidence: 99%

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

Fletcher

Coleman

2020

Biochemical Society Transactions

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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.

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Section: Og-oxygenasesmentioning

confidence: 99%

Section: Og-oxygenases: Disease Mediatorsmentioning

confidence: 99%

Section: Og-oxygenases: Disease Mediatorsmentioning

confidence: 99%

Section: Activity Assignment Controversymentioning

confidence: 99%

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

Fletcher

Coleman

2020

Biochemical Society Transactions

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“…JMJD1C, a histone demethylase 44 , regulated chondroitin and dermatan sulfate extension by its interaction with two GalNAc transferases: CSGALNACT2 and CHSY1. It also interacts with genes regulating GAG initiation.…”

Section: Critical Role For Runx3 In Terminal Fucosylationmentioning

confidence: 99%

A systems based framework to computationally predict putative transcription factors and signaling pathways regulating glycan biosynthesis

Groth¹,

Neelamegham

2020

Preprint

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Glycosylation is a common, complex, non-linear post-translational modification. The biosynthesis of these structures is regulated by a set of 'glycogenes'. The role of transcription factors (TFs) in regulating the glycogenes and related glycosylation pathways is yet unknown. This manuscript presents a multi-OMICs data-mining framework to computationally predict tissue specific TF activities and cell signaling pathways regulating the biosynthesis of specific glycan structures. It combines existing ChIP-Seq (Chromatin ImmunoPrecipitation Sequencing) and RNA-Seq data to reveal 20,617 potentially significant TF-glycogene relationships. This includes interactions involving 524 unique TFs and 341 glycogenes that span 29 TCGA (The Cancer Genome Atlas) cancer types. Here, TF-glycogene interactions appeared in clusters or 'communities', suggesting that they may collectively drive changes in sets of carbohydrate structures rather than unique glycans as disease progresses. Upon applying the Fisher's exact test along with glycogene pathway ontology, we identify TFs that may specifically regulate the biosynthesis of individual glycan types. Integration with knowledge from the Reactome database established the link between cell signaling pathways, transcription factors, glycogene expression, and glycosylation pathways. Whereas analysis results are presented for all 29 cancer types, specific focus is placed on human luminal and basal breast cancer disease progression. This implicates a key role for TGF-β and Wnt signaling in regulating TFs that control both tumorigenesis and cellular glycosylation. Overall, the computational predictions in this manuscript present a rich dataset that is ripe for experimental testing and hypotheses validation.

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Exploring links between 2‐oxoglutarate‐dependent oxygenases and Alzheimer's disease

Liu

Xie

Wang

et al. 2022

Alzheimer's & Dementia

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Hypoxia, that is, an inadequate oxygen supply, is linked to neurodegeneration and patients with cardiovascular disease are prone to Alzheimer's disease (AD). 2‐Oxoglutarate and ferrous iron‐dependent oxygenases (2OGDD) play a key role in the regulation of oxygen homeostasis by acting as hypoxia sensors. 2OGDD also have roles in collagen biosynthesis, lipid metabolism, nucleic acid repair, and the regulation of transcription and translation. Many biological processes in which the >60 human 2OGDD are involved are altered in AD patient brains, raising the question as to whether 2OGDD are involved in the transition from normal aging to AD. Here we give an overview of human 2OGDD and critically discuss their potential roles in AD, highlighting possible relationships with synapse dysfunction/loss. 2OGDD may regulate neuronal/glial differentiation through enzyme activity‐dependent mechanisms and modulation of their activity has potential to protect against synapse loss. Work linking 2OGDD and AD is at an early stage, especially from a therapeutic perspective; we suggest integrated pathology and in vitro discovery research to explore their roles in AD is merited. We hope to help enable long‐term research on the roles of 2OGDD and, more generally, oxygen/hypoxia in AD. We also suggest shorter term empirically guided clinical studies concerning the exploration of 2OGDD/oxygen modulators to help maintain synaptic viability are of interest for AD treatment.

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The small members of the JMJD protein family: Enzymatic jewels or jinxes?

Cited by 44 publications

References 197 publications

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

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

A systems based framework to computationally predict putative transcription factors and signaling pathways regulating glycan biosynthesis

Exploring links between 2‐oxoglutarate‐dependent oxygenases and Alzheimer's disease

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