Potential coordination role between O-GlcNAcylation and epigenetics

Wu, Donglu; Cai, Yong; Jin, Jingji

doi:10.1007/s13238-017-0416-4

Cited by 41 publications

(30 citation statements)

References 96 publications

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“…Although the transcriptional implication of histone GlcNAcylation remains to be fully elucidated, it is likely that a flux through the hexosamine biosynthesis pathway affects the levels of this novel epigenetic mark. Therefore, nutrient sensing by OGT may be pivotal in the modulation of chromatin remodeling and in the regulation of gene expression [ 106 , 107 ].…”

Section: Molecular Mechanisms Involved In Regulation By Sugarsmentioning

confidence: 99%

The Sugar-Signaling Hub: Overview of Regulators and Interaction with the Hormonal and Metabolic Network

Sakr

Wang

Dédaldéchamp

et al. 2018

IJMS

180

117

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Plant growth and development has to be continuously adjusted to the available resources. Their optimization requires the integration of signals conveying the plant metabolic status, its hormonal balance, and its developmental stage. Many investigations have recently been conducted to provide insights into sugar signaling and its interplay with hormones and nitrogen in the fine-tuning of plant growth, development, and survival. The present review emphasizes the diversity of sugar signaling integrators, the main molecular and biochemical mechanisms related to the sugar-signaling dependent regulations, and to the regulatory hubs acting in the interplay of the sugar-hormone and sugar-nitrogen networks. It also contributes to compiling evidence likely to fill a few knowledge gaps, and raises new questions for the future.

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Section: Molecular Mechanisms Involved In Regulation By Sugarsmentioning

confidence: 99%

The Sugar-Signaling Hub: Overview of Regulators and Interaction with the Hormonal and Metabolic Network

Sakr

Wang

Dédaldéchamp

et al. 2018

IJMS

180

117

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“…Protein O-GlcNAcylation plays essential roles in the regulation of transcriptional activity [37][38][39][40], neuronal function [40], epigenetic regulation [41], modulation of protein-protein interactions [16], and the response to external stress factors [42]. Moreover, protein O-GlcNAcylation is very sensitive to the availability of uridine diphospho-N-acetylglucosamine, the GlcNAc donor for O-GlcNAcylation [43] and downstream metabolite of glucose, hence O-GlcNAcylation is often referred to as a nutrient sensor in cells [20, 43,44].…”

Section: Regulation Of O-glcnacylationmentioning

confidence: 99%

Crosstalk between phosphorylation and O‐GlcNAcylation: friend or foe

2018

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A wide variety of protein post-translational modifications (PTMs) decorate cellular proteins, regulating their structure, interactions and ultimately their function. The density of co-occurring PTMs on proteins can be very high, where multiple PTMs can positively or negatively influence each other's actions, termed PTM crosstalk. In this review, we highlight recent progress in the area of PTM crosstalk, whereby we focus on crosstalk between protein phosphorylation and O-GlcNAcylation. These two PTMs largely target identical (i.e., Ser and Thr) amino acids in proteins. Phosphorylation/O-GlcNAcylation crosstalk comes in many flavors, for instance by competition for the same site/residue (reciprocal crosstalk), as well as by modifications influencing each other in proximity or even distal on the protein sequence. PTM crosstalk is observed on the writers of these modifications (i.e., kinases and O-GlcNAc transferase), on the erasers (i.e., phosphatases and O-GlcNAcase), and on the readers and the substrates. We describe examples of all these different flavors of crosstalk, and additionally the methods that are emerging to better investigate in particular phosphorylation/O-GlcNAcylation crosstalk.

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“…In many OGT substrates, residues modified by O-GlcNAcylation are also subject to phosphorylation by Ser/Thr kinases, providing a link between metabolism and diverse types of cell signaling (22)(23)(24). OGT has been implicated in coupling epigenetic regulation to cell metabolism via altered histone modifications (25)(26)(27), regulation of Polycomb group proteins and other chromatin modifiers (21,28,29), and by its binding to and modification of TET DNA demethylases (19,26,30,31).…”

Section: Introductionmentioning

confidence: 99%

O-GlcNAcylation Enhances Double-Strand Break Repair, Promotes Cancer Cell Proliferation, and Prevents Therapy-Induced Senescence in Irradiated Tumors

Efimova

Appelbe

Ricco

et al. 2019

Molecular Cancer Research

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The metabolic reprogramming associated with characteristic increases in glucose and glutamine metabolism in advanced cancer is often ascribed to answering a higher demand for metabolic intermediates required for rapid tumor cell growth. Instead, recent discoveries have pointed to an alternative role for glucose and glutamine metabolites as cofactors for chromatin modifiers and other protein posttranslational modification enzymes in cancer cells. Beyond epigenetic mechanisms regulating gene expression, many chromatin modifiers also modulate DNA repair, raising the question whether cancer metabolic reprogramming may mediate resistance to genotoxic therapy and genomic instability. Our prior work had implicated N-acetyl-glucosamine (GlcNAc) formation by the hexosamine biosynthetic pathway (HBP) and resulting protein O-GlcNAcylation as a common means by which increased glucose and glutamine metabolism can drive double-strand break (DSB) repair and resistance to therapyinduced senescence in cancer cells. We have examined the effects of modulating O-GlcNAcylation on the DNA damage response (DDR) in MCF7 human mammary carcinoma in vitro and in xenograft tumors. Proteomic profiling revealed deregulated DDR pathways in cells with altered O-GlcNAcylation. Promoting protein O-GlcNAc modification by targeting O-GlcNAcase or simply treating animals with GlcNAc protected tumor xenografts against radiation. In turn, suppressing protein O-GlcNAcylation by blocking O-GlcNAc transferase activity led to delayed DSB repair, reduced cell proliferation, and increased cell senescence in vivo. Taken together, these findings confirm critical connections between cancer metabolic reprogramming, DDR, and senescence and provide a rationale to evaluate agents targeting O-GlcNAcylation in patients as a means to restore tumor sensitivity to radiotherapy. Implications: The finding that the HBP, via its impact on protein O-GlcNAcylation, is a key determinant of the DDR in cancer provides a mechanistic link between metabolic reprogramming, genomic instability, and therapeutic response and suggests novel therapeutic approaches for tumor radiosensitization.

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Potential coordination role between O-GlcNAcylation and epigenetics

Cited by 41 publications

References 96 publications

The Sugar-Signaling Hub: Overview of Regulators and Interaction with the Hormonal and Metabolic Network

The Sugar-Signaling Hub: Overview of Regulators and Interaction with the Hormonal and Metabolic Network

Crosstalk between phosphorylation and O‐GlcNAcylation: friend or foe

O-GlcNAcylation Enhances Double-Strand Break Repair, Promotes Cancer Cell Proliferation, and Prevents Therapy-Induced Senescence in Irradiated Tumors

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