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O-GlcNAcylation Links ChREBP and FXR to Glucose-Sensing
Accumulating evidence suggests that O-GlcNAc transferase, an enzyme responsible for O-GlcNAc post-translational modification acts as a nutrient sensor that links glucose and the hexosamine biosynthetic pathway to the regulation of transcriptional factors involved in energy homeostasis. In liver, glu...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4292737/ https://www.ncbi.nlm.nih.gov/pubmed/25628602 http://dx.doi.org/10.3389/fendo.2014.00230 |
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author | Benhamed, Fadila Filhoulaud, Gaelle Caron, Sandrine Lefebvre, Philippe Staels, Bart Postic, Catherine |
author_facet | Benhamed, Fadila Filhoulaud, Gaelle Caron, Sandrine Lefebvre, Philippe Staels, Bart Postic, Catherine |
author_sort | Benhamed, Fadila |
collection | PubMed |
description | Accumulating evidence suggests that O-GlcNAc transferase, an enzyme responsible for O-GlcNAc post-translational modification acts as a nutrient sensor that links glucose and the hexosamine biosynthetic pathway to the regulation of transcriptional factors involved in energy homeostasis. In liver, glucose signaling is mediated by carbohydrate response element-binding protein (ChREBP), which stimulates glycolytic and lipogenic gene expression through its binding on a specific ChoRE DNA sequence. Modulation of ChREBP by O-GlcNAcylation increases its DNA binding affinity and its activity. ChREBP transcriptional activity also depends on the presence of several other co-factors and transcriptional factors. Among them, the nuclear Farnesoid X Receptor (FXR), a key transcription factor of bile acid metabolism involved in the gut–liver axis homeostasis was recently shown to directly interact with ChREBP, acting as a repressor on the ChoRE of glycolytic genes. Interestingly, similarly to ChREBP, FXR is O-GlcNAcylated in response to glucose. This review discusses the importance of ChREBP and FXR modifications through O-GlcNAcylation in liver and how glucose can modify their mutual affinity and transcriptional activity. |
format | Online Article Text |
id | pubmed-4292737 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-42927372015-01-27 O-GlcNAcylation Links ChREBP and FXR to Glucose-Sensing Benhamed, Fadila Filhoulaud, Gaelle Caron, Sandrine Lefebvre, Philippe Staels, Bart Postic, Catherine Front Endocrinol (Lausanne) Endocrinology Accumulating evidence suggests that O-GlcNAc transferase, an enzyme responsible for O-GlcNAc post-translational modification acts as a nutrient sensor that links glucose and the hexosamine biosynthetic pathway to the regulation of transcriptional factors involved in energy homeostasis. In liver, glucose signaling is mediated by carbohydrate response element-binding protein (ChREBP), which stimulates glycolytic and lipogenic gene expression through its binding on a specific ChoRE DNA sequence. Modulation of ChREBP by O-GlcNAcylation increases its DNA binding affinity and its activity. ChREBP transcriptional activity also depends on the presence of several other co-factors and transcriptional factors. Among them, the nuclear Farnesoid X Receptor (FXR), a key transcription factor of bile acid metabolism involved in the gut–liver axis homeostasis was recently shown to directly interact with ChREBP, acting as a repressor on the ChoRE of glycolytic genes. Interestingly, similarly to ChREBP, FXR is O-GlcNAcylated in response to glucose. This review discusses the importance of ChREBP and FXR modifications through O-GlcNAcylation in liver and how glucose can modify their mutual affinity and transcriptional activity. Frontiers Media S.A. 2015-01-13 /pmc/articles/PMC4292737/ /pubmed/25628602 http://dx.doi.org/10.3389/fendo.2014.00230 Text en Copyright © 2015 Benhamed, Filhoulaud, Caron, Lefebvre, Staels and Postic. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology Benhamed, Fadila Filhoulaud, Gaelle Caron, Sandrine Lefebvre, Philippe Staels, Bart Postic, Catherine O-GlcNAcylation Links ChREBP and FXR to Glucose-Sensing |
title | O-GlcNAcylation Links ChREBP and FXR to Glucose-Sensing |
title_full | O-GlcNAcylation Links ChREBP and FXR to Glucose-Sensing |
title_fullStr | O-GlcNAcylation Links ChREBP and FXR to Glucose-Sensing |
title_full_unstemmed | O-GlcNAcylation Links ChREBP and FXR to Glucose-Sensing |
title_short | O-GlcNAcylation Links ChREBP and FXR to Glucose-Sensing |
title_sort | o-glcnacylation links chrebp and fxr to glucose-sensing |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4292737/ https://www.ncbi.nlm.nih.gov/pubmed/25628602 http://dx.doi.org/10.3389/fendo.2014.00230 |
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