期刊
FRONTIERS IN ENDOCRINOLOGY
卷 5, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fendo.2014.00230
关键词
ChREBP; FXR; glucose-sensing; O-GIcNAcylation; liver metabolism
资金
- Agence Nationale de la Recherche (Crisalis)
- Agence Nationale de la Recherche (Genopath)
- Fondation Francaise de la Recherche Medicale (FRM, Labelisation Equipe)
- EU Grant FLORINASH (FP7)
- EU Grant HEPADIP [018734]
- Region Nord-Pas-de-Calais/FEDER
- Agence Nationale de la Recherche [11 BSV1 032 01]
- European Genomic Institute for Diabetes [ANR-10-LABX-46]
Accumulating evidence suggests that O-GIcNAc transferase, an enzyme responsible for O-GIcNAc 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-GIcNAcylation 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-GIcNAcylated in response to glucose. This review discusses the importance of ChREBP and FXR modifications through O-GIcNAcylation in liver and how glucose can modify their mutual affinity and transcriptional activity.
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