title: O-GlcNAcylation Links ChREBP and FXR to Glucose-Sensing.
abstract: 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.
authors: U1016, Institut Cochin, INSERM , Paris , France ; UMR 8104, CNRS , Paris , France ; Sorbonne Paris Cité, Université Paris Descartes , Paris , France.
authors: Fadila
authors: F
authors: Benhamed
authors: U1016, Institut Cochin, INSERM , Paris , France ; UMR 8104, CNRS , Paris , France ; Sorbonne Paris Cité, Université Paris Descartes , Paris , France.
authors: Gaelle
authors: G
authors: Filhoulaud
authors: European Genomic Institute for Diabetes (EGID) , Lille , France ; UMR 1011, INSERM , Lille , France ; Univ Lille 2 , Lille , France ; Institut Pasteur de Lille , Lille , France.
authors: Sandrine
authors: S
authors: Caron
authors: European Genomic Institute for Diabetes (EGID) , Lille , France ; UMR 1011, INSERM , Lille , France ; Univ Lille 2 , Lille , France ; Institut Pasteur de Lille , Lille , France.
authors: Philippe
authors: P
authors: Lefebvre
authors: European Genomic Institute for Diabetes (EGID) , Lille , France ; UMR 1011, INSERM , Lille , France ; Univ Lille 2 , Lille , France ; Institut Pasteur de Lille , Lille , France.
authors: Bart
authors: B
authors: Staels
authors: U1016, Institut Cochin, INSERM , Paris , France ; UMR 8104, CNRS , Paris , France ; Sorbonne Paris Cité, Université Paris Descartes , Paris , France.
authors: Catherine
authors: C
authors: Postic
keywords: ChREBP; FXR; O-GlcNAcylation; glucose-sensing; liver metabolism
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