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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 expres-sion 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 fac-tors. 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.
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Submitted on : Wednesday, January 14, 2015 - 3:49:44 PM
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Fadila Benhamed, Gaelle Filhoulaud, Sandrine Caron, Philippe Lefebvre, Bart Staels, et al.. O-GlcNAcylation links ChREBP and FXR to glucose-sensing. Frontiers in Endocrinology, Frontiers, 2015, pp.230. ⟨10.3389/fendo.2014.00230⟩. ⟨inserm-01103380⟩

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