Description
Carbohydrate response element-binding protein (ChREBP) is a member of the basic helix-loop-helix leucine zipper transcription factor family. Under conditions of low glucose, ChREBP is phosphorylated which sequesters the transcription factor in the cytoplasm. Under conditions of elevated glucose, one of its metabolites, xylulose 5-phosphate, activates Protein Phosphatase 2A (PP2A) which dephosphorylates ChREBP at Ser196. Dephosphorylated (Ser196) ChREBP translocates into the nucleus where it is further dephosphorylated at Thr666 by PP2A. The second dephosphorylation allows ChREBP to bind to the carbohydrate response element (ChRE) within the promoter of the L-type pyruvate kinase (L-PK) gene, as well as a subset of lipogenic enzymes. Activation of ChREBP by high glucose in the liver occurs independent of insulin. The inactivation of ChREBP has been proposed as a potential method for reducing obesity and also improving glucose tolerance