Carbohydrate-responsive element-binding protein (ChREBP) also known as MLX-interacting protein-like (MLXIPL) is a
protein that in humans is encoded by the MLXIPLgene.[5][6] The protein name derives from the protein's interaction with carbohydrate response element sequences of DNA.
Function
Domains of ChREBP. The N-terminal glucose-sensing module consists of the low glucose inhibitory domain (LID) and the glucose activated conserved element (GRACE). The C-terminal regions consists of a polyproline-rich, a bHLH/LZ and a leucine-zipper-like (Zip-like) domain. Phosphorylation sites in red, acetylation sites in blue and O-GlcNAcylation sites in green.[7]
This gene is deleted in
Williams-Beuren syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at chromosome 7q11.23.[6]
Chronically elevated blood glucose can activate ChREBP in the
pancreas can lead to excessive lipid synthesis in
beta cells, increasing lipid accumulation in those cells, leading to
lipotoxicity, beta-cell
apoptosis, and type 2 diabetes.[10]
ChREBP is translocated to the nucleus and binds to DNA after dephosphorylation of a p-Ser and a p-Thr residue by
PP2A, which itself is activated by
xylulose-5-phosphate. Xu5p is produced in the
pentose phosphate pathway when levels of
Glucose-6-phosphate are high (the cell has ample glucose). In the liver, ChREBP mediates activation of several regulatory enzymes of glycolysis and lipogenesis including L-type pyruvate kinase (L-PK), acetyl CoA carboxylase, and fatty acid synthase.
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Meng X, Lu X, Li Z, Green ED, Massa H, Trask BJ, et al. (November 1998). "Complete physical map of the common deletion region in Williams syndrome and identification and characterization of three novel genes". Human Genetics. 103 (5): 590–599.
doi:
10.1007/s004390050874.
PMID9860302.
S2CID23530406.