Carbohydrate-responsive element-binding protein (ChREBP) also known as MLX-interacting protein-like (MLXIPL) is a protein that in humans is encoded by the MLXIPL gene. [5] [6] The protein name derives from the protein's interaction with carbohydrate response element sequences of DNA.
This gene encodes a basic helix-loop-helix leucine zipper transcription factor of the Myc / Max / Mad superfamily. This protein forms a heterodimeric complex and binds and activates, in a glucose-dependent manner, carbohydrate response element (ChoRE) motifs in the promoters of triglyceride synthesis genes. [6]
ChREBP is activated by glucose, independent of insulin. [8] In adipose tissue, ChREBP induces de novo lipogenesis from glucose in response to a glucose flux into adipocytes. [9] [8] In the liver, glucose induction of ChREBP promotes glycolysis and lipogenesis. [8]
This gene is deleted in Williams-Beuren syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at chromosome 7q11.23. [6]
Excess expression of ChREBP in the liver due to metabolic syndrome or type 2 diabetes can lead to steatosis in the liver. [8] In non-alcoholic fatty liver disease, about 25% of total liver lipids result from de novo synthesis (synthesis of lipids from glucose). [7] High blood glucose and insulin enhance lipogenesis in the liver by activation of ChREBP and SREBP-1c, respectively. [7]
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]
MLXIPL has been shown to interact with MLX. [11]
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.
MLXIPL | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | MLXIPL, CHREBP, MIO, MONDOB, WBSCR14, WS-bHLH, bHLHd14, MLX interacting protein like, MLX | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 605678; MGI: 1927999; HomoloGene: 32507; GeneCards: MLXIPL; OMA: MLXIPL - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Carbohydrate-responsive element-binding protein (ChREBP) also known as MLX-interacting protein-like (MLXIPL) is a protein that in humans is encoded by the MLXIPL gene. [5] [6] The protein name derives from the protein's interaction with carbohydrate response element sequences of DNA.
This gene encodes a basic helix-loop-helix leucine zipper transcription factor of the Myc / Max / Mad superfamily. This protein forms a heterodimeric complex and binds and activates, in a glucose-dependent manner, carbohydrate response element (ChoRE) motifs in the promoters of triglyceride synthesis genes. [6]
ChREBP is activated by glucose, independent of insulin. [8] In adipose tissue, ChREBP induces de novo lipogenesis from glucose in response to a glucose flux into adipocytes. [9] [8] In the liver, glucose induction of ChREBP promotes glycolysis and lipogenesis. [8]
This gene is deleted in Williams-Beuren syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at chromosome 7q11.23. [6]
Excess expression of ChREBP in the liver due to metabolic syndrome or type 2 diabetes can lead to steatosis in the liver. [8] In non-alcoholic fatty liver disease, about 25% of total liver lipids result from de novo synthesis (synthesis of lipids from glucose). [7] High blood glucose and insulin enhance lipogenesis in the liver by activation of ChREBP and SREBP-1c, respectively. [7]
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]
MLXIPL has been shown to interact with MLX. [11]
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.