Carbohydrate-responsive element-binding protein
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.
Function
This gene encodes a
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]
Clinical significance
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
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]
Interactions
MLXIPL has been shown to
Role in glycolysis
ChREBP is translocated to the nucleus and binds to DNA after dephosphorylation of a p-Ser and a p-Thr residue by
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000009950 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000005373 - Ensembl, May 2017
- ^ "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.
- S2CID 23530406.
- ^ a b c "Entrez Gene: MLXIPL MLX interacting protein-like".
- ^ PMID 31275349.
- ^ PMID 24222088.
- PMID 23443243.
- PMID 31623194.
- PMID 11230181.
Further reading
- de Luis O, Valero MC, Jurado LA (March 2000). "WBSCR14, a putative transcription factor gene deleted in Williams-Beuren syndrome: complete characterisation of the human gene and the mouse ortholog". European Journal of Human Genetics. 8 (3): 215–222. PMID 10780788.
- Kawaguchi T, Takenoshita M, Kabashima T, Uyeda K (November 2001). "Glucose and cAMP regulate the L-type pyruvate kinase gene by phosphorylation/dephosphorylation of the carbohydrate response element binding protein". Proceedings of the National Academy of Sciences of the United States of America. 98 (24): 13710–13715. PMID 11698644.
- Kawaguchi T, Osatomi K, Yamashita H, Kabashima T, Uyeda K (February 2002). "Mechanism for fatty acid "sparing" effect on glucose-induced transcription: regulation of carbohydrate-responsive element-binding protein by AMP-activated protein kinase". The Journal of Biological Chemistry. 277 (6): 3829–3835. PMID 11724780.
- Hillman RT, Green RE, Brenner SE (2005). "An unappreciated role for RNA surveillance". Genome Biology. 5 (2): R8. PMID 14759258.
- Merla G, Howald C, Antonarakis SE, Reymond A (July 2004). "The subcellular localization of the ChoRE-binding protein, encoded by the Williams-Beuren syndrome critical region gene 14, is regulated by 14-3-3". Human Molecular Genetics. 13 (14): 1505–1514. PMID 15163635.
- Li MV, Chang B, Imamura M, Poungvarin N, Chan L (May 2006). "Glucose-dependent transcriptional regulation by an evolutionarily conserved glucose-sensing module". Diabetes. 55 (5): 1179–1189. PMID 16644671.