MLXIPL
Williams-Beuren syndrome chromosomal region 14 protein is a protein that in humans is encoded by the MLXIPL gene.[1][2] The protein is also known as Carbohydrate Response Element Binding Protein for its 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. The gene is deleted in Williams-Beuren syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at chromosome 7q11.23.[2]
Interactions
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 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.
References
Further reading
- de Luis O, Valero MC, Jurado LA (2000). "WBSCR14, a putative transcription factor gene deleted in Williams-Beuren syndrome: complete characterisation of the human gene and the mouse ortholog.". Eur. J. Hum. Genet. 8 (3): 215–22. doi:10.1038/sj.ejhg.5200435. PMID 10780788.
- Cairo S, Merla G, Urbinati F, et al. (2001). "WBSCR14, a gene mapping to the Williams--Beuren syndrome deleted region, is a new member of the Mlx transcription factor network.". Hum. Mol. Genet. 10 (6): 617–27. doi:10.1093/hmg/10.6.617. PMID 11230181.
- Kawaguchi T, Takenoshita M, Kabashima T, Uyeda K (2002). "Glucose and cAMP regulate the L-type pyruvate kinase gene by phosphorylation/dephosphorylation of the carbohydrate response element binding protein.". Proc. Natl. Acad. Sci. U.S.A. 98 (24): 13710–5. doi:10.1073/pnas.231370798. PMC 61106. PMID 11698644. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=61106.
- Kawaguchi T, Osatomi K, Yamashita H, et al. (2002). "Mechanism for fatty acid "sparing" effect on glucose-induced transcription: regulation of carbohydrate-responsive element-binding protein by AMP-activated protein kinase.". J. Biol. Chem. 277 (6): 3829–35. doi:10.1074/jbc.M107895200. PMID 11724780.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Hillman RT, Green RE, Brenner SE (2005). "An unappreciated role for RNA surveillance.". Genome Biol. 5 (2): R8. doi:10.1186/gb-2004-5-2-r8. PMC 395752. PMID 14759258. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=395752.
- Merla G, Howald C, Antonarakis SE, Reymond A (2005). "The subcellular localization of the ChoRE-binding protein, encoded by the Williams-Beuren syndrome critical region gene 14, is regulated by 14-3-3.". Hum. Mol. Genet. 13 (14): 1505–14. doi:10.1093/hmg/ddh163. PMID 15163635.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928.
- Li MV, Chang B, Imamura M, et al. (2006). "Glucose-dependent transcriptional regulation by an evolutionarily conserved glucose-sensing module.". Diabetes 55 (5): 1179–89. doi:10.2337/db05-0822. PMID 16644671.