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F r o m W i k i p e d i a , t h e f r e e e n c y c l o p e d i a
( R e d i r e c t e d f r o m C h R E B P )
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]
Function
[ edit ] 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 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] glycolysis and lipogenesis .[8]
Clinical significance
[ edit ]
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] 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]
Interactions
[ edit ]
MLXIPL has been shown to interact with MLX .[11]
Role in glycolysis
[ edit ]
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
[ edit ]
^ "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 . PMID 9860302 . S2CID 23530406 .
^ a b c "Entrez Gene: MLXIPL MLX interacting protein-like" .
^ a b c Ortega-Prieto P, Postic C (2019). "Carbohydrate Sensing Through the Transcription Factor ChREBP" . Frontiers in Genetics . 10 doi :10.3389/fgene.2019.00472 PMC 6593282 PMID 31275349 .
^ a b c d Xu X, So JS, Park JG, Lee AH (November 2013). "Transcriptional control of hepatic lipid metabolism by SREBP and ChREBP" . Seminars in Liver Disease . 33 4 ): 301–311. doi :10.1055/s-0033-1358523 . PMC 4035704 PMID 24222088 .
^ Czech MP, Tencerova M, Pedersen DJ, Aouadi M (May 2013). "Insulin signalling mechanisms for triacylglycerol storage" . Diabetologia . 56 5 ): 949–964. doi :10.1007/s00125-013-2869-1 . PMC 3652374 PMID 23443243 .
^ Song Z, Yang H, Zhou L, Yang F (October 2019). "Glucose-Sensing Transcription Factor MondoA/ChREBP as Targets for Type 2 Diabetes: Opportunities and Challenges" . International Journal of Molecular Sciences . 20 20 ): E5132. doi :10.3390/ijms20205132 PMC 6829382 PMID 31623194 .
^ Cairo S, Merla G, Urbinati F, Ballabio A, Reymond A (March 2001). "WBSCR14, a gene mapping to the Williams--Beuren syndrome deleted region, is a new member of the Mlx transcription factor network" . Human Molecular Genetics . 10 6 ): 617–627. doi :10.1093/hmg/10.6.617 PMID 11230181 .
Further reading
[ edit ]
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. Bibcode :2001PNAS...9813710K . doi :10.1073/pnas.231370798 PMC 61106 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. doi :10.1074/jbc.M107895200 PMID 11724780 .
Hillman RT, Green RE, Brenner SE (2005). "An unappreciated role for RNA surveillance" . Genome Biology . 5 2 ): R8. doi :10.1186/gb-2004-5-2-r8 PMC 395752 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. doi :10.1093/hmg/ddh163 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. doi :10.2337/db05-0822 PMID 16644671 .
t
e
(1 ) Basic domains
(1.1) Basic leucine zipper (bZIP )
(1.2) Basic helix-loop-helix (bHLH )
Group A
Group B
Group CPAS
Group D
Group E
Group F
(1.3) bHLH-ZIP
(1.4) NF-1
(1.5) RF-X
(1.6) Basic helix-span-helix (bHSH)
(2 ) Zinc finger DNA-binding domains
(2.1) Nuclear receptor (Cys4
subfamily 1
subfamily 2
subfamily 3
subfamily 4
subfamily 5
subfamily 6
subfamily 0
(2.2) Other Cys4
(2.3) Cys2 2
(2.4) Cys6
(2.5) Alternating composition
(2.6) WRKY
(4 ) β-Scaffold factors with minor groove contacts
(0) Other transcription factors
see also transcription factor/coregulator deficiencies
t
e
R e t r i e v e d f r o m " https://en.wikipedia.org/w/index.php?title=Carbohydrate-responsive_element-binding_protein&oldid=1223059699 " C a t e g o r i e s : ● G e n e s o n h u m a n c h r o m o s o m e 7 ● H u m a n c h r o m o s o m e 7 g e n e s t u b s H i d d e n c a t e g o r i e s : ● A r t i c l e s w i t h s h o r t d e s c r i p t i o n ● S h o r t d e s c r i p t i o n i s d i f f e r e n t f r o m W i k i d a t a ● A r t i c l e s n e e d i n g a d d i t i o n a l r e f e r e n c e s f r o m M a y 2 0 2 4 ● A l l a r t i c l e s n e e d i n g a d d i t i o n a l r e f e r e n c e s ● A l l s t u b a r t i c l e s
● T h i s p a g e w a s l a s t e d i t e d o n 9 M a y 2 0 2 4 , a t 1 6 : 4 8 ( U T C ) . ● T e x t i s a v a i l a b l e u n d e r t h e C r e a t i v e C o m m o n s A t t r i b u t i o n - S h a r e A l i k e L i c e n s e 4 . 0 ;
a d d i t i o n a l t e r m s m a y a p p l y . B y u s i n g t h i s s i t e , y o u a g r e e t o t h e T e r m s o f U s e a n d P r i v a c y P o l i c y . W i k i p e d i a ® i s a r e g i s t e r e d t r a d e m a r k o f t h e W i k i m e d i a F o u n d a t i o n , I n c . , a n o n - p r o f i t o r g a n i z a t i o n . ● P r i v a c y p o l i c y ● A b o u t W i k i p e d i a ● D i s c l a i m e r s ● C o n t a c t W i k i p e d i a ● C o d e o f C o n d u c t ● D e v e l o p e r s ● S t a t i s t i c s ● C o o k i e s t a t e m e n t ● M o b i l e v i e w
