Carbohydrate-responsive element-binding protein

Source: Wikipedia, the free encyclopedia.
MLXIPL
Available structures
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl
UniProt
RefSeq (mRNA)

NM_032951
NM_032952
NM_032953
NM_032954
NM_032994

NM_021455
NM_001359237

RefSeq (protein)

NP_116569
NP_116570
NP_116571
NP_116572

NP_067430
NP_001346166

Location (UCSC)Chr 7: 73.59 – 73.62 MbChr 5: 135.12 – 135.17 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

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] 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

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]

Interactions

MLXIPL has been shown to

interact with MLX.[11]

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

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

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000009950 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000005373 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. S2CID 23530406
    .
  6. ^ a b c "Entrez Gene: MLXIPL MLX interacting protein-like".
  7. ^
    PMID 31275349
    .
  8. ^ .
  9. .
  10. .
  11. .

Further reading