Glucose-6-phosphate mediates activation of the carbohydrate responsive binding protein (ChREBP)

Ming V. Li, Weiqin Chen, Romain N. Harmancey, Alli M. Nuotio-Antar, Minako Imamura, Pradip Saha, Heinrich Taegtmeyer, Lawrence Chan

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Carbohydrate response element binding protein (ChREBP) is a Mondo family transcription factor that activates a number of glycolytic and lipogenic genes in response to glucose stimulation. We have previously reported that high glucose can activate the transcriptional activity of ChREBP independent of the protein phosphatase 2A (PP2A)-mediated increase in nuclear entry and DNA binding. Here, we found that formation of glucose-6-phosphate (G-6-P) is essential for glucose activation of ChREBP. The glucose response of GAL4-ChREBP is attenuated by d-mannoheptulose, a potent hexokinase inhibitor, as well as over-expression of glucose-6-phosphatase (G6Pase); kinetics of activation of GAL4-ChREBP can be modified by exogenously expressed GCK. Further metabolism of G-6-P through the two major glucose metabolic pathways, glycolysis and pentose-phosphate pathway, is not required for activation of ChREBP; over-expression of glucose-6-phosphate dehydrogenase (G6PD) diminishes, whereas RNAi knockdown of the enzyme enhances, the glucose response of GAL4-ChREBP, respectively. Moreover, the glucose analogue 2-deoxyglucose (2-DG), which is phosphorylated by hexokinase, but not further metabolized, effectively upregulates the transcription activity of ChREBP. In addition, over-expression of phosphofructokinase (PFK) 1 and 2, synergistically diminishes the glucose response of GAL4-ChREBP. These multiple lines of evidence support the conclusion that G-6-P mediates the activation of ChREBP.

Original languageEnglish (US)
Pages (from-to)395-400
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume395
Issue number3
DOIs
StatePublished - May 7 2010
Externally publishedYes

Fingerprint

Glucose-6-Phosphate
Carrier Proteins
Chemical activation
Carbohydrates
Glucose
Hexokinase
Mannoheptulose
Phosphofructokinase-2
Phosphofructokinase-1
saccharide-binding proteins
Protein Phosphatase 2
Pentose Phosphate Pathway
Glucose-6-Phosphatase
Pentoses
Glucosephosphate Dehydrogenase
Deoxyglucose
Response Elements
Glycolysis
RNA Interference
Metabolic Networks and Pathways

Keywords

  • Carbohydrate response element binding protein (ChREBP)
  • Glucose-6-phosphate (G-6-P)
  • Transcriptional activation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Glucose-6-phosphate mediates activation of the carbohydrate responsive binding protein (ChREBP). / Li, Ming V.; Chen, Weiqin; Harmancey, Romain N.; Nuotio-Antar, Alli M.; Imamura, Minako; Saha, Pradip; Taegtmeyer, Heinrich; Chan, Lawrence.

In: Biochemical and Biophysical Research Communications, Vol. 395, No. 3, 07.05.2010, p. 395-400.

Research output: Contribution to journalArticle

Li, Ming V. ; Chen, Weiqin ; Harmancey, Romain N. ; Nuotio-Antar, Alli M. ; Imamura, Minako ; Saha, Pradip ; Taegtmeyer, Heinrich ; Chan, Lawrence. / Glucose-6-phosphate mediates activation of the carbohydrate responsive binding protein (ChREBP). In: Biochemical and Biophysical Research Communications. 2010 ; Vol. 395, No. 3. pp. 395-400.
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