Skip to main content

Estrogen-related receptors stimulate pyruvate dehydrogenase kinase isoform 4 gene expression.

Publication ,  Journal Article
Zhang, Y; Ma, K; Sadana, P; Chowdhury, F; Gaillard, S; Wang, F; McDonnell, DP; Unterman, TG; Elam, MB; Park, EA
Published in: J Biol Chem
December 29, 2006

The pyruvate dehydrogenase complex (PDC) catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria and is a key regulatory enzyme in the oxidation of glucose to acetyl-CoA. Phosphorylation of PDC by the pyruvate dehydrogenase kinases (PDK2 and PDK4) inhibits PDC activity. Expression of the PDK genes is elevated in diabetes, leading to the decreased oxidation of pyruvate to acetyl-CoA. In these studies we have investigated the transcriptional regulation of the PDK4 gene by the estrogen-related receptors (ERRalpha and ERRgamma). The ERRs are orphan nuclear receptors whose physiological roles include the induction of fatty acid oxidation in heart and muscle. Previously, we found that the peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the expression of PDK4. Here we report that ERRalpha and ERRgamma stimulate the PDK4 gene in hepatoma cells, suggesting a novel role for ERRs in controlling pyruvate metabolism. In addition, both ERR isoforms recruit PGC-1alpha to the PDK4 promoter. Insulin, which decreases the expression of the PDK4 gene, inhibits the induction of PDK4 by ERRalpha and ERRgamma. The forkhead transcription factor (FoxO1) binds the PDK4 gene and contributes to the induction of PDK4 by ERRs and PGC-1alpha. Insulin suppresses PDK4 expression in part through the dissociation of FoxO1 and PGC-1alpha from the PDK4 promoter. Our data demonstrate a key role for the ERRs in the induction of hepatic PDK4 gene expression.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

December 29, 2006

Volume

281

Issue

52

Start / End Page

39897 / 39906

Location

United States

Related Subject Headings

  • Transcription Factors
  • Receptors, Estrogen
  • Receptors, Cytoplasmic and Nuclear
  • Rats
  • RNA-Binding Proteins
  • Pyruvates
  • Protein Serine-Threonine Kinases
  • Protein Kinases
  • Protein Binding
  • Promoter Regions, Genetic
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhang, Y., Ma, K., Sadana, P., Chowdhury, F., Gaillard, S., Wang, F., … Park, E. A. (2006). Estrogen-related receptors stimulate pyruvate dehydrogenase kinase isoform 4 gene expression. J Biol Chem, 281(52), 39897–39906. https://doi.org/10.1074/jbc.M608657200
Zhang, Yi, Ke Ma, Prabodh Sadana, Farhana Chowdhury, Stephanie Gaillard, Fang Wang, Donald P. McDonnell, Terry G. Unterman, Marshall B. Elam, and Edwards A. Park. “Estrogen-related receptors stimulate pyruvate dehydrogenase kinase isoform 4 gene expression.J Biol Chem 281, no. 52 (December 29, 2006): 39897–906. https://doi.org/10.1074/jbc.M608657200.
Zhang Y, Ma K, Sadana P, Chowdhury F, Gaillard S, Wang F, et al. Estrogen-related receptors stimulate pyruvate dehydrogenase kinase isoform 4 gene expression. J Biol Chem. 2006 Dec 29;281(52):39897–906.
Zhang, Yi, et al. “Estrogen-related receptors stimulate pyruvate dehydrogenase kinase isoform 4 gene expression.J Biol Chem, vol. 281, no. 52, Dec. 2006, pp. 39897–906. Pubmed, doi:10.1074/jbc.M608657200.
Zhang Y, Ma K, Sadana P, Chowdhury F, Gaillard S, Wang F, McDonnell DP, Unterman TG, Elam MB, Park EA. Estrogen-related receptors stimulate pyruvate dehydrogenase kinase isoform 4 gene expression. J Biol Chem. 2006 Dec 29;281(52):39897–39906.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

December 29, 2006

Volume

281

Issue

52

Start / End Page

39897 / 39906

Location

United States

Related Subject Headings

  • Transcription Factors
  • Receptors, Estrogen
  • Receptors, Cytoplasmic and Nuclear
  • Rats
  • RNA-Binding Proteins
  • Pyruvates
  • Protein Serine-Threonine Kinases
  • Protein Kinases
  • Protein Binding
  • Promoter Regions, Genetic