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Characterization of novel peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) isoform in human liver.

Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is a transcriptional coactivator that contributes to the regulation of numerous transcriptional programs including the hepatic response to fasting. Mechanisms at transcriptional and post-transcriptional levels allow PGC-1α to support distinct biological pathways. Here we describe a novel human liver-specific PGC-1α transcript that results from alternative promoter usage and is induced by FOXO1 as well as glucocorticoids and cAMP-response element-binding protein signaling but is not present in other mammals. Hepatic tissue levels of novel and wild-type transcripts were similar but were only moderately associated (p < 0.003). Novel mRNA levels were associated with a polymorphism located in its promoter region, whereas wild-type transcript levels were not. Furthermore, hepatic PCK1 mRNA levels exhibited stronger associations with the novel than with the wild-type transcript levels. Except for a deletion of 127 amino acids at the N terminus, the protein, termed L-PGC-1α, is identical to PGC-1α. L-PGC-1α was localized in the nucleus and showed coactivation properties that overlap with those of PGC-1α. Collectively, our data support a role of L-PGC-1α in gluconeogenesis, but functional differences predicted from the altered structure suggest that L-PGC-1α may have arisen to adapt PGC-1α to more complex metabolic pathways in humans.

Pubmed ID: 22009745

Authors

  • Felder TK
  • Soyal SM
  • Oberkofler H
  • Hahne P
  • Auer S
  • Weiss R
  • Gadermaier G
  • Miller K
  • Krempler F
  • Esterbauer H
  • Patsch W

Journal

The Journal of biological chemistry

Publication Data

December 16, 2011

Associated Grants

  • Agency: Austrian Science Fund FWF, Id: P 19893-B05

Mesh Terms

  • 8-Bromo Cyclic Adenosine Monophosphate
  • Animals
  • Blotting, Northern
  • Chromatin Immunoprecipitation
  • Dexamethasone
  • Female
  • Gene Expression
  • Genotype
  • Heat-Shock Proteins
  • Hep G2 Cells
  • Humans
  • Immunoblotting
  • In Vitro Techniques
  • Liver
  • Mice
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Protein Isoforms
  • RNA, Messenger
  • Rats
  • Transcription Factors