Re-evaluating the FOXO1–PGC-1α connection (original) (raw)

Gluconeogenesis

Nature volume 443, pages E10–E11 (2006)Cite this article

Abstract

Arising from: P. Puigserver et al. Nature 423, 550–555 (2003).

Increased expression of the gene encoding the enzyme glucose-6-phosphatase (G6Pase) contributes to the increased production of glucose by the liver that occurs in individuals with diabetes. Puigserver et al.1 show that the transcription factor FOXO1 and the transcriptional co-activator PGC-1α act synergistically to stimulate the expression of genes in the gluconeogenesis pathway and propose that PGC-1α acts, in part, directly through FOXO1. Here we show that FOXO1 is neither required nor sufficient for the stimulation of G6Pase–luciferase fusion gene expression by PGC-1α. Our results indicate that the transcriptional interaction between FOXO1 and PGC-1α is indirect.

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Figure 1: Mutation of FOXO1 binding sites (IRSs 1, 2, 3 and FKHR B and C motifs) in the promoter of the gene encoding glucose-6-phosphatase (G6Pase) abolishes the induction of G6Pase fusion-gene expression by FOXO1 but not by PGC-1α.

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Authors and Affiliations

  1. Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, 37232, Tennessee, USA
    Marcia M. Schilling, James K. Oeser, Jared N. Boustead, Brian P. Flemming & Richard M. O'Brien

Authors

  1. Marcia M. Schilling
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  2. James K. Oeser
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  3. Jared N. Boustead
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  4. Brian P. Flemming
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  5. Richard M. O'Brien
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Schilling, M., Oeser, J., Boustead, J. et al. Re-evaluating the FOXO1–PGC-1α connection.Nature 443, E10–E11 (2006). https://doi.org/10.1038/nature05288

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