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Published on: June 3, 2016

Convergence of peroxisome proliferator-activated receptor gamma and Foxo1 signaling pathways

Paul Dowell1, Tamara C Otto, Saleh Adi

  • 1Biological Chemistry and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. dowellp@jhmi.edu

The Journal of Biological Chemistry
|September 11, 2003
PubMed

Insights

The forkhead factor Foxo1 antagonizes PPARgamma activity, impacting insulin signaling. This interaction, conserved across species, suggests a convergence of nuclear hormone receptor and forkhead factor pathways in biological processes.

Area of Science:

  • Molecular Biology
  • Genetics
  • Endocrinology

Background:

  • The forkhead factor Foxo1 (FKHR) interacts with peroxisome proliferator-activated receptor gamma (PPARgamma).
  • Foxo1 and PPARgamma exhibit reciprocal antagonism, suggesting functional interaction.
  • Both factors are linked to mammalian insulin signaling pathways.

Purpose of the Study:

  • To investigate the functional interaction between Foxo1 and PPARgamma.
  • To explore the role of this interaction in insulin signaling.
  • To examine the evolutionary conservation of nuclear hormone receptor and forkhead factor pathways.

Main Methods:

  • Yeast two-hybrid screening to identify interacting proteins.
  • Assays to assess DNA binding activity of transcription factor complexes.
  • Comparative analysis of homologous interactions in Caenorhabditis elegans.

Main Results:

  • Foxo1 was identified as a PPARgamma-interacting protein.
  • Foxo1 antagonizes PPARgamma activity by disrupting its DNA binding.
  • A similar interaction between DAF-12 (nuclear hormone receptor) and DAF-16 (forkhead factor) was observed in C. elegans.
  • Both interactions are implicated in insulin signaling pathways.

Conclusions:

  • Foxo1 and PPARgamma signaling converge, potentially influencing insulin action.
  • This convergence may explain the insulinomimetic properties of PPARgamma ligands.
  • A broader convergence between nuclear hormone receptor and forkhead factor pathways is likely conserved and important for various biological processes.

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