Convergence of Peroxisome Proliferator-activated Receptor γ and Foxo1 Signaling Pathways*
By P. Dowell, Tamara C. Otto, S. Adi, M. Lane. Journal of Biological Chemistry, 2003
215 citations recorded by the source corpus.
The forkhead factor Foxo1 (or FKHR) was identified in a yeast two-hybrid screen as a peroxisome proliferator-activated receptor (PPAR) γ-interacting protein. Foxo1 antagonized PPARγ activity and vice versa indicating that these transcription factors functionally interact in a reciprocal antagonistic manner. One mechanism by which Foxo1 antagonizes PPARγ activity is through disruption of DNA binding as Foxo1 inhibited the DNA binding activity of a PPARγ/retinoid X receptor α heterodimeric complex. The Caenorhabditis elegans nuclear hormone receptor, DAF-12, interacted with the C. elegans forkhead factor, DAF-16, paralleling the interaction between PPARγ and Foxo1. daf-12 and daf-16 have been implicated in C. elegans insulin-like signaling pathways, and PPARγ and Foxo1 likewise have been linked to mammalian insulin signaling pathways. These results suggest a convergence of PPARγ and Foxo1 signaling that may play a role in insulin action and the insulinomimetic properties of PPARγ ligands. A more general convergence of nuclear hormone receptor and forkhead factor pathways may be important for multiple biological processes and this convergence may be evolutionarily conserved.
Subfields: Aging, Molecular Biology, Physiology
View Paper: https://www.semanticscholar.org/paper/f9a6aaff208f7697eaf56913f5d75b41405105d5
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In Aging
In Molecular Biology
- David M. Sabatini
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- A. Efeyan
- M. Birnbaum
- A. V. D. Heuvel
- David H. Gross
- Michael N. Hall
- M. Laplante
In Physiology
Citations in the corpus
- mTOR: from growth signal integration to cancer, diabetes and ageing (2010, background): “105 ) and to directly inhibit FOXO1, which usually antagonizes PPARγ activit”
- The role of FoxO in the regulation of metabolism (2008, background): “FoxO1 also binds to and represses the activity of the PPARg promoter as well as antagonizes PPARg’s ability to bind and transactivate target genes (Dowell et al., 2003; Armoni et al., 2006).”