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Convergence of Peroxisome Proliferator-activated Receptor γ and Foxo1 Signaling Pathways

J. Biol. Chem., 14 November 2003
Vol. 278, Issue 46, p. 45485-45491
DOI: 10.1074/jbc.M309069200

Convergence of Peroxisome Proliferator-activated Receptor γ and Foxo1 Signaling Pathways

  1. Paul Dowell§,
  2. Tamara C. Otto,
  3. Saleh Adi and
  4. M. Daniel Lane
  1. Biological Chemistry and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
  1. § To whom correspondence should be addressed: Dept. of Biological Chemistry, WBSB 509, 725 N. Wolfe St., Baltimore, MD 21205. Tel.: 410-955-3975; Fax: 410-955-0903; E-mail: dowellp{at}


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.


  • 1 The abbreviations used are: PPAR, peroxisome proliferator-activated receptor; NHR, nuclear hormone receptor; RXR, retinoid X receptor; IGF, insulin-like growth factor; IGFBP, insulin-like growth factor-binding protein; HA, hemagglutinin; GST, glutathione S-transferase; ER, estrogen receptor; AR, androgen receptor; CBP, cAMP-responsive element-binding protein-binding protein.

  • 2 P. Dowell and M. D. Lane, unpublished results.

  • * This work was supported by Grants DK09894 and DK64934 (to P. D.) and DK38418 (to M. D. L.) from NIDDK, National Institutes of Health and by an Institutional Research Grant from Johns Hopkins University (to S. A.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Received August 15, 2003.


P. Dowell, T. C. Otto, S. Adi, and M. D. Lane, Convergence of Peroxisome Proliferator-activated Receptor γ and Foxo1 Signaling Pathways. J. Biol. Chem. 278, 45485-45491 (2003).

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