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Mol. Cell. Biol. 22 (14): 5114-5127

Copyright © 2002 by the American Society for Microbiology. All rights reserved.

Selective Cooperation between Fatty Acid Binding Proteins and Peroxisome Proliferator-Activated Receptors in Regulating Transcription

Nguan-Soon Tan,1 Natacha S. Shaw,2 Nicolas Vinckenbosch,1,2 Peng Liu,2 Rubina Yasmin,1 Béatrice Desvergne,1 Walter Wahli,1 and Noa Noy2*

Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853,2 Institut de Biologie Animale, Université de Lausanne, CH-1015 Lausanne, Switzerland1

Received for publication 24 July 2001. Revision received 5 September 2001.

Abstract: Lipophilic compounds such as retinoic acid and long-chain fatty acids regulate gene transcription by activating nuclear receptors such as retinoic acid receptors (RARs) and peroxisome proliferator-activated receptors (PPARs). These compounds also bind in cells to members of the family of intracellular lipid binding proteins, which includes cellular retinoic acid-binding proteins (CRABPs) and fatty acid binding proteins (FABPs). We previously reported that CRABP-II enhances the transcriptional activity of RAR by directly targeting retinoic acid to the receptor. Here, potential functional cooperation between FABPs and PPARs in regulating the transcriptional activities of their common ligands was investigated. We show that adipocyte FABP and keratinocyte FABP (A-FABP and K-FABP, respectively) selectively enhance the activities of PPAR{gamma} and PPARß, respectively, and that these FABPs massively relocate to the nucleus in response to selective ligands for the PPAR isotype which they activate. We show further that A-FABP and K-FABP interact directly with PPAR{gamma} and PPARß and that they do so in a receptor- and ligand-selective manner. Finally, the data demonstrate that the presence of high levels of K-FABP in keratinocytes is essential for PPARß-mediated induction of differentiation of these cells. Taken together, the data establish that A-FABP and K-FABP govern the transcriptional activities of their ligands by targeting them to cognate PPARs in the nucleus, thereby enabling PPARs to exert their biological functions.

* Corresponding author. Mailing address: 225 Savage Hall, Cornell University, Ithaca, NY 14853. Phone: (607) 255-2490. Fax: (607) 255-1033. E-mail: nn14{at}cornell.edu.

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