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Atypical transcriptional regulators and cofactors of PPARγ

International Journal of Obesity volume 29, pages S10–S12 (2005)Cite this article

Abstract

Regulation of peroxisome proliferator-activated receptor gamma (PPARγ) activity is the result of several events. The first control level is the regulation of the expression of PPARγ. Examples of this regulation, during adipogenesis, is the transactivation of the PPARγ promoter by transcription factors of the classical pathway, such as C/EBPs or ADD1/SREBP1, but also newly identified factors, such as E2Fs. When preadipocytes re-enter the cell cycle, PPARγ expression is induced coincident with an increase in DNA synthesis, suggesting the involvement of the E2F family of cell cycle regulators. E2F1 induces PPARγ transcription during clonal expansion, whereas E2F4 represses PPARγ expression during terminal adipocyte differentiation. Hence, E2Fs represent the link between proliferative signaling pathways, triggering clonal expansion, and terminal adipocyte differentiation through regulation of PPARγ expression. A second regulatory level of PPARγ action is interaction with cofactors. We will focus our attention on the atypical PPARγ modulators. We have described an interaction between PPARγ and the retinoblastoma protein, RB, which is both dependent upon ligand binding by PPARγ and upon the phosphorylation status of RB. The interaction between PPARγ and RB decreases the transcriptional activity of PPARγ through recruitment of the histone deacetylase HDAC3. Inhibition of HDAC activity consequently results in a strong activation of PPARγ.

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Acknowledgements

Dr J Auwerx and the various members of the Fajas lab are acknowledged for support and discussion. The research in the laboratory of the author was supported by grants of INSERM (Avenir), Association pour la Recherche contre le Cancer, and Fondation pour la Recherche Médicale.

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  1. INSERM, U540, Equipe Avenir, Metabolism and Cancer Laboratory, Montpellier, France

    S Miard & L Fajas

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  1. S Miard
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Correspondence to L Fajas.

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Miard, S., Fajas, L. Atypical transcriptional regulators and cofactors of PPARγ. Int J Obes 29 (Suppl 1), S10–S12 (2005). https://doi.org/10.1038/sj.ijo.0802906

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