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Aspects of the regulatory mechanisms of PPAR functions: Analysis of a bidirectional response element and regulation by sumoylation

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Abstract

Peroxisome proliferator-activated receptors (PPARs) constitute a subfamily of nuclear receptor superfamily. A wide variety of compounds including hypolipidemic agents, antidiabetic drugs, and long-chain fatty acids are the potential ligands of PPARs. To approach the regulatory mechanisms of PPARs, we studied on two subjects in this work. First, we identified a functional PPAR-binding site in the spacer region between the PEX11α and perilipin genes, which are arranged in tandem on the mouse genome. By gene reporter assays and in vivo as well as in vitro binding assays, we show that these genes are regulated tissue-selectively through this common binding site: The PEX11α gene is activated by PPARα in the liver, whereas the perilipin gene by PPARγ in the adipose tissue. As the second subject, we found that PPARγ2 is conjugated with small ubiquitin-related modifier (SUMO) at a specific lysine residue in the amino-terminal region. By site-directed mutagenesis combined with gene reporter assays and sumoylation analyses, we show that sumoylation represses the ligand-independent transactivating function carried by this region, and hence negatively regulates the whole transactivating competence of PPARγ2. In addition, phosphorylation at a specific site in the amino-terminal region represses the transactivation by PPARγ2 possibly through enhancing sumoylation.

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Authors and Affiliations

  1. Graduate School of Life Science, Himeji Institute of Technology, University of Hyogo, Kamigori, Hyogo, 678-1297, Japan

    Makoto Shimizu, Daisuke Yamashita, Tomohiro Yamaguchi, Fumiko Hirose & Takashi Osumi

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  1. Makoto Shimizu
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  2. Daisuke Yamashita
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  3. Tomohiro Yamaguchi
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  4. Fumiko Hirose
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  5. Takashi Osumi
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Correspondence to Takashi Osumi.

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MS and DY equally contributed to this work.

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Shimizu, M., Yamashita, D., Yamaguchi, T. et al. Aspects of the regulatory mechanisms of PPAR functions: Analysis of a bidirectional response element and regulation by sumoylation. Mol Cell Biochem 286, 33–42 (2006). https://doi.org/10.1007/s11010-005-9052-z

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  • DOI: https://doi.org/10.1007/s11010-005-9052-z

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