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Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily that modulate target gene expression in response to fatty acid ligands. Their regulation by post-translational modifications has been reported but is poorly understood. | ễFEBS Journal Expression level and agonist-binding affect the turnover ubiquitination and complex formation of peroxisome proliferator activated receptor b Markus Rieck Lena Wedeken Sabine Muller-Brusselbach Wolfgang Meissner and Rolf Muller Institute of Molecular Biology and Tumor Research IMT Philipps University Marburg Germany Keywords GW501516 polyubiquitination PPARb ubiquitin Correspondence R. Muller Institute of Molecular Biology and Tumor Research IMT Philipps University Emil-Mannkopff-Strasse 2 35032 Marburg Germany E-mail rmueller@imt.uni-marburg.de These authors contributed equally to this work Received 4 July 2007 revised 30 July 2007 accepted 1 August 2007 doi 10.1111 j.1742-4658.2007.06037.x Peroxisome proliferator-activated receptors PPARs are members of the nuclear hormone receptor superfamily that modulate target gene expression in response to fatty acid ligands. Their regulation by post-translational modifications has been reported but is poorly understood. In the present study we investigated whether ligand binding affects the turnover and ubiquitination of the PPARb subtype also known as PPARỖ . Our data show that the ubiquitination and degradation of PPARb is not significantly influenced by the synthetic agonist GW501516 under conditions of moderate PPARb expression. By contrast the overexpression of PPARb dramatically enhanced its degradation concomitant with its polyubiquitination and the formation of high molecular mass complexes containing multiple presumably oligomerized PPARb molecules that lacked stoichiometical amounts of the obligatory PPARb dimerization partner retinoid X receptor. The formation of these apparently aberrant complexes as well as the ubiquitination and destabilization of PPARb were strongly inhibited by GW501516. Our findings suggest that PPARb is subject to complex post-translational regulatory mechanisms that partly may serve to safeguard the cell against deregulated PPARb expression. Furthermore our data have .
