Journal article

A dominant-negative peroxisome proliferator-activated receptor gamma (PPAR gamma) mutant is a constitutive repressor and inhibits PPAR gamma-mediated adipogenesis

M Gurnell, JM Wentworth, M Agostini, M Adams, TN Collingwood, C Provenzano, PO Browne, O Rajanayagam, TP Burris, JW Schwabe, MA Lazar, VKK Chatterjee

Journal of Biological Chemistry | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2000

Abstract

The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) promotes adipocyte differentiation, exerts atherogenic and anti-inflammatory effects in monocyte/macrophages, and is believed to mediate the insulin-sensitizing action of antidiabetic thiazolidinedione ligands. As no complete PPARgamma antagonists have been described hitherto, we have constructed a dominant-negative mutant receptor to inhibit wild-type PPARgamma action. Highly conserved hydrophobic and charged residues (Leu(468) and Glu(471)) in helix 12 of the ligand-binding domain were mutated to alanine. This compound PPARgamma mutant retains ligand and DNA binding, but exhibits markedly reduced transactivat..

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University of Melbourne Researchers