Identification of a truncated alternative splicing variant of human PPARγ1 that exhibits dominant negative activity

We have identified a novel variant of human peroxisome proliferator-activated receptor gamma (hPPAR gamma), derived from insertion of a novel exon 3'. Insertion leads to the introduction of a premature stop codon, resulting in the formation of a truncated splice variant of PPAR gamma 1 (PPAR gamma 1(tr)). Western blot analysis confirmed the presence of PPAR gamma 1(tr) in tumor-derived cell lines. Although PPAR gamma 1(tr) interfered with transcriptional activity of wild-type PPAR gamma 1 (PPAR gamma 1(wt)), activity could be rescued by cotransfection with a vector expressing p300. Overexpression of PPAR gamma 1(tr) protein in CHO cells greatly enhanced their proliferation and anchorage-independent colony growth on soft agar. These data demonstrate that PPAR gamma 1(tr) is an important physiologic isoform of PPAR gamma that modulates cellular functions of PPAR gamma 1(wt). (c) 2006 Elsevier Inc. All rights reserved.