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 (hPPARγ), 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 PPARγ1 (PPARγ1tr). Western blot analysis confirmed the presence of PPARγ1tr in tumor-derived cell lines. Although PPARγ1tr interfered with transcriptional activity of wild-type PPARγ1 (PPARγ1wt), activity could be rescued by cotransfection with a vector expressing p300. Overexpression of PPARγ1tr protein in CHO cells greatly enhanced their proliferation and anchorage-independent colony growth on soft agar. These data demonstrate that PPARγ1tr is an important physiologic isoform of PPARγ that modulates cellular functions of PPARγ1wt.