title: Identification of a truncated alternative splicing variant of human PPARgamma1 that exhibits dominant negative activity.
abstract: We have identified a novel variant of human peroxisome proliferator-activated receptor gamma (hPPARgamma), 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 PPARgamma1 (PPARgamma1(tr)). Western blot analysis confirmed the presence of PPARgamma1(tr) in tumor-derived cell lines. Although PPARgamma1(tr) interfered with transcriptional activity of wild-type PPARgamma1 (PPARgamma1(wt)), activity could be rescued by cotransfection with a vector expressing p300. Overexpression of PPARgamma1(tr) protein in CHO cells greatly enhanced their proliferation and anchorage-independent colony growth on soft agar. These data demonstrate that PPARgamma1(tr) is an important physiologic isoform of PPARgamma that modulates cellular functions of PPARgamma1(wt).
authors.affiliation: Department of Pharmacology, Gyeongsang Institute of Health Science, College of Medicine, National University, Jinju, Republic of Korea.
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Im Sun
authors.initials: IS
authors.lastname: Woo
authors.forename: Eun Sil
authors.initials: ES
authors.lastname: Kang
authors.forename: So Young
authors.initials: SY
authors.lastname: Eun
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jae Heun
authors.initials: JH
authors.lastname: Lee
authors.forename: Ki Churl
authors.initials: KC
authors.lastname: Chang
authors.forename: Jin-Hoi
authors.initials: JH
authors.lastname: Kim
authors.forename: Han Geuk
authors.initials: HG
authors.lastname: Seo
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006224:Cricetinae; D014644:Genetic Variation / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D014162:Transfection
chemical_list: D047495:PPAR gamma