Identification of a truncated alternative splicing variant of human PPARgamma1 that exhibits dominant negative activity.
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).
Kim
Hyo Jung
HJ
Department of Pharmacology, Gyeongsang Institute of Health Science, College of Medicine, National University, Jinju, Republic of Korea.
Woo
Im Sun
IS
Kang
Eun Sil
ES
Eun
So Young
SY
Kim
Hye Jung
HJ
Lee
Jae Heun
JH
Chang
Ki Churl
KC
Kim
Jin-Hoi
JH
Seo
Han Geuk
HG
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
D047495:PPAR gamma