Title: Differential splicing of the human peroxisome proliferator‐activated receptor, PPARβ/δ
Abstract: The peroxisome proliferator-activated receptor β (PPARβ/δ) is a ligand-activated nuclear receptor possessing important biological functions that include regulatory roles in cell proliferation, differentiation, survival, lipid metabolism, and development. In this study, we identified and characterized 2 novel human PPARβ mRNA splice variants that are expressed in liver tissues, possessing altered structures in exons 8 and 9, respectively. DNA sequence analysis indicated that the exon 8 variant contains a 90-base-pair in-frame deletion, while the exon 9 variant has a 116-base-pair deletion. The transfected constructs were stable in mammalian cells and distributed both in the nuclear and cytosolic compartments, similar to the wild type receptor. Co-transfection experiments were conducted in COS-1 cells to assess the transactivation potential of the variants on a consensus peroxisome proliferator response element driven reporter. We determined that the exon 8 deletion variant exhibited significantly less activity than wild type PPARβ, while the exon 9 variant possessed no detectable transactivation activity. Interaction with specific ligands and studies to determine dominant negative activities of the variants are in progress to determine the biological role of these variant receptors as potential differential regulators of PPARβ-driven genes.
Publication Year: 2007
Publication Date: 2007-04-01
Language: en
Type: article
Indexed In: ['crossref']
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