Cloning and characterization of a functional peroxisome proliferator activator receptor-gamma-responsive element in the promoter of the CAP gene
| Autor: | Alan R. Saltiel, Neel Chokshi, Baumann Christian Andrew, Vered Ribon |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Receptors
Retinoic Acid Response element Molecular Sequence Data Retinoic acid Peroxisome proliferator-activated receptor Receptors Cytoplasmic and Nuclear Retinoid X receptor Biochemistry chemistry.chemical_compound Mice Animals Humans Cloning Molecular Promoter Regions Genetic Molecular Biology Transcription factor chemistry.chemical_classification Base Sequence Activator (genetics) Tyrosine phosphorylation Cell Biology 3T3 Cells DNA Cell biology Cytoskeletal Proteins Retinoid X Receptors chemistry Cancer research Phosphorylation Dimerization Protein Binding Transcription Factors |
| Zdroj: | The Journal of biological chemistry. 275(13) |
| ISSN: | 0021-9258 |
| Popis: | c-Cbl-associating protein (CAP) is a multifunctional signaling protein that interacts with c-Cbl, facilitating the tyrosine phosphorylation of c-Cbl in response to insulin. In 3T3-L1 adipocytes and diabetic rodents, CAP gene expression is stimulated by activators of peroxisome proliferator activator receptor gamma (PPARgamma), such as thiazolidinediones (TZDs), resulting in increased insulin-stimulated c-Cbl phosphorylation. Sequence analysis of 2.5 kilobases of the 5'-flanking region of the CAP gene reveals a predicted peroxisome proliferator response element (PPRE) from -1085 to -1097. The isolated promoter was functional in 3T3 fibroblasts and adipocytes. Co-transfection of the CAP promoter with PPARgamma and retinoic acid X receptor alpha caused fold stimulation of promoter activity. The TZD rosiglitazone produced an additional 2-3-fold stimulation of the promoter. Deletion of the predicted PPRE from the CAP promoter abolished its ability to respond to rosiglitazone. Gel shift analysis of the putative PPARgamma site demonstrates direct binding of PPAR/retinoid X receptor heterodimers to the PPRE in the CAP gene. These data demonstrate that TZDs directly stimulate transcription of the CAP gene through activation of PPARgamma. |
| Databáze: | OpenAIRE |
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