| First Author | Zheng Z | Year | 2002 |
| Journal | J Biol Chem | Volume | 277 |
| Issue | 52 | Pages | 50535-42 |
| PubMed ID | 12407098 | Mgi Jnum | J:80977 |
| Mgi Id | MGI:2447909 | Doi | 10.1074/jbc.M210526200 |
| Citation | Zheng Z, et al. (2002) Insulin-like Growth Factor-1 Increases Skeletal Muscle Dihydropyridine Receptor alpha 1S Transcriptional Activity by Acting on the cAMP-response Element-binding Protein Element of the Promoter Region. J Biol Chem 277(52):50535-42 |
| abstractText | Previous work from our laboratory has shown that insulin-like growth factor 1 (IGF-1) increases the expression of the skeletal muscle dihydropyridine receptor (DHPR) alpha(1) subunit by regulating DHPR alpha(1S) nuclear transcription. In this study, we investigated the mechanism by which IGF-1 enhances expression of the DHPR alpha(1S) gene. To this end, the promoter region of the mouse DHPR alpha(1S) gene was recently cloned and sequenced and various promoter deletion-luciferase reporter constructs were used. These constructs were transfected into C2C12 cells and IGF-1 effects were measured by recording luciferase activity. IGF-1 significantly enhanced DHPR alpha(1S) transcription in those constructs carrying cAMP-response element-binding protein (CREB) binding site but not in CREB core binding site mutants. Gel mobility shift assay using a double stranded oligonucleotide for the CREB site in the promoter region, and competition experiments with excess unlabeled or mutated promoter oligonucleotide, and unlabeled consensus CREB oligonucleotide demonstrated that IGF-1 induces CREB binding to the DHPR alpha(1S) promoter. IGF-1-mediated enhancement in charge movement was prevented by incubating the cells with antisense but not with sense oligonucleotides against CREB. These results support the conclusion that IGF-1 regulates DHPR alpha(1S) transcription in muscle cells by acting on the CREB element of the promoter. |
