Regulation of the mRNA-binding Protein AUF1 by Activation of the β -Adrenergic Receptor Signal Transduction Pathway
| Autor: | Michael R. Bristow, J. David Port, Gary Brewer, Aldo Pende, Wayne Minobe, John D. Bisognano, Christine T. DeMaria, Burns C. Blaxall, Jonathan A. Sherman, Kelli D. Tremmel |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Agonist
Ultraviolet Rays Immunoprecipitation medicine.drug_class Molecular Sequence Data Stimulation Biology Proto-Oncogene Mas Biochemistry law.invention GTP-Binding Proteins law Receptors Adrenergic beta medicine Humans Heterogeneous Nuclear Ribonucleoprotein D0 RNA Messenger Heterogeneous-Nuclear Ribonucleoprotein D Receptor Molecular Biology DNA Primers Heart Failure Messenger RNA Base Sequence Myocardium RNA-Binding Proteins Muscle Smooth Cell Biology Molecular biology Recombinant Proteins Gene Expression Regulation Cell culture Polyribosomes Recombinant DNA Signal transduction Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 271:8493-8501 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.271.14.8493 |
| Popis: | In both cell culture based model systems and in the failing human heart, beta-adrenergic receptors ( beta-AR) undergo agonist-mediated down-regulation. This decrease correlates closely with down-regulation of its mRNA, an effect regulated in part by changes in mRNA stability. Regulation of mRNA stability has been associated with mRNA-binding proteins that recognize A + U-rich elements within the 3'-untranslated regions of many mRNAs encoding proto-oncogene and cytokine mRNAs. We demonstrate here that the mRNA-binding protein, AUF1, is present in both human heart and in hamster DDT1-MF2 smooth muscle cells and that its abundance is regulated by beta-AR agonist stimulation. In human heart, AUF1 mRNA and protein was significantly increased in individuals with myocardial failure, a condition associated with increases in the beta-adrenergic receptor agonist norepinephrine. In the same hearts, there was a significant decrease (approximately 50%) in the abundance of beta1-AR mRNA and protein. In DDT1-MF2 cells, where agonist-mediated destabilization of beta2-AR mRNA was first described, exposure to beta-AR agonist resulted in a significant increase in AUF1 mRNA and protein (approximately 100%). Conversely, agonist exposure significantly decreased (approximately 40%) beta2-adrenergic receptor mRNA abundance. Last, we demonstrate that AUF1 can be immunoprecipitated from polysome-derived proteins following UV cross-linking to the 3'-untranslated region of the human beta1-AR mRNA and that purified, recombinant p37AUF1 protein also binds to beta1-AR 3'-untranslated region mRNA. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|