Ligand-Dependent Degradation of Retinoid X Receptors Does Not Require Transcriptional Activity or Coactivator Interactions
| Autor: | D L Osburn, H M Seidel, G Shao, Ira G. Schulman |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
Transcriptional Activation
Time Factors Transcription Genetic Protein Conformation Receptors Retinoic Acid Blotting Western Biology Retinoid X receptor Ligands Transfection Cell Line Coactivator Transcriptional regulation Animals Receptor Molecular Biology Transcription factor Ubiquitins Cells Cultured PELP-1 Transcriptional Regulation Cell Nucleus Receptors Thyroid Hormone Cell Biology Molecular biology Precipitin Tests Cell biology Protein Structure Tertiary Enzyme Activation Retinoid X Receptors embryonic structures Mutation Signal transduction Corepressor Dimerization Plasmids Protein Binding Signal Transduction Transcription Factors |
| Popis: | Cells utilize ubiquitin-mediated proteolysis to regulate the activity of numerous proteins involved in signal transduction, cell cycle control, and transcriptional regulation. For a number of transcription factors, there appears to be a direct correlation between transcriptional activity and protein instability, suggesting that cells use targeted destruction as one method to down-regulate or attenuate gene expression. In this report we demonstrate that retinoid X receptors (RXRs) which function as versatile mediators of nuclear hormone-dependent gene expression are marked for destruction upon binding agonist ligands. Interestingly, when RXR serves as a heterodimeric partner for retinoic acid (RAR) or thyroid hormone (TR) receptors, binding of agonists by RAR or TR leads to degradation of both the transcriptionally active RAR or TR subunits as well as the transcriptionally inactive RXR subunit. Furthermore, using a series of mutants in the ligand-dependent activation domain (activation function 2), we demonstrate that agonist-stimulated degradation of RXR does not require corepressor release, coactivator binding, or transcriptional activity. Taken together, the data suggest a model for targeted destruction of transcription factors based on structural or conformational signals as opposed to functional coupling with gene transcription. |
| Databáze: | OpenAIRE |
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