The Scaffolding Protein RACK1 Interacts with Androgen Receptor and Promotes Cross-talk through a Protein Kinase C Signaling Pathway
| Autor: | Daniel M. Ozanne, David E. Neal, Craig N. Robson, Anastasia C. Rigas |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Transcriptional Activation
medicine.medical_specialty Indoles Time Factors Lactams Transcription Genetic Blotting Western Active Transport Cell Nucleus Biology Ligands Receptors for Activated C Kinase Biochemistry Transactivation Cell Line Tumor Two-Hybrid System Techniques Internal medicine LNCaP medicine Animals Humans Protein Isoforms RNA Messenger Molecular Biology Transcription factor Protein Kinase C Protein kinase C Reverse Transcriptase Polymerase Chain Reaction Cell Differentiation Cell Biology beta-Galactosidase Precipitin Tests Chromatin Protein Structure Tertiary Cell biology Androgen receptor Endocrinology Microscopy Fluorescence Nuclear receptor Receptors Androgen COS Cells Signal transduction Peptides Cell Division Gene Deletion Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 278:46087-46093 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m306219200 |
| Popis: | The androgen receptor (AR), a member of the nuclear hormone receptor superfamily, functions as a ligand-dependent transcription factor that regulates genes involved in cell proliferation and differentiation. Using a C-terminal region of the human AR in a yeast two-hybrid screen, we have identified RACK1 (receptor for activated C kinase-1) as an AR-interacting protein. In this report we found that RACK1, which was previously shown to be a protein kinase C (PKC)-anchoring protein that determines the localization of activated PKCbetaII isoform, facilitates ligand-independent AR nuclear translocation upon PKC activation by indolactam V. We also observed RACK1 to suppress ligand-dependent and -independent AR transactivation through PKC activation. In chromatin immunoprecipitation assays, we demonstrate a decrease in AR recruitment to the AR-responsive prostate-specific antigen (PSA) promoter following stimulation of PKC. Furthermore, prolonged exposure to indolactam V, a PKC activator, caused a reduction in PSA mRNA expression in prostate cancer LNCaP cells. Finally, we found PKC activation to have a repressive effect on AR and PSA protein expression in androgen-treated LNCaP cells. Our data suggest that RACK1 may function as a scaffold for the association and modification of AR by PKC enabling translocation of AR to the nucleus but rendering AR unable to activate transcription of its target genes. |
| Databáze: | OpenAIRE |
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