ZIP kinase plays a crucial role in androgen receptor-mediated transcription
| Autor: | Peter Leister, Andrea Felten, Karl-Heinz Scheidtmann, A I Chasan |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Transcriptional Activation
Cancer Research Apoptosis antagonizing transcription factor Transcription Genetic Biology Mitogen-activated protein kinase kinase Transactivation Genetics Animals Humans Promoter Regions Genetic Molecular Biology Transcription factor Cells Cultured General transcription factor Rats Repressor Proteins Androgen receptor Death-Associated Protein Kinases Enhancer Elements Genetic Receptors Androgen Calcium-Calmodulin-Dependent Protein Kinases Cancer research Cyclin-dependent kinase 9 Apoptosis Regulatory Proteins Chromatin immunoprecipitation Protein Binding Transcription Factors |
| Zdroj: | Oncogene. 27:3292-3300 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1210995 |
| Popis: | The androgen receptor (AR) is a ligand-dependent transcription factor that plays a crucial role in the development and homeostasis of the prostate and in prostate cancer. The transcriptional activity of AR is mediated by interaction with multiple co-activators, which serve in chromatin modification or remodeling, or provide a link between specific and general transcription factors. We have identified zipper interacting protein (ZIP) kinase as a novel transcriptional co-activator of the AR. ZIP kinase enhanced expression of AR-responsive promotor/luciferase reporter constructs in a hormone- and kinase-dependent manner. Similar results were obtained for glucocorticoid receptor but not for progesterone receptor and estrogen receptor. Following hormone treatment, AR and ZIP kinase formed physical complexes and associated with the promoter and enhancer of the prostate-specific antigen gene, as revealed by chromatin immunoprecipitation. Strikingly, depletion of ZIP kinase by siRNA led to significant reduction of AR-mediated transactivation. The interaction of ZIP kinase with AR seems to be mediated in part by apoptosis antagonizing transcription factor and in part by direct binding. Interestingly, AR was not phosphorylated by ZIP kinase in vitro, suggesting that it phosphorylates other co-activators or chromatin proteins. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|