Stress-induced c-Jun-dependent Vitamin D Receptor (VDR) Activation Dissects the Non-classical VDR Pathway from the Classical VDR Activity
| Autor: | Qing-Ping Li, Rocky Pramanik, Guan Chen, Xiaomei Qi, Mathew Loesch, Nicole M. Pohl |
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| Rok vydání: | 2007 |
| Předmět: |
musculoskeletal diseases
Vitamin Chromatin Immunoprecipitation Programmed cell death Transcription Genetic Proto-Oncogene Proteins c-jun p38 mitogen-activated protein kinases Transfection Models Biological p38 Mitogen-Activated Protein Kinases Biochemistry Calcitriol receptor Mice chemistry.chemical_compound Cell Line Tumor Gene expression polycyclic compounds Animals Humans Phosphorylation Vitamin D Molecular Biology Transcription factor Cell Death digestive oral and skin physiology Stress induced c-jun Cell Biology chemistry NIH 3T3 Cells Cancer research Receptors Calcitriol lipids (amino acids peptides and proteins) |
| Zdroj: | Journal of Biological Chemistry. 282:1544-1551 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m604052200 |
| Popis: | Vitamin D receptor (VDR) is a ligand-dependent transcription factor that mediates vitamin D(3)-induced gene expression. Our previous work has established that stress MAPK signaling stimulates VDR expression (Qi, X., Pramank, R., Wang, J., Schultz, R. M., Maitra, R. K., Han, J., DeLuca, H. F., and Chen, G. (2002) J. Biol. Chem. 277, 25884-25892) and VDR inhibits cell death in response to p38 MAPK activation (Qi, X., Tang, J., Pramanik, R., Schultz, R. M., Shirasawa, S., Sasazuki, T., Han, J., and Chen, G. (2004) J. Biol. Chem. 279, 22138-22144). Here we show that c-Jun is essential for VDR expression and VDR in turn inhibits c-Jun-dependent cell death by non-classical mechanisms. In response to stress c-Jun is recruited to the Vdr promoter before VDR protein expression is induced. The necessary and sufficient role of c-Jun in VDR expression was established by the fact that c-Jun knock-out decreases VDR expression, whereas c-Jun restoration recovers its activity. Existence of the non-classical VDR pathway was suggested by a requirement of both c-Jun and VDR in stress-induced VDR activity and further demonstrated by VDR inhibiting c-Jun-dependent cell death independent of its classical transcriptional activity and independent of vitamin D(3). c-Jun is also required for vitamin D(3)-induced classical VDR transcriptional activity by a mechanism likely involving physical interactions between c-Jun and VDR proteins. These results together reveal a non-classical mechanism by which VDR acts as a c-Jun/AP-1 target gene to modify c-Jun activity in stress response through increased protein expression independent of classical transcriptional regulations. |
| Databáze: | OpenAIRE |
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