Faculty Collaboration Database

Stress-induced c-Jun-dependent Vitamin D receptor (VDR) activation dissects the non-classical VDR pathway from the classical VDR activity. J Biol Chem 2007 Jan 19;282(3):1544-51

Date

11/24/2006

Pubmed ID

17121851

DOI

10.1074/jbc.M604052200

Scopus ID

2-s2.0-33847265408 (requires institutional sign-in at Scopus site)   29 Citations

Abstract

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.

Author List

Li QP, Qi X, Pramanik R, Pohl NM, Loesch M, Chen G

Authors

Guan Chen MD, PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Xiao-Mei Qi MD Associate Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Death
Cell Line, Tumor
Chromatin Immunoprecipitation
Humans
Mice
Models, Biological
NIH 3T3 Cells
Phosphorylation
Proto-Oncogene Proteins c-jun
Receptors, Calcitriol
Transcription, Genetic
Transfection
Vitamin D
p38 Mitogen-Activated Protein Kinases