Heat shock protein 90{beta}: A novel mediator of vitamin D action
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Mineral Bioavailability Laboratory, 711 Washington Street, Boston, MA 02111 (United States)
- Thermal and Mountain Medicine Division, United States Army Research Institute of Environmental Medicine, 42 Kansas Street, Natick, MA 01760 (United States)
We investigated the role of Heat shock protein 90 (Hsp90) in vitamin D action in Caco-2 cells using geldanamycin (GA) to block Hsp90 function and RNA interference to reduce Hsp90{beta} expression. When cells were exposed to GA, vitamin D-mediated gene expression and transcriptional activity were inhibited by 69% and 54%, respectively. Gel shift analysis indicated that GA reduced vitamin D-mediated DNA binding activity of the vitamin D receptor (VDR). We tested the specific role of Hsp90{beta} by knocking down its expression with stably expressed short hairpin RNA. Vitamin D-induced gene expression and transcriptional activity were reduced by 90% and 80%, respectively, in Hsp90{beta}-deficient cells. Nuclear protein for VDR and RXR{alpha}, its heterodimer partner, were not reduced in Hsp90{beta}-deficient cells. These findings indicate that Hsp90{beta} is needed for optimal vitamin D responsiveness in the enterocyte and demonstrate a specific role for Hsp90{beta} in VDR signaling.
- OSTI ID:
- 21043655
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 367, Issue 3; Other Information: DOI: 10.1016/j.bbrc.2007.12.179; PII: S0006-291X(08)00011-9; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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