Association of prokaryotic and eukaryotic chaperone proteins with the human 1alpha,25-dihydroxyvitamin D(3) receptor.

Steroid hormone receptors (SHR) form complexes with heat shock proteins (hsps). The 1alpha,25-dihydroxyvitamin D(3) receptor (VDR) has not been previously shown to interact with hsps. During expression and purification of VDR-glutathione S-transferase (VDR-GST) fusion proteins encompassing full-length, DNA, and ligand-binding domains of the VDR (FL-VDR, DBD-VDR, and LBD-VDR), we observed binding of bacterial hsps with VDR-GST constructs. All VDR constructs bound DnaK in amounts greater than GST alone and bound smaller amounts of DnaJ or GrpE. GroEL bound only to FL-VDR. GroES did not bind to VDR. When VDR-GST constructs were incubated with a reticulocyte lysate system that has been used previously to examine SHR-hsp interactions, eukaryotic hsc70 was detected bound to FL-VDR and DBD-VDR. Binding of hsp90 to VDR was not detected. However, geldanamycin, an hsp90 inhibitor, reduced 1alpha,25-dihydroxyvitamin D(3)-mediated gene activation in osteoblasts. Our data show that the bacterial and eukaryotic hsps associate with the VDR and might be involved in VDR function. Copyright 1999 Academic Press.