The role of heat shock protein 70 in vitamin D receptor function.
We previously demonstrated that the 1alpha,25-dihydroxyvitamin D(3) receptor (VDR) interacts with the constitutive heat shock protein, hsc70 in vitro, and with DnaK (Biochem. Biophys. Res. Commun. 260, 446-452, 1999). The biological significance of VDR-heat shock protein interactions, however, is unknown. To examine the role of such interactions in eukaryotic cells, we heterologously expressed VDR and RXRalpha together with a vitamin D-responsive reporter system in Saccharomyces cerevisiae and examined the consequences of heat shock protein 70 gene (SSA) deletion in these cells. We show that heterologously expressed VDR associates with the yeast cytosolic hsp70 protein, Ssa1p. Deletion of the SSA2, SSA3, and SSA4 genes and reduction of Ssa1p activity, reduces the intracellular concentrations of the VDR and its heterodimeric partner, RXRalpha and reduces the activity of a vitamin D-dependent gene. Hsp70-like chaperone proteins play a role in controlling concentrations of the VDR within the cell.
Lutz
W
W
Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Kohno
K
K
Kumar
R
R
D000251:Adenosine Triphosphatases; D015153:Blotting, Western; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics; D017353:Gene Deletion; D015870:Gene Expression; D017930:Genes, Reporter / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007163:Immunosorbent Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis / Q000235:genetics; D047488:Retinoid X Receptors; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D020539:Sequence Analysis, Protein; D013696:Temperature; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014170:Transformation, Genetic
D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D018167:Receptors, Calcitriol; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; C542288:SSA2 protein, S cerevisiae; C090869:SSA3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; C095973:SSA1 protein, S cerevisiae