Abstract. The YDJI (yeast dnaJ) gene was isolated from a yeast expression library using antisera made against a yeast nuclear sub-fraction termed the matrix lamina pore complex . The predicted open reading frame displays a 32% identity with the sequence of the Escherichia coli heat shock protein dnaJ. Localization of YDJI protein (YDJlp) by indirect immunofluorescence reveals it to be concentrated in a perinuclear ring as well as in the cytoplasm . YDJlp cofractionates with
The regulation of human androgen receptor (AR) by the molecular chaperone Hsp90 was investigated using the yeast Saccharomyces cerevisiae as a model system. These studies were performed in strains expressing a conditional temperature-sensitive mutant allele of the hsp82 gene, which encodes Hsp90 protein. At the restrictive temperature in the mutant, there is a decrease in hormone-dependent transactivation by the AR, although steady state levels of AR protein are unchanged. Quantitative hormone binding studies at the permissive temperature revealed the presence of both high affinity and low affinity hormone binding states. At the restrictive temperature in the hsp82 mutant, the high affinity state was abolished, and only the low affinity state was observed. The change in hormone binding affinity was further investigated by a competition assay with the anti-androgen hydroxyflutamide. Under permissive conditions, hydroxyflutamide competes poorly for the synthetic androgen R1881, but under restrictive conditions in the hsp82 mutant strain, hydroxyflutamide was shown to be a potent competitive inhibitor. Our findings indicate that Hsp90 participates in the activation process by maintaining apoAR in a high affinity ligand binding conformation which is important for efficient response to hormone.
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