Functional interaction of human Cdc37 with the androgen receptor but not with the glucocorticoid receptor

Cdc37 is a molecular chaperone closely associated with the folding of prote in kinases. Results from studies using a yeast model system showed that it was also important for activation of the human androgen receptor (AR). Ease d on results from the yeast model system (Fliss, A. E., Fang, Y., Boschelli , F., and Caplan, A. J. (1991) Mol. Biol. Cell 8, 2501-2509), we initiated studies to address whether AR and Cdc37 interact with each other in animal cell systems. Our results show that Cdc37 binds to AR but not to glucocorti coid receptors (GR) synthesized in rabbit reticulocyte Lysates. This bindin g occurs via the ligand-binding domain of the AR. in a manner that is parti ally dependent on Hsp90 and the presence of hormone. Further studies using the yeast system showed that Cdc37 is not interchangeable with Hsp90, sugge sting that it functions at a distinct step in the activation pathway. Expre ssion of a dominant negative form of Cdc37 in animal cells down-regulates f ull-length AR but has very little effect on an AR truncation lacking the li gand-binding domain or full-length GR. These results reveal differences in the mechanisms by which AR and GR become active transcription factors and s trengthen the notion that Cdc37 has a wider range of polypeptide clients th an was realized previously.