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 protein kinases. Results from studies using a yeast model system showed that it was also important for activation of the human androgen receptor (AR). Based on results from the yeast model system (Fliss, A. E., Fang, Y., Boschelli, F., and Caplan, A. J. (1997) 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 glucocorticoid receptors (GR) synthesized in rabbit reticulocyte lysates. This binding occurs via the ligand-binding domain of the AR in a manner that is partially dependent on Hsp90 and the presence of hormone. Further studies using the yeast system showed that Cdc37 is not interchangeable with Hsp90, suggesting that it functions at a distinct step in the activation pathway. Expression of a dominant negative form of Cdc37 in animal cells down-regulates full-length AR but has very little effect on an AR truncation lacking the ligand-binding domain or full-length GR. These results reveal differences in the mechanisms by which AR and GR become active transcription factors and strengthen the notion that Cdc37 has a wider range of polypeptide clients than was realized previously.
Rao
J
J
Department of Cell Biology and Anatomy , Mount Sinai School of Medicine, New York, New York 10029, USA.
Lee
P
P
Benzeno
S
S
Cardozo
C
C
Albertus
J
J
Robins
D M
DM
Caplan
A J
AJ
D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D018833:Chaperonins; D013196:Dihydrotestosterone / Q000494:pharmacology; D029721:Drosophila Proteins; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D013045:Species Specificity; D015533:Transcriptional Activation; D015003:Yeasts
C498362:CDC37 protein, human; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D018832:Molecular Chaperones; D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; D011994:Recombinant Proteins; D013196:Dihydrotestosterone; D018833:Chaperonins