Heat shock protein 27 mediates repression of androgen receptor function by protein kinase D1 in prostate cancer cells.
We have previously shown that protein kinase D1 (PKD1), charter member of PKD protein family, is downregulated in advanced prostate cancer (PC) and influences androgen receptor (AR) function in PC cells. Other independent studies showed that serine 82 residue in heat shock protein 27 (Hsp27) undergoes substrate phosphorylation by PKD1 and is associated with nuclear transport of AR resulting in increased AR transcriptional activity. In this study, we show that PKD1 interacts and phosphorylates Hsp27 at Ser82 in PC cells, which is mediated by p38-dependent mitogen-activated protein kinase pathway and is necessary for PKD1 repression of AR transcriptional activity and androgen-dependent proliferation of PC cells. The study provides first in vivo evidence that Hsp27 is a mediator of repression of AR function by PKD1 in PC cells, thereby linking the data in the published literature.
Hassan
S
S
Division of Urology, Department of Surgery, University of Massachusetts Medical School, Worcester, MA, USA.
Biswas
M H U
MH
Zhang
C
C
Du
C
C
Balaji
K C
KC
D001839:Bombesin / Q000494:pharmacology; D054713:Bryostatins / Q000494:pharmacology; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology*; D006360:Heat-Shock Proteins; D006801:Humans; D008297:Male; D018832:Molecular Chaperones; D046912:Multiprotein Complexes / Q000378:metabolism; D009496:Neurotensin / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms; D011485:Protein Binding; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D011944:Receptors, Androgen / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology
C410798:AR protein, human; D054713:Bryostatins; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D046912:Multiprotein Complexes; D011944:Receptors, Androgen; C046785:bryostatin 1; D009496:Neurotensin; C089212:protein kinase D; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; D001839:Bombesin