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RNA Interference-based Investigation of the Function of Heat Shock Protein 27 during Corneal Epithelial Wound Healing
Published on: September 27, 2016
Heat shock protein 27 mediates repression of androgen receptor function by protein kinase D1 in prostate cancer cells
S Hassan1, M H U Biswas, C Zhang
1Division of Urology, Department of Surgery, University of Massachusetts Medical School, Worcester, MA, USA.
Abstract:
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.
Insights
Protein kinase D1 (PKD1) represses androgen receptor (AR) activity in prostate cancer (PC) by phosphorylating heat shock protein 27 (Hsp27). This interaction, mediated by the p38 pathway, inhibits PC cell proliferation.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Signaling
Background:
- Protein kinase D1 (PKD1) is downregulated in advanced prostate cancer (PC) and affects androgen receptor (AR) function.
- PKD1 phosphorylates heat shock protein 27 (Hsp27) at serine 82, influencing AR nuclear transport and transcriptional activity.
Purpose of the Study:
- To investigate the role of Hsp27 as a mediator in PKD1's repression of AR transcriptional activity and prostate cancer cell proliferation.
- To elucidate the signaling pathway involved in PKD1-mediated Hsp27 phosphorylation.
Main Methods:
- Co-immunoprecipitation assays to demonstrate interaction between PKD1 and Hsp27.
- Western blotting to detect Hsp27 phosphorylation at Ser82.
- Analysis of AR transcriptional activity and prostate cancer cell proliferation under various conditions.
Main Results:
- PKD1 directly interacts with and phosphorylates Hsp27 at Ser82 in prostate cancer cells.
- This phosphorylation is dependent on the p38-mitogen-activated protein kinase pathway.
- PKD1-mediated Hsp27 phosphorylation is essential for the repression of AR transcriptional activity and androgen-dependent prostate cancer cell proliferation.
Conclusions:
- Heat shock protein 27 (Hsp27) acts as a key mediator in the repression of androgen receptor (AR) function by protein kinase D1 (PKD1) in prostate cancer cells.
- The p38-dependent phosphorylation of Hsp27 by PKD1 is a critical mechanism controlling AR activity and prostate cancer cell growth.
- This study provides in vivo evidence linking PKD1, Hsp27, and AR signaling in prostate cancer progression.
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