cGMP-dependent protein kinase Iβ interacts with p44/WDR77 to regulate androgen receptor-driven gene expression.

The androgen receptor (AR) pathway plays critical roles in controlling differentiation and proliferation of prostate epithelial cells. We previously identified a novel AR cofactor, p44/WDR77, which specifically enhances AR transcriptional activity in the prostate gland and prostate cancer. To further elucidate p44/WDR77's role in the AR signaling pathway, we conducted ...
a yeast two-hybrid screening and identified cGMP-dependent protein kinase (PKG) as a p44/WDR77-interacting protein. Further investigation by lusiferase assay and kinase assay demonstrated that PKG-Iβ physically interacted with and phosphorylated both p44 and AR and enhanced AR transactivity in synergy with p44 in an androgen- and cGMP-dependent manner. Furthermore, PKG1β expression promoted p44/WDR77 nuclear translocation and inhibited prostate cancer cell growth via G1 cell cycle arrest. Our findings characterize PKG as a novel regulator of AR-mediated transcription by enhancing AR cofactor p44/WDR77's function, which provide a novel mechanism for the growth regulation of prostate cancer cells by the androgen signaling.
Mesh Terms:
Animals, Cell Cycle, Cell Line, Tumor, Cell Nucleus, Cell Proliferation, Cyclic GMP-Dependent Protein Kinase Type I, Gene Expression Regulation, Neoplastic, Humans, Male, Mice, Inbred C57BL, Peptide Fragments, Phosphorylation, Promoter Regions, Genetic, Prostate, Protein Binding, Protein Structure, Tertiary, Protein Transport, Receptors, Androgen, Receptors, Glucocorticoid, Receptors, Progesterone, Transcription Factors, Transcription, Genetic, Tumor Suppressor Protein p53, Two-Hybrid System Techniques
PLoS ONE
Date: Jun. 12, 2013
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