Open AccesscGMP-Dependent Protein Kinase Iβ Interacts with p44/WDR77 to Regulate Androgen Receptor-Driven Gene Expression
Author(s) -
Liran Zhou,
Keiko Hosohata,
Shen Gao,
Zhifeng Gu,
Zhengxin Wang
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0063119
Subject(s) - androgen receptor , signal transduction , prostate cancer , microbiology and biotechnology , biology , kinase , androgen , cancer research , regulation of gene expression , protein kinase a , endocrinology , chemistry , medicine , gene , cancer , biochemistry , genetics , hormone
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.