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 furthe...

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Autores principales:	Liran Zhou, Keiko Hosohata, Shen Gao, Zhongping Gu, Zhengxin Wang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3152a455291f40349327b011ee1da05f
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spelling	oai:doaj.org-article:3152a455291f40349327b011ee1da05f2021-11-18T07:43:18ZcGMP-dependent protein kinase Iβ interacts with p44/WDR77 to regulate androgen receptor-driven gene expression.1932-620310.1371/journal.pone.0063119https://doaj.org/article/3152a455291f40349327b011ee1da05f2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23755100/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Liran ZhouKeiko HosohataShen GaoZhongping GuZhengxin WangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e63119 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Liran Zhou Keiko Hosohata Shen Gao Zhongping Gu Zhengxin Wang cGMP-dependent protein kinase Iβ interacts with p44/WDR77 to regulate androgen receptor-driven gene expression.
description	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.
format	article
author	Liran Zhou Keiko Hosohata Shen Gao Zhongping Gu Zhengxin Wang
author_facet	Liran Zhou Keiko Hosohata Shen Gao Zhongping Gu Zhengxin Wang
author_sort	Liran Zhou
title	cGMP-dependent protein kinase Iβ interacts with p44/WDR77 to regulate androgen receptor-driven gene expression.
title_short	cGMP-dependent protein kinase Iβ interacts with p44/WDR77 to regulate androgen receptor-driven gene expression.
title_full	cGMP-dependent protein kinase Iβ interacts with p44/WDR77 to regulate androgen receptor-driven gene expression.
title_fullStr	cGMP-dependent protein kinase Iβ interacts with p44/WDR77 to regulate androgen receptor-driven gene expression.
title_full_unstemmed	cGMP-dependent protein kinase Iβ interacts with p44/WDR77 to regulate androgen receptor-driven gene expression.
title_sort	cgmp-dependent protein kinase iβ interacts with p44/wdr77 to regulate androgen receptor-driven gene expression.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/3152a455291f40349327b011ee1da05f
work_keys_str_mv	AT liranzhou cgmpdependentproteinkinaseibinteractswithp44wdr77toregulateandrogenreceptordrivengeneexpression AT keikohosohata cgmpdependentproteinkinaseibinteractswithp44wdr77toregulateandrogenreceptordrivengeneexpression AT shengao cgmpdependentproteinkinaseibinteractswithp44wdr77toregulateandrogenreceptordrivengeneexpression AT zhongpinggu cgmpdependentproteinkinaseibinteractswithp44wdr77toregulateandrogenreceptordrivengeneexpression AT zhengxinwang cgmpdependentproteinkinaseibinteractswithp44wdr77toregulateandrogenreceptordrivengeneexpression
_version_	1718423027205537792

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

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