Nuclear transport signals control cellular localization and function of androgen receptor cofactor p44/WDR77.

The androgen receptor (AR) cofactor p44/WDR77, which regulates expression of a set of androgen target genes, is required for differentiation of prostate epithelium. Aberrant localization of p44/WDR77 in the cytoplasm is associated with prostate tumorigenesis. Here, we describe studies that used the...

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Autores principales:	Zhongping Gu, Liran Zhou, Shen Gao, Zhengxin Wang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5c9e2c3729f44c5ba9c0a3e60d18bc51
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spelling	oai:doaj.org-article:5c9e2c3729f44c5ba9c0a3e60d18bc512021-11-18T06:50:09ZNuclear transport signals control cellular localization and function of androgen receptor cofactor p44/WDR77.1932-620310.1371/journal.pone.0022395https://doaj.org/article/5c9e2c3729f44c5ba9c0a3e60d18bc512011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21789256/?tool=EBIhttps://doaj.org/toc/1932-6203The androgen receptor (AR) cofactor p44/WDR77, which regulates expression of a set of androgen target genes, is required for differentiation of prostate epithelium. Aberrant localization of p44/WDR77 in the cytoplasm is associated with prostate tumorigenesis. Here, we describe studies that used the mouse prostate and human prostate cancer cells as model systems to investigate signals that control subcellular localization of p44/WDR77. We observed distinct subcellular location of p44/WDR77 during prostate development. p44/WDR77 localizes in the cytoplasm at the early stage of prostate development, when prostate epithelial cells are rapidly proliferating, and in the nucleus in adult prostate, when epithelial cells are fully differentiated. Subcellular localization assays designed to span the entire open-reading frame of p44/WDR77 protein revealed the presence of two nuclear exclusion signal (NES) and three nuclear localization signal (NLS) sequences in the p44/WDR77 protein. Site-directed mutagenesis of critical residues within an NLS led to loss of nuclear localization and transcriptional activity of p44/WDR77, suggesting that nuclear localization of p44/WDR77 is essential for its function as a transcriptional cofactor for AR. Three identified NLS were not functional in AR-positive prostate cancer (LNCaP and 22RV1) cells, which led to localization of p44/WDR77 in cytoplasm. The function of NLS in LNCaP cells could be restored by factor(s) from Cos 7 or PC3 cells. Mass spectrometric (MALDI-TOF/TOF) analysis identified proteins associated with an NLS and an NES in prostate cancer cells. These results provide a basis for understanding subcellular transport of p44/WDR77 during prostate development and tumorigenesis.Zhongping GuLiran ZhouShen GaoZhengxin WangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 7, p e22395 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zhongping Gu Liran Zhou Shen Gao Zhengxin Wang Nuclear transport signals control cellular localization and function of androgen receptor cofactor p44/WDR77.
description	The androgen receptor (AR) cofactor p44/WDR77, which regulates expression of a set of androgen target genes, is required for differentiation of prostate epithelium. Aberrant localization of p44/WDR77 in the cytoplasm is associated with prostate tumorigenesis. Here, we describe studies that used the mouse prostate and human prostate cancer cells as model systems to investigate signals that control subcellular localization of p44/WDR77. We observed distinct subcellular location of p44/WDR77 during prostate development. p44/WDR77 localizes in the cytoplasm at the early stage of prostate development, when prostate epithelial cells are rapidly proliferating, and in the nucleus in adult prostate, when epithelial cells are fully differentiated. Subcellular localization assays designed to span the entire open-reading frame of p44/WDR77 protein revealed the presence of two nuclear exclusion signal (NES) and three nuclear localization signal (NLS) sequences in the p44/WDR77 protein. Site-directed mutagenesis of critical residues within an NLS led to loss of nuclear localization and transcriptional activity of p44/WDR77, suggesting that nuclear localization of p44/WDR77 is essential for its function as a transcriptional cofactor for AR. Three identified NLS were not functional in AR-positive prostate cancer (LNCaP and 22RV1) cells, which led to localization of p44/WDR77 in cytoplasm. The function of NLS in LNCaP cells could be restored by factor(s) from Cos 7 or PC3 cells. Mass spectrometric (MALDI-TOF/TOF) analysis identified proteins associated with an NLS and an NES in prostate cancer cells. These results provide a basis for understanding subcellular transport of p44/WDR77 during prostate development and tumorigenesis.
format	article
author	Zhongping Gu Liran Zhou Shen Gao Zhengxin Wang
author_facet	Zhongping Gu Liran Zhou Shen Gao Zhengxin Wang
author_sort	Zhongping Gu
title	Nuclear transport signals control cellular localization and function of androgen receptor cofactor p44/WDR77.
title_short	Nuclear transport signals control cellular localization and function of androgen receptor cofactor p44/WDR77.
title_full	Nuclear transport signals control cellular localization and function of androgen receptor cofactor p44/WDR77.
title_fullStr	Nuclear transport signals control cellular localization and function of androgen receptor cofactor p44/WDR77.
title_full_unstemmed	Nuclear transport signals control cellular localization and function of androgen receptor cofactor p44/WDR77.
title_sort	nuclear transport signals control cellular localization and function of androgen receptor cofactor p44/wdr77.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/5c9e2c3729f44c5ba9c0a3e60d18bc51
work_keys_str_mv	AT zhongpinggu nucleartransportsignalscontrolcellularlocalizationandfunctionofandrogenreceptorcofactorp44wdr77 AT liranzhou nucleartransportsignalscontrolcellularlocalizationandfunctionofandrogenreceptorcofactorp44wdr77 AT shengao nucleartransportsignalscontrolcellularlocalizationandfunctionofandrogenreceptorcofactorp44wdr77 AT zhengxinwang nucleartransportsignalscontrolcellularlocalizationandfunctionofandrogenreceptorcofactorp44wdr77
_version_	1718424294245007360

Nuclear transport signals control cellular localization and function of androgen receptor cofactor p44/WDR77.

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