N-terminal domain of the androgen receptor contains a region that can promote cytoplasmic localization

被引：10

作者：

Dar, Javid A. ^{[1
]}

Eisermann, Kurtis ^{[1
]}

Masoodi, Khalid Z. ^{[1
]}

Ai, Junkui ^{[1
]}

Wang, Dan ^{[1
]}

Severance, Tyler ^{[1
]}

Sampath-Kumar, Sharanya D. ^{[1
]}

Wang, Zhou ^{[1
,2
,3
]}

机构：

[1] Univ Pittsburgh, Dept Urol, Pittsburgh, PA USA

[2] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA

[3] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA

来源：

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY | 2014年 / 139卷

关键词：

Androgen receptor; NTD; Subcellular localization; AR(50-250); Leptomycin B; PROSTATE-CANCER; NUCLEAR IMPORT; COMPLEMENTARY-DNA; EXPORT; SIGNAL; IDENTIFICATION; TRAFFICKING; MODULATION; PROTEINS; BINDING;

D O I：

10.1016/j.jsbmb.2013.09.013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Nucleocytoplasmic trafficking of the androgen receptor (AR) represents an essential step in androgen action. To determine whether the amino-terminal domain (NTD) contains potential nuclear import and/or export signals, deletion mutants of the NTD tagged with green fluorescent protein (GFP) were generated and tested for their intracellular localization in both AR-negative and AR-positive cell lines. Subcellular localization analysis suggested a role of the NTD in regulating AR subcellular localization and revealed that the region of a.a. 50-250 of the NTD of AR (AR(50-250)) could promote cytoplasmic localization. Leptomycin B inhibited the activity of AR(50-250), suggesting that AR(50-250) export is mediated through exportin 1, either directly or indirectly. These observations argue for an important role of the NTD in regulating AR nucleocytoplasmic trafficking and will facilitate further investigation of interactions among different signals in regulating AR nucleocytoplasmic trafficking, which may lead to new approaches to inhibit AR nuclear localization. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：16 / 24

页数：9

共 32 条

[1] HDAC6 Regulates Androgen Receptor Hypersensitivity and Nuclear Localization via Modulating Hsp90 Acetylation in Castration-Resistant Prostate Cancer [J].