Minh M Nguyen1, Robert M Harmon2, Zhou Wang1. 1. Department of Urology, School of Medicine Pittsburgh, University of Pittsburgh Cancer Institute PA 15232, USA. 2. Department of Pathology, Northwestern University Chicago, IL 60611, USA.
Abstract
BACKGROUND: Mechanisms regulating androgen receptor (AR) subcellular localization represent an essential component of AR signaling. Karyopherins are a family of nucleocytoplasmic trafficking factors. In this paper, we used the yeast model to study the effects of karyopherins on the subcellular localization of the AR. METHODS: Yeast mutants deficient in different nuclear transport factors were transformed with various AR based, GFP tagged constructs and their localization was monitored using microscopy. RESULTS: We showed that yeast can mediate androgen-induced AR nuclear localization and that in addition to the import factor, Importinα/β, this process required the import karyopherin Sxm1. We also showed that a previously identified nuclear export sequence (NES(AR)) in the ligand binding domain of AR does not appear to rely on karyopherins for cytoplasmic localization. CONCLUSIONS: These results suggest that while AR nuclear import relies on karyopherin activity, AR nuclear export and/or cytoplasmic localization may require other undefined mechanisms.
BACKGROUND: Mechanisms regulating androgen receptor (AR) subcellular localization represent an essential component of AR signaling. Karyopherins are a family of nucleocytoplasmic trafficking factors. In this paper, we used the yeast model to study the effects of karyopherins on the subcellular localization of the AR. METHODS:Yeast mutants deficient in different nuclear transport factors were transformed with various AR based, GFP tagged constructs and their localization was monitored using microscopy. RESULTS: We showed that yeast can mediate androgen-induced AR nuclear localization and that in addition to the import factor, Importinα/β, this process required the import karyopherin Sxm1. We also showed that a previously identified nuclear export sequence (NES(AR)) in the ligand binding domain of AR does not appear to rely on karyopherins for cytoplasmic localization. CONCLUSIONS: These results suggest that while AR nuclear import relies on karyopherin activity, AR nuclear export and/or cytoplasmic localization may require other undefined mechanisms.
Authors: Shidong Lv; Qiong Song; Guang Chen; Erdong Cheng; Wei Chen; Ryan Cole; Zeyu Wu; Laura E Pascal; Ke Wang; Peter Wipf; Joel B Nelson; Qiang Wei; Wenhua Huang; Zhou Wang Journal: J Clin Invest Date: 2021-02-15 Impact factor: 14.808
Authors: Y Jing; M M Nguyen; D Wang; L E Pascal; W Guo; Y Xu; J Ai; F-M Deng; K Z Masoodi; X Yu; J Zhang; J B Nelson; S Xia; Z Wang Journal: Oncogene Date: 2017-10-09 Impact factor: 9.867