Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/79578
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Type: Journal article
Title: Ski-interacting protein (SKIP) interacts with androgen receptor in the nucleus and modulates androgen-dependent transcription
Author: Abankwa, D.
Millard, S.
Martel, N.
Choong, C.
Yang, M.
Butler, L.
Buchanan, G.
Tilley, W.
Ueki, N.
Hayman, M.
Leong, G.
Citation: BMC Biochemistry, 2013; 14(10):1-9
Publisher: BioMed Central Ltd
Issue Date: 2013
ISSN: 1471-2091
1471-2091
Statement of
Responsibility: 
Daniel Abankwa, Susan M. Millard, Nick Martel, Catherine S. Choong, Miao Yang, Lisa M. Butler, Grant Buchanan, Wayne D Tilley, Nobuhide Ueki, Michael J Hayman and Gary M Leong
Abstract: BACKGROUND: The androgen receptor (AR) is a member of the nuclear receptor (NR) superfamily of ligand-inducible DNA transcription factors, and is the major mediator of male sexual development, prostate growth and the pathogenesis of prostate cancer. Cell and gene specific regulation by the AR is determined by availability of and interaction with sets of key accessory cofactors. Ski-interacting protein (SKIP; SNW1, NCOA62) is a cofactor shown to interact with several NRs and a diverse range of other transcription factors. Interestingly, SKIP as part of the spliceosome is thought to link mRNA splicing with transcription. SKIP has not been previously shown to interact with the AR. RESULTS: The aim of this study was to investigate whether SKIP interacts with the AR and modulates AR-dependent transcription. Here, we show by co-immunoprecipitation experiments that SKIP is in a complex with the AR. Moreover, SKIP increased 5α-dihydrotestosterone (DHT) induced N-terminal/C-terminal AR interaction from 12-fold to almost 300-fold in a two-hybrid assay, and enhanced AR ligand-independent AF-1 transactivation. SKIP augmented ligand- and AR-dependent transactivation in PC3 prostate cancer cells. Live-cell imaging revealed a fast (half-time=129 s) translocation of AR from the cytoplasm to the nucleus upon DHT-stimulation. Förster resonance energy transfer (FRET) experiments suggest a direct AR-SKIP interaction in the nucleus upon translocation. CONCLUSIONS: Our results suggest that SKIP interacts with AR in the nucleus and enhances AR-dependent transactivation and N/C-interaction supporting a role for SKIP as an AR co-factor.
Keywords: COS Cells; Cell Line, Tumor; Cell Nucleus; Animals; Cercopithecus aethiops; Humans; Dihydrotestosterone; Receptors, Androgen; Fluorescence Resonance Energy Transfer; Immunoprecipitation; Protein Structure, Tertiary; Protein Binding; Genes, Reporter; Male; Transcriptional Activation; Nuclear Receptor Coactivators; HEK293 Cells
Description: Extent: 9 p.
Rights: © 2013 Abankwa et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
RMID: 0020130284
DOI: 10.1186/1471-2091-14-10
Appears in Collections:Medicine publications

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