The ubiquitin-specific protease USP10 modulates androgen receptor function.

The role of the ubiquitin/proteasome system in degrading nuclear hormone receptors and regulating their transcriptional function has emerged in the last few years. We identified the ubiquitin-specific protease USP10 as part of DNA-bound androgen receptor (AR) complexes purified from nuclear extracts of PC-3 cells stably expressing the AR. The interaction ...
between USP10 and the AR was confirmed by GST pull-down assays. Fluorescence microscopy documented that USP10 was localised in the nucleus and the cytoplasm. Cell-based transactivation assays in PC-3/AR cells revealed that overexpression of wild-type USP10, but not of an enzymatically inactive form, stimulated AR activity mediated by reporter constructs harbouring selective androgen response elements (AREs), non-selective steroid response elements (SREs) or the mouse mammary tumour virus (MMTV) promoter. Conversely, USP10 expression knock-down by siRNAs impaired the MMTV response to androgen. In summary, the data indicate that USP10 is a new cofactor that binds to the AR and stimulates the androgen response of target promoters. This finding underlines the role of the ubiquitin/proteasome system in modulating the AR function.
Mesh Terms:
Androgens, Animals, Cell Line, Tumor, Cell Nucleus, Cytoplasm, DNA, Neoplasm, Endopeptidases, Gene Expression Regulation, Neoplastic, Humans, Mice, Microscopy, Fluorescence, Promoter Regions, Genetic, Protein Binding, RNA, Small Interfering, Receptors, Androgen, Response Elements, Transcriptional Activation, Transfection, Ubiquitin Thiolesterase
Mol. Cell. Endocrinol.
Date: Dec. 21, 2005
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