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Lookup NU author(s): Dr Luke GaughanORCiD, Dr Jacqueline Stockley, Nan Wang, Dr Stuart McCracken, Dr Kelly Coffey, Dr Fadhel Shaheen, Professor Craig Robson
The androgen receptor (AR) is a member of the nuclear hormone receptor family of transcription factors that plays a critical role in regulating expression of genes involved in prostate development and transformation. Upon hormone binding, the AR associates with numerous co-regulator proteins that regulate the activation status of target genes via flux to the post-translational modification status of histones and the receptor. Here we show that the AR interacts with and is directly methylated by the histone methyltransferase enzyme SET9. Methylation of the AR on lysine 632 is necessary for enhancing transcriptional activity of the receptor by facilitating both inter-domain communication between the N- and C-termini and recruitment to androgen-target genes. We also show that SET9 is pro-proliferative and anti-apoptotic in prostate cancer cells and demonstrates up-regulated nuclear expression in prostate cancer tissue. In all, our date indicate a new mechanism of AR regulation that may be therapeutically exploitable for prostate cancer treatment.
Author(s): Gaughan L, Stockley J, Wang N, McCracken S, Truemann A, Armstrong K, Shaheen F, Watt K, McEwan I, Wang C, Pestell RG, Robson CN
Publication type: Article
Publication status: Published
Journal: Nucleic Acids Research
Year: 2011
Volume: 39
Issue: 4
Pages: 1266-1279
Print publication date: 01/03/2011
Date deposited: 07/02/2012
ISSN (print): 0305-1048
ISSN (electronic): 1362-4962
Publisher: Oxford University Press
URL: http://dx.doi.org/10.1093/nar/gkq861
DOI: 10.1093/nar/gkq861
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