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Regulation of the androgen receptor by SET9-mediated methylation

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.

Publication metadata

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


DOI: 10.1093/nar/gkq861


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