Abstract:
: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.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Gaughan L,Stockley J,Wang N,McCracken SR,Treumann A,Armstrong K,Shaheen F,Watt K,McEwan IJ,Wang C,Pestell RG,Robson CNdoi
10.1093/nar/gkq861subject
Has Abstractpub_date
2011-03-01 00:00:00pages
1266-79issue
4eissn
0305-1048issn
1362-4962pii
gkq861journal_volume
39pub_type
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