Document Type
Article
Publication Date
3-1-2011
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.
Recommended Citation
Gaughan, Luke; Stockley, Jacqueline; Wang, Nan; McCracken, Stuart R C; Treumann, Achim; Armstrong, Kelly; Shaheen, Fadhel; Watt, Kate; McEwan, Iain J; Wang, Chenguang; Pestell, Richard; and Robson, Craig N, "Regulation of the androgen receptor by SET9-mediated methylation." (2011). Kimmel Cancer Center Faculty Papers. Paper 31.
https://jdc.jefferson.edu/kimmelccfp/31
PubMed ID
20959290
Comments
This article has been peer reviewed. It is the authors' final version prior to publication in Nucleic acids research.
Volume 39, Issue 4, March 2011, Pages 1266-79.
The published version is available at DOI: 10.1093/nar/gkq861. Copyright © Oxford Journals.