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Lookup NU author(s): Dr Luke GaughanORCiD, Dr Ian Logan, Susan Cook, Professor David Neal, Professor Craig Robson
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The androgen receptor (AR), a member of the nuclear hormone receptor superfamily, is thought to play an important role in the development of prostate cancer. The AR is a hormone-dependent transcription factor that activates expression of numerous androgen-responsive genes. Histone acetyltransferase-containing proteins have been shown to increase activity of several transcription factors, including nuclear hormone receptors, by eliciting histone acetylation, which facilitates promoter access to the transcriptional machinery. Conversely, histone deacetylases (HDACs) have been identified which reduce levels of histone acetylation and are associated with transcriptional repression by various transcription factors. We have previously shown that Tip60 (Tat-interactive protein, 60 kDa) is a bona fide co-activator protein for the AR. Here we show that Tip60 directly acetylates the AR, which we demonstrate is a requisite for Tip60-mediated transcription. To define a mechanism for repression of AR function, we demonstrate that AR activity is specifically down-regulated by the histone deacetylase activity of HDAC1. Furthermore, using both mammalian two-hybrid and immunoprecipitation experiments, we show that AR and HDAC1 interact, suggestive of a direct role for down-regulation of AR activity by HDAC1. In chromatin immunoprecipitation assays, we provide evidence that AR, Tip60, and HDAC1 form a trimeric complex upon the endogenous AR-responsive PSA promoter, suggesting that acetylation and deacetylation of the AR is an important mechanism for regulating transcriptional activity.
Author(s): Gaughan, L., Logan, I. R., Cook, S., Neal, D. E., Robson, C. N.
Publication type: Article
Publication status: Published
Journal: Journal of Biological Chemistry
Year: 2002
Volume: 277
Issue: 29
Pages: 25904-25913
Print publication date: 19/07/2002
ISSN (print): 0021-9258
ISSN (electronic): 1083-351X
URL: http://dx.doi.org/10.1074/jbc.M203423200
DOI: 10.1074/jbc.M203423200
PubMed id: 11994312
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