The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Tip60 and Histone Deacetylase 1 Regulate Androgen Receptor Activity through Changes to the Acetylation Status of the Receptor
Open accessAbstract
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.
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Cites
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Steroid receptor coactivator-1 is a histone acetyltransferase
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Cited by
Acetylation and deacetylation of non-histone proteins
Glozak, M. A., Sengupta, N., Zhang, X., & Seto, E. (2005) · Gene · doi:10.1016/j.gene.2005.09.010 · Cited by 1,584
Histone Deacetylase Inhibitors in Cancer Therapy
Lane, A. A., & Chabner, B. A. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.22.1291 · Cited by 874
Heemers, H. V., & Tindall, D. J. (2007) · Endocrine Reviews · doi:10.1210/er.2007-0019 · Cited by 753
(2011) · PubMed Central · Cited by 560
Combining epigenetic drugs with other therapies for solid tumours — past lessons and future promise
Morel, D., Jeffery, D., Aspeslagh, S., Almouzni, G., & Postel-Vinay, S. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0267-4 · Cited by 445
Metadata
- Authors
- Gaughan, L., Logan, I. R., Cook, S., Neal, D. E., & Robson, C. N.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-07
- Volume
- 277
- Issue
- 29
- Pages
- 25904-25913
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1991995900
- Cited by
- 310
- References
- 40
- FWCI
- 4.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Gaughan, L., Logan, I. R., Cook, S., Neal, D. E., & Robson, C. N. (2002). Tip60 and Histone Deacetylase 1 Regulate Androgen Receptor Activity through Changes to the Acetylation Status of the Receptor. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m203423200
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