The corepressors silencing mediator of retinoid and thyroid hormone receptor and nuclear receptor corepressor are involved in agonist- and antagonist-regulated transcription by androgen receptor.
Open accessAbstract
We have investigated the role of corepressors SMRT (silencing mediator of retinoid and thyroid hormone receptor) and N-CoR (nuclear receptor corepressor) in transcriptional regulation by androgen receptor (AR) in the LNCaP prostate cancer cell line. Using specific small interference RNAs to knock down SMRT and/or N-CoR in LNCaP cells, we found that SMRT and N-CoR not only mediate antagonist-dependent inhibition of AR activation but also have a widespread role in suppressing agonist-dependent activation of several AR target genes we have tested, including PSA (prostate-specific antigen), TSC22 (TSC22 domain family member 1), NKX3-1 (NK3 transcription factor locus 1), and B2M(beta-2-microglobulin). By sequencing analysis followed by analysis of physical association by chromatin immunoprecipitation assay, we mapped the putative androgen response elements in the NKX3-1 and B2M. Consistent with a role in both antagonist- and agonist-regulated transcription by AR, chromatin immunoprecipitation analysis revealed that both SMRT and N-CoR were recruited by AR to these genes in the presence of either flutamide or R1881. Knocking down SMRT and N-CoR enhanced the recruitment of the coactivators steroid receptor coactivator 1 and p300 by agonist-bound AR and led to increased hyperacetylation of histone H3 and H4, suggesting that the corepressors actively compete with coactivators for binding to agonist-bound AR. Taken together, our data indicate that SMRT and N-CoR corepressors are involved in transcriptional regulation by both agonist- and antagonist-bound AR and regulate the magnitude of hormone response, at least in part, by competing with coactivators.
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NCoR is a corepressor for androgen and estrogen receptors.
“Since then, it has been shown to be a corepressor molecule for androgen and estrogen receptors (19 -21).”
From The Nuclear Receptor Corepressor Has Organizational Effects within the Developing Amygdala on Juvenile Social Play and Anxiety-Like Behavior (2010) · cites this paper as [20]
NCoR appears to interact with both androgen and estrogen receptors.
“Because NCoR appears to interact with both androgen (19,20) and estrogen receptors (21), it is possible that reducing NCoR expression enhances the function of both nuclear receptors to further masculinize juvenile social play.”
From The Nuclear Receptor Corepressor Has Organizational Effects within the Developing Amygdala on Juvenile Social Play and Anxiety-Like Behavior (2010) · cites this paper as [20]
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References 56 · Cited by 120
Research works printed but not linked: 1
- Bohl CE, Miller DD, Chen J, Bell CE, Dalton JT 2005 Structural basis for accommodation of nonsteroidal li- gands in the androgen receptor. J Biol Chem 280: 37747-37754 Molecular Endocrinology is published monthly by The Endocrine Society (http://www.endo-society.org), the foremost professional society serving the endocrine community. 1060 Mol Endocrinol, May 2006, 20(5):1048-1060
- Authors
- Yoon, H.-G., & Wong, J.
- Affiliations
- Yonsei University (KR)
- Baylor College of Medicine (US)
- Corresponding author
- Wong, Jiemin
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2006-05
- Volume
- 20
- Issue
- 5
- Pages
- 1048-1060
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- OpenAlex
- W1971509596
- Cited by
- 120
- References
- 56
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 3 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 5 · 2015: 4 · 2014: 3 · 2013: 9 · 2012: 11
- FWCI
- 8.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK065264, DK065264)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- androgen receptor, SMRT, nuclear receptor corepressor, corepressors, transcriptional regulation, SRC-1, P300, histone acetylation, androgen response element, prostate cancer, LNCaP cells, NKX3.1, beta2-microglobulin, prostate-specific antigen
- MeSH terms
- Acetylation, Androgens, beta 2-Microglobulin, DNA-Binding Proteins, Enhancer Elements, Genetic, Gene Expression Regulation, Histones, Humans, Male, Nuclear Proteins, Prostatic Neoplasms, Receptors, Androgen, Repressor Proteins, Transcription Factors, Transcription, Genetic, Prostate-Specific Antigen, Homeodomain Proteins, RNA Interference, RNA, Small Interfering, Cell Line, Tumor, Nuclear Receptor Co-Repressor 1, Nuclear Receptor Co-Repressor 2, Androgen Receptor Antagonists
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