Androgen Receptor (AR) Coregulators: An Overview

Heinlein, Cynthia A.; Chang, Chawnshang

doi:10.1210/edrv.23.2.0460

Cited by 943Prostate Cancer Treatment and ResearchEstrogen and related hormone effectsSperm and Testicular Function

Androgen Receptor (AR) Coregulators: An Overview

Heinlein, Cynthia A., Chang, Chawnshang·2002·Endocrine Reviews

DOI 10.1210/edrv.23.2.0460

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Abstract

The biological action of androgens is mediated through the androgen receptor (AR). Androgen-bound AR functions as a transcription factor to regulate genes involved in an array of physiological processes, most notably male sexual differentiation and maturation, and the maintenance of spermatogenesis. The transcriptional activity of AR is affected by coregulators that influence a number of functional properties of AR, including ligand selectivity and DNA binding capacity. As the promoter of target genes, coregulators participate in DNA modification, either directly through modification of histones or indirectly by the recruitment of chromatin-modifying complexes, as well as functioning in the recruitment of the basal transcriptional machinery. Aberrant coregulator activity due to mutation or altered expression levels may be a contributing factor in the progression of diseases related to AR activity, such as prostate cancer. AR demonstrates distinct differences in its interaction with coregulators from other steroid receptors due to differences in the functional interaction between AR domains, possibly resulting in alterations in the dynamic interactions between coregulator complexes.

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Androgen receptors can be modulated by specific proteins called coregulators or mediated via activation of membrane-bound protein receptors to initiate intracellular signalling pathways, which can occur even in the presence of low levels of androgens.
“Androgen receptors can be modulated by specific proteins called coregulators [70–72] or mediated via the activation of membrane-bound protein receptors to initiate intracellular signalling pathways [73], which can occur even in the presence of low levels of androgens [74].”
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Phosphorylation of Steroid Receptor Coactivator-1
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Two distinct nuclear receptor interaction domains in NSD1, a novel SET protein that exhibits characteristics of both corepressors and coactivators
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Mice deficient in the steroid receptor co‐activator 1 (SRC‐1) are resistant to thyroid hormone
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The Nuclear Corepressors NCoR and SMRT Are Key Regulators of Both Ligand- and 8-Bromo-Cyclic AMP-Dependent Transcriptional Activity of the Human Progesterone Receptor
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Tip60 Is a Nuclear Hormone Receptor Coactivator
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Androgen Receptor Expression in Developing Male Reproductive Organs*
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Caveolin-1 Interacts with Androgen Receptor
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The C-terminal SET domains of ALL-1 and TRITHORAX interact with the INI1 and SNR1 proteins, components of the SWI/SNF complex
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Cloning and Characterization of Human Prostate Coactivator ARA54, a Novel Protein That Associates with the Androgen Receptor
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A Regulatory Role for RIP140 in Nuclear Receptor Activation
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Hsp90 Regulates Androgen Receptor Hormone Binding Affinity in Vivo
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CREB Binding Protein Is a Coactivator for the Androgen Receptor and Mediates Cross-talk with AP-1
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Proteasomal regulation of nuclear receptor corepressor-mediated repressionPreprint
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Growth factor involvement in progression of prostate cancer
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Discrimination between NL1- and NL2-Mediated Nuclear Localization of the Glucocorticoid Receptor
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The Linkage of Kennedy's Neuron Disease to ARA24, the First Identified Androgen Receptor Polyglutamine Region-associated Coactivator
Hsiao, P., Lin, D., Nakao, R., & Chang, C. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.29.20229 · Cited by 221 · see citing works
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Androgen Receptor in Prostate Cancer
Heinlein, C. A., & Chang, C. (2004) · Endocrine Reviews · doi:10.1210/er.2002-0032 · Cited by 1,780 · see citing works
Self-citation
Androgen Receptor (AR) Coregulators: A Diversity of Functions Converging on and Regulating the AR Transcriptional Complex
Heemers, H. V., & Tindall, D. J. (2007) · Endocrine Reviews · doi:10.1210/er.2007-0019 · Cited by 753 · see citing works
Androgens and Bone
Vanderschueren, D., Vandenput, L., Boonen, S., Lindberg, M. K., Bouillon, R., & Ohlsson, C. (2004) · Endocrine Reviews · doi:10.1210/er.2003-0003 · Cited by 717 · see citing works
Androgens and Cardiovascular Disease
Liu, P. Y., Death, A. K., & Handelsman, D. J. (2003) · Endocrine Reviews · doi:10.1210/er.2003-0005 · Cited by 690 · see citing works
Generation and characterization of androgen receptor knockout (ARKO) mice: An in vivo model for the study of androgen functions in selective tissues
Yeh, S., Tsai, M.-Y., Xu, Q., Mu, X., Lardy, H. A., Huang, K., Lin, H., Yeh, S.-D., Altuwaijri, S., Zhou, X., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.212474399 · Cited by 668 · see citing works
Self-citation
Androgen Receptor Structure, Function and Biology: From Bench to Bedside.
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Pharmacology of anabolic steroids
Kicman, A. T. (2008) · British Journal of Pharmacology · doi:10.1038/bjp.2008.165 · Cited by 578 · see citing works
The Roles of Androgen Receptors and Androgen-Binding Proteins in Nongenomic Androgen Actions
Heinlein, C. A., & Chang, C. (2002) · Molecular Endocrinology · doi:10.1210/me.2002-0070 · Cited by 568 · see citing works
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Chemistry and Structural Biology of Androgen Receptor
Gao, W., Bohl, C. E., & Dalton, J. T. (2005) · Chemical Reviews · doi:10.1021/cr020456u · Cited by 527 · see citing works
Sex differences in lipid and lipoprotein metabolism
Palmisano, B. T., Zhu, L., Eckel, R. H., & Stafford, J. M. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.05.008 · Cited by 535 · see citing works
Direct effects of sex steroid hormones on adipose tissues and obesity
Mayes, J., & Watson, G. (2004) · Obesity Reviews · doi:10.1111/j.1467-789x.2004.00152.x · Cited by 502 · see citing works
Non-genomic actions of androgens
Foradori, C. D., Weiser, M. J., & Handa, R. J. (2008) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2007.10.005 · Cited by 493 · see citing works
Nuclear Receptor Coregulators: Judges, Juries, and Executioners of Cellular Regulation
Lonard, D. M., & O’Malley, B. W. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.08.012 · Cited by 489 · see citing works
SUMOylation and De-SUMOylation: Wrestling with Life's Processes
Yeh, E. T. H. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.r800050200 · Cited by 469 · see citing works
Infertility with defective spermatogenesis and hypotestosteronemia in male mice lacking the androgen receptor in Sertoli cells
Chang, C., Chen, Y.-T., Yeh, S., Xu, Q., Wang, R.-S., Guillou, F., Lardy, H. A., & Yeh, S. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307306101 · Cited by 468 · see citing works
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Androgen Receptor Roles in Spermatogenesis and Fertility: Lessons from Testicular Cell-Specific Androgen Receptor Knockout Mice
Wang, R.-S., Yeh, S., Tzeng, C., & Chang, C. (2009) · Endocrine Reviews · doi:10.1210/er.2008-0025 · Cited by 470 · see citing works
Self-citation
Phosphorylation‐dependent ubiquitylation and degradation of androgen receptor by Akt require Mdm2 E3 ligase
Lin, H.-K., Wang, L., Hu, Y., Altuwaijri, S., & Chang, C. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf406 · Cited by 450 · see citing works
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Spatial and Temporal Recruitment of Androgen Receptor and Its Coactivators Involves Chromosomal Looping and Polymerase Tracking
Wang, Q., Carroll, J. S., & Brown, M. A. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.07.018 · Cited by 450 · see citing works
Progestogens Used in Postmenopausal Hormone Therapy: Differences in Their Pharmacological Properties, Intracellular Actions, and Clinical Effects
Stanczyk, F. Z., Hapgood, J. P., Winer, S., & Mishell, D. R. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1008 · Cited by 429 · see citing works
Androgen receptors in hormone-dependent and castration-resistant prostate cancer
Shafi, A. A., Yen, A. E., & Weigel, N. L. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.07.003 · Cited by 422 · see citing works
Sex differences and sex steroids in lung health and disease
Townsend, E. A., Miller, V. M., & Prakash, Y. S. (2012) · Endocrine Reviews · doi:10.1210/er.2010-0031 · Cited by 395 · see citing works
Androgen receptor: A key molecule in the progression of prostate cancer to hormone independence
Taplin, M., & Balk, S. P. (2003) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10653 · Cited by 392 · see citing works
Dual role of FoxA1 in androgen receptor binding to chromatin, androgen signalling and prostate cancer
Sahu, B., Laakso, M., Ovaska, K., Mirtti, T. K., Lundin, J. E., Rannikko, A. S., Sankila, A., Turunen, J.-P., Lundin, M., Konsti, J., et al. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.328 · Cited by 386 · see citing works
The functional role of long non-coding RNAs and epigenetics
Cao, J. (2014) · Biological Procedures Online · doi:10.1186/1480-9222-16-11 · Cited by 359 · see citing works
Use of doping agents, particularly anabolic steroids, in sports and society
Sjöqvist, F., Garle, M., & Rane, A. (2008) · The Lancet · doi:10.1016/s0140-6736(08)60801-6 · Cited by 349 · see citing works
AR, the cell cycle, and prostate cancer
Balk, S. P., & Knudsen, K. E. (2008) · Nuclear Receptor Signaling · doi:10.1621/nrs.06001 · Cited by 338 · see citing works
Androgen deprivation therapy for prostate cancer: Current status and future prospects
Miyamoto, H., Messing, E. M., & Chang, C. (2004) · The Prostate · doi:10.1002/pros.20115 · Cited by 318 · see citing works
Self-citation
Subfertility and defective folliculogenesis in female mice lacking androgen receptor
Hu, Y., Wang, P., Yeh, S., Wang, R.-S., Xie, C. L., Xu, Q., Zhou, X., Chao, H., Tsai, M., & Chang, C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404372101 · Cited by 316 · see citing works
Self-citation
Drug Insight: testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging
Bhasin, S., Calof, O. M., Storer, T. W., Lee, M. L., Mazer, N. A., Jasuja, R., Montori, V. M., Gao, W., & Dalton, J. T. (2006) · Nature Clinical Practice Endocrinology &#38 Metabolism · doi:10.1038/ncpendmet0120 · Cited by 300 · see citing works
Androgen receptor driven transcription in molecular apocrine breast cancer is mediated by FoxA1
Robinson, J. L. L., MacArthur, S., Ross-Innes, C. S., Tilley, W. D., Neal, D. E., Mills, I. G., & Carroll, J. S. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.216 · Cited by 300 · see citing works
Molecular cell biology of androgen receptor signalling
Bennett, N. C., Gardiner, R. A., Hooper, J. D., Johnson, D. W., & Gobe, G. C. (2010) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2009.11.013 · Cited by 292 · see citing works
The Role of Hepatocyte Nuclear Factor-3α (Forkhead Box A1) and Androgen Receptor in Transcriptional Regulation of Prostatic Genes
Gao, N., Zhang, J., Rao, M. A., Case, T. C., Mirosevich, J., Wang, Y., Jin, R., Gupta, A., Rennie, P. S., & Matusik, R. J. (2003) · Molecular Endocrinology · doi:10.1210/me.2003-0020 · Cited by 279 · see citing works
Molecular Mechanisms in Spermatogenesis
Cheng, C.-Y. (2008) · Advances in experimental medicine and biology · doi:10.1007/978-0-387-09597-4 · Cited by 278 · see citing works
DU‐145 and PC‐3 human prostate cancer cell lines express androgen receptor: Implications for the androgen receptor functions and regulation
Alimirah, F., Chen, J., Basrawala, Z. K., Xin, H., & Choubey, D. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.03.041 · Cited by 264 · see citing works
Androgen Receptor Is a New Potential Therapeutic Target for the Treatment of Hepatocellular Carcinoma
Ma, W., Hsu, C., Wu, M., Wu, C., Wu, C., Lai, J., Jou, Y., Chen, C.-W. D., Yeh, S., & Chang, C. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.05.046 · Cited by 253 · see citing works
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Targeting cytochrome P450 enzymes: A new approach in anti-cancer drug development
Bruno, R. D., & Njar, V. C. O. (2007) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2007.05.046 · Cited by 253 · see citing works
Development of selective androgen receptor modulators (SARMs)
Narayanan, R., Coss, C. C., & Dalton, J. T. (2018) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.06.013 · Cited by 251 · see citing works
Sex differences in vascular physiology and pathophysiology: estrogen and androgen signaling in health and disease
Boese, A. C., Kim, S. C., Yin, K., Lee, J., & Hamblin, M. H. (2017) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00217.2016 · Cited by 241 · see citing works
Androgen receptor and androgen-dependent gene expression in lung
Mikkonen, L., Pihlajamaa, P., Sahu, B., Zhang, F., & Jänne, O. A. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.12.022 · Cited by 243 · see citing works
Androgen Receptor Variants Occur Frequently in Castration Resistant Prostate Cancer Metastases
Zhang, X., Morrissey, C. M., Sun, S., Ketchandji, M., Nelson, P. S., True, L. D., Vakar‐Lopez, F., Vessella, R. L., & Plymate, S. R. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027970 · Cited by 240 · see citing works
Molecular mechanisms of steroid receptor-mediated actions by synthetic progestins used in HRT and contraception
Africander, D., Verhoog, N. J. D., & Hapgood, J. P. (2011) · Steroids · doi:10.1016/j.steroids.2011.03.001 · Cited by 244 · see citing works
Androgen‐inducible TGF‐β1 from balding dermal papilla cells inhibits epithelial cell growth: a clue to understanding paradoxical effects of androgen on human hair growth
Inui, S., Fukuzato, Y., Nakajima, T., Yoshikawa, K., & Itami, S. (2002) · The FASEB Journal · doi:10.1096/fj.02-0043fje · Cited by 239 · see citing works
Diverse roles of androgen receptor (AR) domains in AR-mediated signaling
Claessens, F., Denayer, S., Tilborgh, N. V., Kerkhofs, S., Helsen, C., & Haelens, A. (2008) · Nuclear Receptor Signaling · doi:10.1621/nrs.06008 · Cited by 232 · see citing works
Increased Expression of Androgen Receptor Sensitizes Prostate Cancer Cells to Low Levels of Androgens
Waltering, K. K., Helenius, M. A., Sahu, B., Manni, V., Linja, M. J., Jänne, O. A., & Visakorpi, T. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-0919 · Cited by 228 · see citing works
Selective androgen receptor modulators as function promoting therapies
Bhasin, S., & Jasuja, R. (2009) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e32832a3d79 · Cited by 223 · see citing works
Molecular basis of androgenetic alopecia: from androgen to paracrine mediators through dermal papilla
Inui, S., & Itami, S. (2011) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2010.10.015 · Cited by 221 · see citing works
Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs)
Gao, W., & Dalton, J. T. (2007) · Drug Discovery Today · doi:10.1016/j.drudis.2007.01.003 · Cited by 216 · see citing works
Triclocarban Enhances Testosterone Action: A New Type of Endocrine Disruptor?
Chen, J., Ahn, K. C., Gee, N. A., Ahmed, M. I., Dulęba, A. J., Zhao, L., Gee, S. J., Hammock, B. D., & Lasley, B. L. (2007) · Endocrinology · doi:10.1210/en.2007-1057 · Cited by 214 · see citing works
Androgen receptor (AR) differential roles in hormone-related tumors including prostate, bladder, kidney, lung, breast and liver
Chang, C., Lee, S. O., Yeh, S., & Chang, T. M. (2013) · Oncogene · doi:10.1038/onc.2013.274 · Cited by 214 · see citing works
Self-citation
Increased hepatic steatosis and insulin resistance in mice lacking hepatic androgen receptor
Lin, H., Yu, I.-C. I., Wang, R.-S., Chen, Y., Liu, N.-C., Altuwaijri, S., Hsu, C., Ma, W., Jokinen, J. D., Sparks, J. D., et al. (2008) · Hepatology · doi:10.1002/hep.22252 · Cited by 210 · see citing works
Self-citation
Androgens and androgen receptor action in skin and hair follicles
Ceruti, J. M., Leirós, G. J., & Balañá, M. E. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.09.009 · Cited by 212 · see citing works
Epidermal Growth Factor Increases Coactivation of the Androgen Receptor in Recurrent Prostate Cancer
Gregory, C. W., Fei, X., Ponguta, L. A., He, B., Bill, H. M., French, F. S., & Wilson, E. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m307649200 · Cited by 201 · see citing works
Filamin-A fragment localizes to the nucleus to regulate androgen receptor and coactivator functions
Loy, C. J., Sim, K. S., & Yong, E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0736237100 · Cited by 202 · see citing works
Involvement of Proteasome in the Dynamic Assembly of the Androgen Receptor Transcription Complex*
Kang, Z., Pirskanen, A., Jänne, O., & Palvimo, J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m209074200 · Cited by 204 · see citing works
Circular RNA expression is suppressed by androgen receptor (AR)-regulated adenosine deaminase that acts on RNA (ADAR1) in human hepatocellular carcinoma
Shi, L., Yan, P., Liang, Y., Sun, Y., Shen, J., Zhou, S., Lin, H. M., Liang, X. H., & Cai, X. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.556 · Cited by 196 · see citing works
Androgen Receptor Signaling in the Development of Castration-Resistant Prostate Cancer
Feng, Q. F., & He, B. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00858 · Cited by 197 · see citing works
Targeting the androgen receptor pathway in castration-resistant prostate cancer: progresses and prospects
Ferraldeschi, R., Welti, J. C., Luo, J., Attard, G., & Bono, J. S. D. (2014) · Oncogene · doi:10.1038/onc.2014.115 · Cited by 194 · see citing works
Androgen Receptor in Sertoli Cell Is Essential for Germ Cell Nursery and Junctional Complex Formation in Mouse Testes
Wang, R.-S., Yeh, S., Chen, L.-M., Lin, H., Zhang, C., Ni, J., Wu, C., di Sant'Agnese, P. A., Bentley, K. L. D. M., Tzeng, C., et al. (2006) · Endocrinology · doi:10.1210/en.2006-0138 · Cited by 191 · see citing works
Self-citation
Suppression Versus Induction of Androgen Receptor Functions by the Phosphatidylinositol 3-Kinase/Akt Pathway in Prostate Cancer LNCaP Cells with Different Passage Numbers
Lin, H., Hu, Y., Yang, L., Altuwaijri, S., Chen, Y.-T., Kang, H., & Chang, C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300676200 · Cited by 187 · see citing works
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Regulation of Androgen Receptor Activity by the Nuclear Receptor Corepressor SMRT*
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Authors: Heinlein, C. A., & Chang, C.
Affiliations: University of Rochester Medicine (US)
Corresponding author: Chang, Chawnshang
ORCID: Chang, Chawnshang
Venue: Endocrine Reviews
Publisher: The Endocrine Society
Published: 2002-04-01
Volume: 23
Issue: 2
Pages: 175-200
ISSN: 0163-769X (ISSN-L)
1945-7189
DOI: 10.1210/edrv.23.2.0460
OpenAlex: W2161123101
Cited by: 943
References: 357
Citations by year: 2026: 13 · 2025: 18 · 2024: 28 · 2023: 22 · 2022: 30 · 2021: 19 · 2020: 26 · 2019: 25 · 2018: 23 · 2017: 30 · 2016: 32 · 2015: 48 · 2014: 34 · 2013: 48 · 2012: 44
FWCI: 12.87
Type: journal article
Language: en
Open access: closed
Locations: Endocrine Reviews (publishedVersion)
PubMed (publishedVersion)
Funders: University of Rochester
National Institutes of Health (14642)
Medical Center, University of Rochester
National Cancer Institute (CA55639, CA-715670)
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
Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
Keywords: androgen receptor, coregulators, transcriptional regulation, androgen signaling, histone modifications, chromatin remodeling, basal transcription machinery, ligand selectivity, DNA binding, prostate cancer, steroid hormone receptors, male sexual differentiation, spermatogenesis
MeSH terms: Animals, Gene Expression Regulation, Humans, Male, Mutation, Prostatic Neoplasms, Receptors, Androgen, Transcription Factors, Transcription, Genetic, Signal Transduction

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Androgen Receptor (AR) Coregulators: An Overview

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