ArticleThe Journal of biological chemistry2012
The in vivo role of androgen receptor SUMOylation as revealed by androgen insensitivity syndrome and prostate cancer mutations targeting the proline/glycine residues of synergy control motifs.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- The impact of dysregulation SUMOylation on prostate cancer.Journal of translational medicine · 2025Review
- Review
- The Prognosis-Predictive and Immunoregulatory Role of SUMOylation Related Genes: Potential Novel Targets in Prostate Cancer Treatment.International journal of molecular sciences · 2023Article
- Post-Translational Modifications That Drive Prostate Cancer Progression.Biomolecules · 2021Review
- Steroidogenic Factor 1 (NR5A1) Activates ATF3 Transcriptional Activity.International journal of molecular sciences · 2020Article
- Lack of androgen receptor SUMOylation results in male infertility due to epididymal dysfunction.Nature communications · 2019Article
- SUMO2/3 modification of activating transcription factor 5 (ATF5) controls its dynamic translocation at the centrosome.The Journal of biological chemistry · 2018Article
- SUMO and the robustness of cancer.Nature reviews. Cancer · 2017Review
- Metabolomic profiling identifies potential pathways involved in the interaction of iron homeostasis with glucose metabolism.Molecular metabolism · 2017Article
- Regulation of germ cell function by SUMOylation.Cell and tissue research · 2016Review
- Identification and Characterization of the Androgen Receptor From the American Alligator, Alligator mississippiensis.Endocrinology · 2015Article
- Disrupting SUMOylation enhances transcriptional function and ameliorates polyglutamine androgen receptor-mediated disease.The Journal of clinical investigation · 2015Article
- Fighting polyglutamine disease by wrestling with SUMO.The Journal of clinical investigation · 2015Article
- Overview on the complexity of androgen receptor-targeted therapy for prostate cancer.Cancer cell international · 2015Article
- Nuclear mobility and activity of FOXA1 with androgen receptor are regulated by SUMOylation.Molecular endocrinology (Baltimore, Md.) · 2014Article
- Targeting nuclear receptors with marine natural products.Marine drugs · 2014Review
- 19q13.11 microdeletion concomitant with ins(2;19)(p25.3;q13.1q13.4)dn in a boy: potential role of UBA2 in the associated phenotype.Molecular cytogenetics · 2014Article
- Sarcosine as a potential prostate cancer biomarker--a review.International journal of molecular sciences · 2013Review
- Loss of SUMOylation on ATF3 inhibits proliferation of prostate cancer cells by modulating CCND1/2 activity.International journal of molecular sciences · 2013Article
- PIASγ enhanced SUMO-2 modification of Nurr1 activation-function-1 domain limits Nurr1 transcriptional synergy.PloS one · 2013Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The androgen receptor (AR) mediates the effects of male sexual hormones on development and physiology. Alterations in AR function are central to reproductive disorders, prostate cancer, and Kennedy disease. AR activity is influenced by post-translational modifications, but their role in AR-based diseases is poorly understood. Conjugation by small ubiquitin-like modifier (SUMO) proteins at two synergy control (SC) motifs in AR exerts a promoter context-dependent inhibitory role. SC motifs are composed of a four-amino acid core that is often preceded and/or followed by nearby proline or glycine residues. The function of these flanking residues, however, has not been examined directly. Remarkably, several AR mutations associated with oligospermia and androgen insensitivity syndrome map to Pro-390, the conserved proline downstream of the first SC motif in AR. Similarly, mutations at Gly-524, downstream of the second SC motif, were recovered in recurrent prostate cancer samples. We now provide evidence that these clinically isolated substitutions lead to a partial loss of SC motif function and AR SUMOylation that affects multiple endogenous genes. Consistent with a structural role as terminators of secondary structure elements, substitution of Pro-390 by Gly fully supports both SC motif function and SUMOylation. As predicted from the functional properties of SC motifs, the clinically isolated mutations preferentially enhance transcription driven by genomic regions harboring multiple AR binding sites. The data support the view that alterations in AR SUMOylation play significant roles in AR-based diseases and offer novel SUMO-based therapeutic opportunities.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.