ArticleThe Journal of clinical investigation2015
Disrupting SUMOylation enhances transcriptional function and ameliorates polyglutamine androgen receptor-mediated disease.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 55 citations in OpenAlex.
- Targeting androgen receptor stability and degradation: approaches for developing a therapy for spinal and bulbar muscular atrophy.Cell communication and signaling : CCS · 2025Review
- Mutant androgen receptor induces neurite loss and senescence independently of ARE binding in a neuronal model of SBMA.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Differentially disrupted spinal cord and muscle energy metabolism in spinal and bulbar muscular atrophy.JCI insight · 2024Article
- Paradoxes of Cellular SUMOylation Regulation: A Role of Biomolecular Condensates?Pharmacological reviews · 2023Review
- GCN5 maintains muscle integrity by acetylating YY1 to promote dystrophin expression.The Journal of cell biology · 2022Article
- Exploring the Role of Posttranslational Modifications in Spinal and Bulbar Muscular Atrophy.Frontiers in molecular neuroscience · 2022Review
- Gene therapy with AR isoform 2 rescues spinal and bulbar muscular atrophy phenotype by modulating AR transcriptional activity.Science advances · 2021Article
- Deubiquitinase USP7 contributes to the pathogenicity of spinal and bulbar muscular atrophy.The Journal of clinical investigation · 2021Article
- Sumoylation of transcription factor ETV1 modulates its oncogenic potential in prostate cancer.International journal of clinical and experimental pathology · 2021Article
- MEF2 impairment underlies skeletal muscle atrophy in polyglutamine disease.Acta neuropathologica · 2020Article
- The first year.Acta neuropathologica · 2020Article
- Molecular Mechanisms and Therapeutics for SBMA/Kennedy's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Review
- Humanising the mouse genome piece by piece.Nature communications · 2019Review
- Lack of androgen receptor SUMOylation results in male infertility due to epididymal dysfunction.Nature communications · 2019Article
- Targeting AR-Beclin 1 complex-modulated growth factor signaling increases the antiandrogen Enzalutamide sensitivity to better suppress the castration-resistant prostate cancer growth.Cancer letters · 2019Article
- Polyglutamine Repeats in Neurodegenerative Diseases.Annual review of pathology · 2019Review
- Impaired Nuclear Export of Polyglutamine-Expanded Androgen Receptor in Spinal and Bulbar Muscular Atrophy.Scientific reports · 2019Article
- SUMOylation by SUMO2 is implicated in the degradation of misfolded ataxin-7 via RNF4 in SCA7 models.Disease models & mechanisms · 2019Article
- Androgen receptor polyglutamine expansion drives age-dependent quality control defects and muscle dysfunction.The Journal of clinical investigation · 2018Article
- Transcriptional Dysregulation and Post-translational Modifications in Polyglutamine Diseases: From Pathogenesis to Potential Therapeutic Strategies.Frontiers in molecular neuroscience · 2018Review
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12 authors at 2 institutions in 1 country.
Funding
Abstract
Expansion of the polyglutamine (polyQ) tract within the androgen receptor (AR) causes neuromuscular degeneration in individuals with spinobulbar muscular atrophy (SBMA). PolyQ AR has diminished transcriptional function and exhibits ligand-dependent proteotoxicity, features that have both been implicated in SBMA; however, the extent to which altered AR transcriptional function contributes to pathogenesis remains controversial. Here, we sought to dissociate effects of diminished AR function from polyQ-mediated proteotoxicity by enhancing the transcriptional activity of polyQ AR. To accomplish this, we bypassed the inhibitory effect of AR SUMOylation (where SUMO indicates small ubiquitin-like modifier) by mutating conserved lysines in the polyQ AR that are sites of SUMOylation. We determined that replacement of these residues by arginine enhances polyQ AR activity as a hormone-dependent transcriptional regulator. In a murine model, disruption of polyQ AR SUMOylation rescued exercise endurance and type I muscle fiber atrophy; it also prolonged survival. These changes occurred without overt alterations in polyQ AR expression or aggregation, revealing the favorable trophic support exerted by the ligand-activated receptor. Our findings demonstrate beneficial effects of enhancing the transcriptional function of the ligand-activated polyQ AR and indicate that the SUMOylation pathway may be a potential target for therapeutic intervention in SBMA.
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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.