ArticleNeuron2015
Protein arginine methyltransferase 6 enhances polyglutamine-expanded androgen receptor function and toxicity in spinal and bulbar muscular atrophy.
Article in Neuron, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- Discovery of novel ancestry specific genes for androgens and hypogonadism in Million Veteran Program Men.Nature communications · 2025Pooled it
- The alternative androgen receptor isoform A mitigates toxicity of polyglutamine-elongated mutant androgen receptor in spinal and bulbar muscular atrophy.Journal of advanced research · 2026Article
- Targeting the PRMT5/Nur77 methylation axis enhances endometrial decidualization capacity and female fertility in preclinical models.The Journal of clinical investigation · 2026Article
- Prmt6 Deficiency or Inhibition Restores Microglial Homeostasis and Promotes Scar-Limited Repair in Adult Spinal Cord Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Unveiling the effect of curcumin on ion channels of SBMA motoneuron-derived cells and human IPSC-derived neurons: initial electrophysiological findings.European biophysics journal : EBJ · 2026Article
- PRMT6 is required for initiating and amplifying macrophage-induced inflammation in heterotopic ossification by increasing CCL2 expression.Bone research · 2026Article
- The evolution of eukaryotic linear motifs governing the function of androgen receptor from fish to Homo sapiens.Nucleic acids research · 2025Article
- Protein Arginine Methyltransferases from Regulatory Function to Clinical Implication in Central Nervous System.Cellular and molecular neurobiology · 2025Review
- PRMT6 Epigenetically Drives Metabolic Switch from Fatty Acid Oxidation toward Glycolysis and Promotes Osteoclast Differentiation During Osteoporosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- 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
- Metabolomics of cerebrospinal fluid reveals candidate diagnostic biomarkers to distinguish between spinal muscular atrophy type II and type III.CNS neuroscience & therapeutics · 2024Article
- Prmt6 represses the pro-adipogenic Ppar-gamma-C/ebp-alpha transcription factor loop.Scientific reports · 2024Article
- A phenotypically robust model of spinal and bulbar muscular atrophy in Drosophila.Journal of neuroscience research · 2024Article
- PRMT inhibitor promotes SMN2 exon 7 inclusion and synergizes with nusinersen to rescue SMA mice.EMBO molecular medicine · 2023Article
- Arginine methylation of RNA-binding proteins is impaired in Huntington's disease.Human molecular genetics · 2023Article
- Critical Roles of Protein Arginine Methylation in the Central Nervous System.Molecular neurobiology · 2023Review
- Functional Implications of Protein Arginine Methyltransferases (PRMTs) in Neurodegenerative Diseases.Biology · 2023Review
- LSD1/PRMT6-targeting gene therapy to attenuate androgen receptor toxic gain-of-function ameliorates spinobulbar muscular atrophy phenotypes in flies and mice.Nature communications · 2023Article
- Antagonistic effect of cyclin-dependent kinases and a calcium-dependent phosphatase on polyglutamine-expanded androgen receptor toxic gain of function.Science advances · 2023Article
- Androgen receptor inhibits the hair follicle induction potential of dermal papilla cells by binding with Tcf4 at the A574 binding site.Genes & diseases · 2023Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 7 institutions in 3 countries.
Funding
Abstract
Polyglutamine expansion in androgen receptor (AR) is responsible for spinobulbar muscular atrophy (SBMA) that leads to selective loss of lower motor neurons. Using SBMA as a model, we explored the relationship between protein structure/function and neurodegeneration in polyglutamine diseases. We show here that protein arginine methyltransferase 6 (PRMT6) is a specific co-activator of normal and mutant AR and that the interaction of PRMT6 with AR is significantly enhanced in the AR mutant. AR and PRMT6 interaction occurs through the PRMT6 steroid receptor interaction motif, LXXLL, and the AR activating function 2 surface. AR transactivation requires PRMT6 catalytic activity and involves methylation of arginine residues at Akt consensus site motifs, which is mutually exclusive with serine phosphorylation by Akt. The enhanced interaction of PRMT6 and mutant AR leads to neurodegeneration in cell and fly models of SBMA. These findings demonstrate a direct role of arginine methylation in polyglutamine disease pathogenesis.
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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.