ArticleThe Journal of biological chemistry2015
Proteasome-mediated proteolysis of the polyglutamine-expanded androgen receptor is a late event in spinal and bulbar muscular atrophy (SBMA) pathogenesis.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Polyglutamine expansion induced dynamic misfolding of androgen receptor.Protein science : a publication of the Protein Society · 2025Article
- 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
- Neuromuscular junction pathology is correlated with differential motor unit vulnerability in spinal and bulbar muscular atrophy.Acta neuropathologica communications · 2022Article
- The role of ubiquitination in spinal and bulbar muscular atrophy.Frontiers in molecular neuroscience · 2022Review
- Deubiquitinase USP7 contributes to the pathogenicity of spinal and bulbar muscular atrophy.The Journal of clinical investigation · 2021Article
- Cell-Clearing Systems Bridging Repeat Expansion Proteotoxicity and Neuromuscular Junction Alterations in ALS and SBMA.International journal of molecular sciences · 2020Review
- Molecular Mechanisms and Therapeutics for SBMA/Kennedy's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Review
- Impaired Nuclear Export of Polyglutamine-Expanded Androgen Receptor in Spinal and Bulbar Muscular Atrophy.Scientific reports · 2019Article
- Inhibition of retrograde transport modulates misfolded protein accumulation and clearance in motoneuron diseases.Autophagy · 2017Article
- Chaperones in Polyglutamine Aggregation: Beyond the Q-Stretch.Frontiers in neuroscience · 2017Review
- The 11S Proteasomal Activator REGγ Impacts Polyglutamine-Expanded Androgen Receptor Aggregation and Motor Neuron Viability through Distinct Mechanisms.Frontiers in molecular neuroscience · 2017Article
- The Role of the Protein Quality Control System in SBMA.Journal of molecular neuroscience : MN · 2016Review
- Preventing the Androgen Receptor N/C Interaction Delays Disease Onset in a Mouse Model of SBMA.Cell reports · 2015Article
- Identification of novel polyglutamine-expanded aggregation species in spinal and bulbar muscular atrophy.Brain research · 2015Article
- Aberrant Autophagic Response in The Muscle of A Knock-in Mouse Model of Spinal and Bulbar Muscular Atrophy.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Proteolysis of polyglutamine-expanded proteins is thought to be a required step in the pathogenesis of several neurodegenerative diseases. The accepted view for many polyglutamine proteins is that proteolysis of the mutant protein produces a "toxic fragment" that induces neuronal dysfunction and death in a soluble form; toxicity of the fragment is buffered by its incorporation into amyloid-like inclusions. In contrast to this view, we show that, in the polyglutamine disease spinal and bulbar muscular atrophy, proteolysis of the mutant androgen receptor (AR) is a late event. Immunocytochemical and biochemical analyses revealed that the mutant AR aggregates as a full-length protein, becoming proteolyzed to a smaller fragment through a process requiring the proteasome after it is incorporated into intranuclear inclusions. Moreover, the toxicity-predicting conformational antibody 3B5H10 bound to soluble full-length AR species but not to fragment-containing nuclear inclusions. These data suggest that the AR is toxic as a full-length protein, challenging the notion of polyglutamine protein fragment-associated toxicity by redefining the role of AR proteolysis in spinal and bulbar muscular atrophy 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.