ArticleJournal of molecular neuroscience : MN2013
Inhibition of autophagy via p53-mediated disruption of ULK1 in a SCA7 polyglutamine disease model.
Article in Journal of molecular neuroscience : MN, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- Autophagy at the Crossroads of Protein and RNA Toxicity in Repeat Expansion Cerebellar Ataxias.Cells · 2026Review
- Molecular hallmarks of neurodegeneration in polyglutamine spinocerebellar ataxias.Cell death & disease · 2025Review
- Decoding the dual role of autophagy in cancer through transcriptional and epigenetic regulation.FEBS letters · 2025Review
- In Silico Analysis of miRNA-Regulated Pathways in Spinocerebellar Ataxia Type 7.Current issues in molecular biology · 2025Article
- Enhanced Sensitivity of A549 Cells to Doxorubicin with WSInternational journal of molecular sciences · 2024Article
- Natural products targeting autophagy and apoptosis in NSCLC: a novel therapeutic strategy.Frontiers in oncology · 2024Review
- Key Modulators of the Stress Granule Response TIA1, TDP-43, and G3BP1 Are Altered by Polyglutamine-Expanded ATXN7.Molecular neurobiology · 2022Article
- ULK overexpression mitigates motor deficits and neuropathology in mouse models of Machado-Joseph disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- The crosstalk among autophagy, apoptosis, and pyroptosis in cardiovascular disease.Frontiers in cardiovascular medicine · 2022Review
- Cell Survival and Cell Death at the Intersection of Autophagy and Apoptosis: Implications for Current and Future Cancer Therapeutics.ACS pharmacology & translational science · 2021Review
- Over Fifty Years of Life, Death, and Cannibalism: A Historical Recollection of Apoptosis and Autophagy.International journal of molecular sciences · 2021Review
- The role of cell signaling in the crosstalk between autophagy and apoptosis in the regulation of tumor cell survival in response to sorafenib and neratinib.Seminars in cancer biology · 2020Review
- Mitophagy and DNA damage signaling in human aging.Mechanisms of ageing and development · 2020Review
- Consensus Paper. Cerebellar Reserve: From Cerebellar Physiology to Cerebellar Disorders.Cerebellum (London, England) · 2020Review
- Molecular Targets and Therapeutic Strategies in Spinocerebellar Ataxia Type 7.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Review
- The Role of p53 in Determining Mitochondrial Adaptations to Endurance Training in Skeletal Muscle.Scientific reports · 2018Article
- Ulk1/FUNDC1 Prevents Nerve Cells from Hypoxia-Induced Apoptosis by Promoting Cell Autophagy.Neurochemical research · 2018Article
- Article
- Crosstalk Between Apoptosis and Autophagy: Environmental Genotoxins, Infection, and Innate Immunity.Journal of cell death · 2017Review
- Crosstalk Between Macroautophagy and Chaperone-Mediated Autophagy: Implications for the Treatment of Neurological Diseases.Molecular neurobiology · 2015Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spinocerebellar ataxia type 7 (SCA7) is one of nine neurodegenerative disorders caused by expanded polyglutamine domains. These so-called polyglutamine (polyQ) diseases are all characterized by aggregation. Reducing the level of aggregating polyQ proteins via pharmacological activation of autophagy has been suggested as a therapeutic approach. However, recently, evidence implicating autophagic dysfunction in these disorders has also been reported. In this study, we show that the SCA7 polyglutamine protein ataxin-7 (ATXN7) reduces the autophagic activity via a previously unreported mechanism involving p53-mediated disruption of two key proteins involved in autophagy initiation. We show that in mutant ATXN7 cells, an increased p53-FIP200 interaction and co-aggregation of p53-FIP200 into ATXN7 aggregates result in decreased soluble FIP200 levels and subsequent destabilization of ULK1. Together, this leads to a decreased capacity for autophagy induction via the ULK1-FIP200-Atg13-Atg101 complex. We also show that treatment with a p53 inhibitor, or a blocker of ATXN7 aggregation, can restore the soluble levels of FIP200 and ULK1, as well as increase the autophagic activity and reduce ATXN7 toxicity. Understanding the mechanism behind polyQ-mediated inhibition of autophagy is of importance if therapeutic approaches based on autophagy stimulation should be developed for these disorders.
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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.