ArticleThe Journal of biological chemistry2013
ISG15 deregulates autophagy in genotoxin-treated ataxia telangiectasia cells.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Autophagy-related genes polymorphism in hepatitis B virus-associated hepatocellular carcinoma: A systematic review.Immunity, inflammation and disease · 2024Pooled it
- In vivo effects of dexamethasone on blood gene expression in ataxia telangiectasia.Molecular and cellular biochemistry · 2018Trial
- Organelle-centered ISG15 biology: distinguishing covalent ISGylation from interferon-associated responses.Frontiers in immunology · 2026Review
- Interferon-induced protein ISG15 in the central nervous system, quo vadis?FEBS letters · 2025Review
- Molecular Interplay of ISG15/ISGylation in Neuropathologies.CNS & neurological disorders drug targets · 2025Review
- Dynamic molecular network analysis of iPSC-Purkinje cells differentiation delineates roles of ISG15 in SCA1 at the earliest stage.Communications biology · 2024Article
- ISG15 Is a Novel Regulator of Lipid Metabolism duringMicrobiology spectrum · 2022Article
- The diverse repertoire of ISG15: more intricate than initially thought.Experimental & molecular medicine · 2022Review
- ISGylation is induced in neurons by demyelination driving ISG15-dependent microglial activation.Journal of neuroinflammation · 2022Article
- Transcriptomic characterization of tissues from patients and subsequent pathway analyses reveal biological pathways that are implicated in spastic ataxia.Cell & bioscience · 2022Article
- ISG15 and ISGylation in Human Diseases.Cells · 2022Review
- Temporal Cortex Microarray Analysis Revealed Impaired Ribosomal Biogenesis and Hyperactivity of the Glutamatergic System: An Early Signature of Asymptomatic Alzheimer's Disease.Frontiers in neuroscience · 2022Article
- ATM loss disrupts the autophagy-lysosomal pathway.Autophagy · 2021Article
- Review
- A Critical Role for ISGylation, Ubiquitination and, SUMOylation in Brain Damage: Implications for Neuroprotection.Neurochemical research · 2020Review
- Hydroxycamptothecin mediates antiproliferative effects through apoptosis and autophagy in A549 cells.Oncology letters · 2018Article
- Identification of differentially expressed genes and regulatory relationships in Huntington's disease by bioinformatics analysis.Molecular medicine reports · 2018Article
- Regulation of mitophagy by the ubiquitin pathway in neurodegenerative diseases.Experimental biology and medicine (Maywood, N.J.) · 2018Review
- The Thr300Ala variant of ATG16L1 is associated with decreased risk of brain metastasis in patients with non-small cell lung cancer.Autophagy · 2017Article
- Identification and characterization of a novel ISG15-ubiquitin mixed chain and its role in regulating protein homeostasis.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Ataxia-telangiectasia (A-T) is a cerebellar neurodegenerative disorder; however, the basis for the neurodegeneration in A-T is not well established. Lesions in the ubiquitin and autophagy pathways are speculated to contribute to the neurodegeneration in other neurological diseases and may have a role in A-T neurodegeneration. Our recent studies revealed that the constitutively elevated ISG15 pathway impairs targeted proteasome-mediated protein degradation in A-T cells. Here, we demonstrate that the basal autophagy pathway is activated in the ubiquitin pathway-compromised A-T cells. We also show that genotoxic stress triggers aberrant degradation of the proteasome and autophagy substrates (autophagic flux) in A-T cells. Inhibition of autophagy at an early stage using 3-methyladenine blocked UV-induced autophagic flux in A-T cells. On the other hand, bafilomycin A1, which inhibits autophagy at a late stage, failed to block UV-induced autophagic flux, suggesting that overinduction of autophagy may underlie aberrant autophagic flux in A-T cells. The ISG15-specific shRNA that restored proteasome function restores autophagic function in A-T cells. These findings suggest that autophagy compensates for the ISG15-dependent ablation of proteasome-mediated protein degradation in A-T cells. Genotoxic stress overactivates this compensatory mechanism, triggering aberrant autophagic flux in A-T cells. Supporting the model, we show that autophagy is activated in the brain tissues of human A-T patients. This highlights a plausible causal contribution of a novel "ISG15 proteinopathy" in A-T neuronal cell death.
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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.