ArticleScientific reports2014
Ubiquitin ligase ITCH recruitment suppresses the aggregation and cellular toxicity of cytoplasmic misfolded proteins.
Article in Scientific reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- The role of HECT-type E3 ubiquitin ligases in DNA damage response and repair.Cell death discovery · 2025Review
- ATXN3: a multifunctional protein involved in the polyglutamine disease spinocerebellar ataxia type 3.Expert reviews in molecular medicine · 2024Review
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- The role of NEDD4 related HECT-type E3 ubiquitin ligases in defective autophagy in cancer cells: molecular mechanisms and therapeutic perspectives.Molecular medicine (Cambridge, Mass.) · 2023Review
- The Josephin domain (JD) containing proteins are predicted to bind to the same interactors: Implications for spinocerebellar ataxia type 3 (SCA3) studies usingFrontiers in molecular neuroscience · 2023Article
- Enzymatic analysis of WWP2 E3 ubiquitin ligase using protein microarrays identifies autophagy-related substrates.The Journal of biological chemistry · 2022Article
- The Roles of NEDD4 Subfamily of HECT E3 Ubiquitin Ligases in Neurodevelopment and Neurodegeneration.International journal of molecular sciences · 2022Review
- Ubr1-induced selective endophagy/autophagy protects against the endosomal and CaCellular and molecular life sciences : CMLS · 2022Article
- Attenuation of HECT-E3 ligase expression rescued memory deficits in 3xTg-AD mice.Frontiers in aging neuroscience · 2022Article
- Praja1 ubiquitin ligase facilitates degradation of polyglutamine proteins and suppresses polyglutamine-mediated toxicity.Molecular biology of the cell · 2021Article
- A fine balance between Prpf19 and Exoc7 in achieving degradation of aggregated protein and suppression of cell death in spinocerebellar ataxia type 3.Cell death & disease · 2021Article
- ITCH as a potential therapeutic target in human cancers.Seminars in cancer biology · 2020Review
- Discovery of a potent small molecule inhibiting Huntington's disease (HD) pathogenesis via targeting CAG repeats RNA and Poly Q protein.Scientific reports · 2019Article
- Emerging roles of HECT-type E3 ubiquitin ligases in autophagy regulation.Molecular oncology · 2019Review
- Global Proteome and Ubiquitinome Changes in the Soluble and Insoluble Fractions of Q175 Huntington Mice Brains.Molecular & cellular proteomics : MCP · 2019Article
- Lanosterol Suppresses the Aggregation and Cytotoxicity of Misfolded Proteins Linked with Neurodegenerative Diseases.Molecular neurobiology · 2018Article
- Dynamic recruitment of ubiquitin to mutant huntingtin inclusion bodies.Scientific reports · 2018Article
- E3 Ubiquitin Ligases Neurobiological Mechanisms: Development to Degeneration.Frontiers in molecular neuroscience · 2017Review
- Ibuprofen Induces Mitochondrial-Mediated Apoptosis Through Proteasomal Dysfunction.Molecular neurobiology · 2016Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The protein quality control (QC) system protects cells against cellular toxicity induced by misfolded proteins and maintains overall cellular fitness. Inefficient clearance of or failure to degrade damaged proteins causes several diseases, especially age-linked neurodegenerative disorders. Attenuation of misfolded protein degradation under severe stress conditions leads to the rapid over-accumulation of toxic proteinaceous aggregates in the cytoplasmic compartment. However, the precise cytoplasmic quality control degradation mechanism is unknown. In the present study, we demonstrate that the Nedd4-like E3 ubiquitin ligase ITCH specifically interacts with mutant bona fide misfolded proteins and colocalizes with their perinuclear aggregates. In a cell culture model, we demonstrate ITCH recruitment by cytoplasmic inclusions containing polyglutamine-expanded huntingtin or ataxin-3 proteins. Transient overexpression of ITCH dramatically induced the degradation of thermally denatured misfolded luciferase protein. Partial depletion of ITCH increased the rate of aggregate formation and cell death generated by expanded polyglutamine proteins. Finally, we demonstrate that overexpression of ITCH alleviates the cytotoxic potential of expanded polyglutamine proteins and reduces aggregation. These observations indicate that ITCH is involved in the cytosolic quality control pathway and may help to explain how abnormal proteins are targeted by QC ubiquitin-protein ligases.
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