ArticleBMC biology2010
Spartin activates atrophin-1-interacting protein 4 (AIP4) E3 ubiquitin ligase and promotes ubiquitination of adipophilin on lipid droplets.
Article in BMC biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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55 citing papers in PubMed, 95 citations in OpenAlex.
- A tale of dual role: HECT‑type E3 ubiquitin ligase mechanisms in liver diseases (Review).International journal of molecular medicine · 2026Review
- Lipid droplets in neurodegenerative diseases: pathological drivers and therapeutic vulnerabilities.Cell death discovery · 2026Review
- Hepatitis C virus NS3/4A protease cleaves SPG20, a key regulator of lipid droplet turnover, to promote lipid droplet formation.Journal of virology · 2025Article
- How to Reproduce in the Siberian Winter: Proteome Dynamics Reveals the Timing of Reproduction-Related Processes in an Amphipod Species Endemic to Lake Baikal.Ecology and evolution · 2025Article
- The emerging role of E3 ubiquitin ligases and deubiquitinases in metabolic dysfunction-associated steatotic liver disease.Journal of translational medicine · 2025Review
- Ubiquitination in lipid metabolism reprogramming: implications for pediatric solid tumors.Frontiers in immunology · 2025Review
- TRIB3 promotes the progression of renal cell carcinoma by upregulating the lipid droplet-associated protein PLIN2.Cell death & disease · 2024Article
- Feedback regulation of ubiquitination and phase separation of HECT E3 ligases.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Review
- PRMT5 epigenetically regulates the E3 ubiquitin ligase ITCH to influence lipid accumulation during mycobacterial infection.PLoS pathogens · 2022Article
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- Lipophagy at a glance.Journal of cell science · 2022Article
- Hereditary Spastic Paraplegia: An Update.International journal of molecular sciences · 2022Review
- Review
- Ubiquitinated ligation protein NEDD4L participates in MiR-30a-5p attenuated atherosclerosis by regulating macrophage polarization and lipid metabolism.Molecular therapy. Nucleic acids · 2021Article
- Methylation as a critical epigenetic process during tumor progressions among Iranian population: an overview.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2021Review
- ACSS3 represses prostate cancer progression through downregulating lipid droplet-associated protein PLIN3.Theranostics · 2021Article
- Lipid Droplets in the Pathogenesis of Hereditary Spastic Paraplegia.Frontiers in molecular biosciences · 2021Review
- Hereditary Spastic Paraplegia and Future Therapeutic Directions: Beneficial Effects of Small Compounds Acting on Cellular Stress.Frontiers in neuroscience · 2021Review
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5 authors at 2 institutions in 1 country.
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Abstract
backgroundSpartin protein is involved in degradation of epidermal growth factor receptor and turnover of lipid droplets and a lack of expression of this protein is responsible for hereditary spastic paraplegia type 20 (SPG20). Spartin is a multifunctional protein that associates with many cellular organelles, including lipid droplets. Recent studies showed that spartin interacts with E3 ubiquitin ligases that belong to the neural precursor cell-expressed developmentally downregulated gene (Nedd4) family, including atrophin-1-interacting protein 4 (AIP4/ITCH). However, the biological importance of the spartin-AIP4 interaction remains unknown.
resultsIn this study, we show that spartin is not a substrate for AIP4 activity and that spartin's binding to AIP4 significantly increases self-ubiquitination of this E3 ligase, indicating that spartin disrupts the AIP4 autoinhibitory intramolecular interaction. Correspondingly, spartin has a seven times higher binding affinity to the WW region of AIP4 than the binding of the WW region has to the catalytic homologues of the E6-associated protein C-terminus (HECT) domain, as measured by enzyme-linked immunosorbent assay. We also show that spartin recruits AIP4 to lipid droplets and promotes ubiquitination of lipid droplet-associated protein, adipophilin, which regulates turnover of lipid droplets.
conclusionsOur findings demonstrate that spartin acts as an adaptor protein that activates and recruits AIP4 E3 ubiquitin ligase to lipid droplets and by this means regulates the level of ubiquitination of adipophilin and potentially other lipid-associated proteins. We propose that this is one of the mechanisms by which spartin regulates lipid droplet turnover and might contribute to the pathology of SPG20.
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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.