ArticleProceedings of the National Academy of Sciences of the United States of America2014
SUMOylation at K340 inhibits tau degradation through deregulating its phosphorylation and ubiquitination.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers.
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Who cites it
143 citing papers in PubMed, 221 citations in OpenAlex.
- The role of SUMOylation in regulating proteins that drive neuronal disease progression.Biochemistry and biophysics reports · 2026Review
- Advances in Alzheimer's disease: mechanistic insights and therapeutic targets.Science China. Life sciences · 2026Review
- Tau physiology and pathology: impacts on cellular structures and neurodegenerative diseases.Inflammopharmacology · 2026Review
- PIAS1-mediated GSK3β SUMOylation exacerbates tauopathy and cognitive deficits in Alzheimer's disease models.Molecular psychiatry · 2026Article
- SUMOylation in Mitochondrial Quality Control: Mechanisms and Implications for Neurodegenerative Disease.Molecular neurobiology · 2026Review
- MicroRNA-181 influences Alzheimer's risk by regulating neprilysin and microtubule-associated tau pathways, offering a novel target.bioRxiv : the preprint server for biology · 2026Article
- Biophysical assessment of the molecular mechanisms of Tau aggregation and its role in Alzheimer's disease.Protein science : a publication of the Protein Society · 2026Review
- Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease.bioRxiv : the preprint server for biology · 2026Article
- Review
- The modifier matrix: emerging roles of ubiquitin-like proteins in Alzheimer's disease.Molecular neurodegeneration advances · 2026Review
- Ubiquitin signatures on aggregating proteins in neurodegeneration.Essays in biochemistry · 2025Review
- Tau protein: Physiological functions and multifaceted roles in neurodegenerative and psychiatric disorders.Genomic psychiatry : advancing science from genes to society · 2025Article
- Death-associated protein kinase 1-dependent SENP1 degradation increases tau SUMOylation and leads to cognitive dysfunction in a mouse model for tauopathy.Molecular neurodegeneration · 2025Article
- PIAS1/PIAS4-Mediated SUMOylation of TDP-43 Is Induced by Oxidative Stress.bioRxiv : the preprint server for biology · 2025Article
- Current Understanding of Protein Aggregation in Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- APP SUMOylation prevents BACE1 cleavage of APP and increases BACE1 degradation to promote the nonamyloidogenic pathway.Molecular medicine (Cambridge, Mass.) · 2025Article
- Alzheimer's Disease: From Molecular Mechanisms to Promising Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Polyamination with spermidine enhances pathogenic tau conformations while reducing filamentous aggregate formation in vitro.The Biochemical journal · 2025Article
- Molecular signatures of regional vulnerability to tauopathy in excitatory cortical neurons.Acta neuropathologica · 2025Article
- Cytoskeletal Proteins and Alzheimer's Disease Pathogenesis: Focusing on the Interplay with Tau Pathology.Biomolecules · 2025Review
83 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Intracellular accumulation of the abnormally modified tau is hallmark pathology of Alzheimer's disease (AD), but the mechanism leading to tau aggregation is not fully characterized. Here, we studied the effects of tau SUMOylation on its phosphorylation, ubiquitination, and degradation. We show that tau SUMOylation induces tau hyperphosphorylation at multiple AD-associated sites, whereas site-specific mutagenesis of tau at K340R (the SUMOylation site) or simultaneous inhibition of tau SUMOylation by ginkgolic acid abolishes the effect of small ubiquitin-like modifier protein 1 (SUMO-1). Conversely, tau hyperphosphorylation promotes its SUMOylation; the latter in turn inhibits tau degradation with reduction of solubility and ubiquitination of tau proteins. Furthermore, the enhanced SUMO-immunoreactivity, costained with the hyperphosphorylated tau, is detected in cerebral cortex of the AD brains, and β-amyloid exposure of rat primary hippocampal neurons induces a dose-dependent SUMOylation of the hyperphosphorylated tau. Our findings suggest that tau SUMOylation reciprocally stimulates its phosphorylation and inhibits the ubiquitination-mediated tau degradation, which provides a new insight into the AD-like tau accumulation.
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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.