ArticleBiochimica et biophysica acta2014
Axotrophin/MARCH7 acts as an E3 ubiquitin ligase and ubiquitinates tau protein in vitro impairing microtubule binding.
Article in Biochimica et biophysica acta, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
36 citing papers in PubMed, 56 citations in OpenAlex.
- Disease-specific tau polymorphs are associated with unique protein networks across proteinopathies.The EMBO journal · 2026Article
- Review
- Distinct factors drive the progression of tau pathology in Alzheimer's disease.Fundamental research · 2026Review
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- Boosting Brain Clean-Up: Can Targeting UPS Genes Offer Neuroprotection?Molecular neurobiology · 2025Review
- Cytoskeletal Proteins and Alzheimer's Disease Pathogenesis: Focusing on the Interplay with Tau Pathology.Biomolecules · 2025Review
- Tau degradation in Alzheimer's disease: Mechanisms and therapeutic opportunities.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Alzheimer's disease: insights into pathology, molecular mechanisms, and therapy.Protein & cell · 2025Review
- Role of MARCH E3 ubiquitin ligases in cancer development.Cancer metastasis reviews · 2024Review
- Cellular and pathological functions of tau.Nature reviews. Molecular cell biology · 2024Review
- Targeting USP11 regulation by a novel lithium-organic coordination compound improves neuropathologies and cognitive functions in Alzheimer transgenic mice.EMBO molecular medicine · 2024Article
- The autophagy adaptor TRIAD3A promotes tau fibrillation by nested phase separation.Nature cell biology · 2024Article
- Oligodendrocyte Dysfunction in Tauopathy: A Less Explored Area in Tau-Mediated Neurodegeneration.Cells · 2024Review
- Post-Translational Modifications in Tau and Their Roles in Alzheimer's Pathology.Current Alzheimer research · 2024Review
- Article
- The Role of Post-Translational Modifications on the Structure and Function of Tau Protein.Journal of molecular neuroscience : MN · 2022Review
- Protein degradation-associated mechanisms that are affected in Alzheimer´s disease.Molecular and cellular biochemistry · 2022Review
- All Roads Lead to Rome: Different Molecular Players Converge to Common Toxic Pathways in Neurodegeneration.Cells · 2021Review
- Tau Protein Interaction Partners and Their Roles in Alzheimer's Disease and Other Tauopathies.International journal of molecular sciences · 2021Review
- Cereblon Regulates the Proteotoxicity of Tau by Tuning the Chaperone Activity of DNAJA1.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Tau is the major microtubule-associated protein in neurons involved in microtubule stabilization in the axonal compartment. Changes in tau gene expression, alternative splicing and posttranslational modification regulate tau function and in tauopathies can result in tau mislocalization and dysfunction, causing tau aggregation and cell death. To uncover proteins involved in the development of tauopathies, a yeast two-hybrid system was used to screen for tau-interacting proteins. We show that axotrophin/MARCH7, a RING-variant domain containing protein with similarity to E3 ubiquitin ligases interacts with tau. We defined the tau binding domain to amino acids 552-682 of axotrophin comprising the RING-variant domain. Co-immunoprecipitation and co-localization confirmed the specificity of the interaction. Intracellular localization of axotrophin is determined by an N-terminal nuclear targeting signal and a C-terminal nuclear export signal. In AD brain nuclear localization is lost and axotrophin is rather associated with neurofibrillary tangles. We find here that tau becomes mono-ubiquitinated by recombinant tau-interacting RING-variant domain, which diminishes its microtubule-binding. In vitro ubiquitination of four-repeat tau results in incorporation of up to four ubiquitin molecules compared to two molecules in three-repeat tau. In summary, we present a novel tau modification occurring preferentially on 4-repeat tau protein which modifies microtubule-binding and may impact on the pathogenesis of tauopathies.
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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.