ArticleProceedings of the National Academy of Sciences of the United States of America2008
Deficiency in ubiquitin ligase TRIM2 causes accumulation of neurofilament light chain and neurodegeneration.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
88 citing papers in PubMed, 142 citations in OpenAlex.
- Neuroprotective Role of E3 Ubiquitin Ligase TRIM2 in Parkinson's Disease: Attenuation of Oxidative Stress and Apoptosis via Promoting ELAVL1 Ubiquitination.CNS neuroscience & therapeutics · 2026Article
- Junctions in Jeopardy: the neuromuscular junction is a selective pathological target in Charcot-Marie-Tooth disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Integrated multi-omics analysis and functional validation reveal the role of TRIM2 as a potential novel biomarker in breast cancer.Breast cancer research : BCR · 2026Article
- BCOR Mutations Deregulate Cell Cycle and Hypoxic Adaptation Pathways in Retinoblastoma.Molecular cancer research : MCR · 2026Article
- Sex- and brain region-specific gene expression in Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2026Article
- Allele-specific splicing modulates protein isoforms and Alzheimer's risk.bioRxiv : the preprint server for biology · 2026Article
- TRIM2 E3 ligase substrate discovery reveals zinc-mediated regulation of TMEM106B in the endolysosomal pathway.EMBO reports · 2026Article
- TRIM2 suppresses prostate cancer progression by promoting ubiquitin-mediated degradation of DTNBP1.Frontiers in molecular biosciences · 2026Article
- Long-term atorvastatin improves cognitive function by modulating SIRT2-mediated dynamic transition of NFL lysine 272 crotonylation to ubiquitination in naturally aging rats.Cell death discovery · 2025Article
- Ubiquitin-Proteasome System Dysregulation in Alzheimer's Disease Impacts Protein Abundance.bioRxiv : the preprint server for biology · 2025Article
- Identification of RING E3 pseudoligases in the TRIM protein family.Nature communications · 2025Article
- TRIM2: a double-edged sword preventing apoptosis.The FEBS journal · 2025Article
- Tripartite motif 2b (Journal of virology · 2024Article
- Neurofilament Biophysics: From Structure to Biomechanics.Molecular biology of the cell · 2024Review
- TRIM2 Selectively Regulates Inflammation-Driven Pathological Angiogenesis without Affecting Physiological Hypoxia-Mediated Angiogenesis.International journal of molecular sciences · 2024Article
- Microtubule association of TRIM3 revealed by differential extraction proteomics.Journal of cell science · 2024Article
- The CRL3Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Tripartite Motif Protein Family in Central Nervous System Diseases.Cellular and molecular neurobiology · 2023Review
- Central Nervous System Targeted Protein Degraders.Biomolecules · 2023Review
- It's a TRIM-endous view from the top: the varied roles of TRIpartite Motif proteins in brain development and disease.Frontiers in molecular neuroscience · 2023Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
Abstract
TRIM RING finger proteins have been shown to play an important role in cancerogenesis, in the pathogenesis of some human hereditary disorders, and in the defense against viral infection, but the function of the majority of TRIM proteins remains unknown. Here, we show that TRIM RING finger protein TRIM2, highly expressed in the nervous system, is an UbcH5a-dependent ubiquitin ligase. We further demonstrate that TRIM2 binds to neurofilament light subunit (NF-L) and regulates NF-L ubiquitination. Additionally, we show that mice deficient in TRIM2 have increased NF-L level in axons and NF-L-filled axonal swellings in cerebellum, retina, spinal cord, and cerebral cortex. The axonopathy is followed by progressive neurodegeneration accompanied by juvenile-onset tremor and ataxia. Our results demonstrate that TRIM2 is an ubiquitin ligase and point to a mechanism regulating NF-L metabolism through an ubiquitination pathway that, if deregulated, triggers neurodegeneration.
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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.