ArticleCell death discovery2019
TRIAD3/RNF216 E3 ligase specifically synthesises K63-linked ubiquitin chains and is inactivated by mutations associated with Gordon Holmes syndrome.
Article in Cell death discovery, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- Substrate Profiling of RNF216 Uncovers a Translation-Linked OTUD4 Regulatory Axis.bioRxiv : the preprint server for biology · 2026Article
- Human Gordon Holmes Syndrome modeling in mice reveals essential function of RNF216 ubiquitination in spermatogenesis and male fertility.Genes & diseases · 2026Article
- NPRL2 restricts porcine reproductive and respiratory syndrome virus replication by targeting viral Nsp1α for autophagic degradation.Veterinary research · 2026Article
- RNF216 as a Promising Biomarker for Prognosis, Immunotherapy, and Chemotherapy in LIHC: A Comprehensive Pan-Cancer Analysis and Experimental Validation.Journal of Cancer · 2026Article
- The autophagy adaptor TRIAD3A promotes tau fibrillation by nested phase separation.Nature cell biology · 2024Article
- The E3 ubiquitin ligase RNF216 contains a linear ubiquitin chain-determining-like domain that functions to regulate dendritic arborization and dendritic spine type in hippocampal neurons.bioRxiv : the preprint server for biology · 2023Article
- The unifying catalytic mechanism of the RING-between-RING E3 ubiquitin ligase family.Nature communications · 2023Article
- The E3 ubiquitin ligase RNF216/TRIAD3 is a key coordinator of the hypothalamic-pituitary-gonadal axis.iScience · 2022Article
- Chain reactions: molecular mechanisms of RBR ubiquitin ligases.Biochemical Society transactions · 2020Review
- New roles for the de-ubiquitylating enzyme OTUD4 in an RNA-protein network and RNA granules.Journal of cell science · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TRIAD3/RNF216 is a ubiquitin ligase of the RING-in-between-RING family. Recent publications identified TRIAD3 mutations in patients with neurological diseases, including Gordon Holmes syndrome and Huntington-like disorder. To understand the functional relevance of these disease-associated mutations, we have tested the ubiquitin ligase activity of mutated TRIAD3 in vitro. Several of these point mutations completely abrogated TRIAD3's catalytic activity. Using mass spectrometry, we identified new TRIAD3-interacting proteins/substrates from mouse brain lysate, which provide a new link between TRIAD3 and processes involving clathrin-mediated endocytosis. Strikingly, we found that TRIAD3 synthesises specifically lysine-63 (K63)-linked poly-ubiquitin chains in vitro, a chain type that usually plays a role in mediating signalling events rather than triggering proteasomal degradation. Therefore, this finding is of great importance to further understand TRIAD3's cellular role and loss-of-function in disease.
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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.