ArticleNature communications2016
Linear ubiquitination is involved in the pathogenesis of optineurin-associated amyotrophic lateral sclerosis.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 142 citations in OpenAlex.
- Mechanism of K63-linked polyubiquitin recognition and cleavage by the BRCA1-A complex.Nature communications · 2026Article
- Cosolutes Modulate Polyubiquitin Fibrillation.ACS omega · 2026Article
- Article
- TBK1 Induces the Formation of Optineurin Filaments That Condensate with Polyubiquitin and LC3 for Cargo Sequestration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting mitochondria for the treatment of neurodegenerative diseases.Frontiers in neuroscience · 2026Review
- The Ubiquitin Script: writing protein fates in chains.Essays in biochemistry · 2025Review
- Structural and Functional Perspectives of Optineurin in Autophagy, Immune Signaling, and Cancer.Cells · 2025Review
- Optineurin is an adaptor protein for ubiquitinated substrates in Golgi membrane-associated degradation.Nature communications · 2025Article
- Review
- Deciphering Key Regulatory Roles of Linear Ubiquitination in Cell Fate Determination and Disease.Research (Washington, D.C.) · 2025Review
- HACE1 as a bridge between oxidative stress and autophagy.Frontiers in immunology · 2025Review
- LUBAC enables tumor-promoting LTβ receptor signaling by activating canonical NF-κB.Cell death and differentiation · 2024Article
- Secondary interactions in ubiquitin-binding domains achieve linkage or substrate specificity.Cell reports · 2024Article
- Clinical heterogeneity within the ALS-FTD spectrum in a family with a homozygous optineurin mutation.Annals of clinical and translational neurology · 2024Article
- N4BP1 functions as a dimerization-dependent linear ubiquitin reader which regulates TNF signalling.Cell death discovery · 2024Article
- Optineurin provides a mitophagy contact site for TBK1 activation.The EMBO journal · 2024Article
- The mechanism of linear ubiquitination in regulating cell death and correlative diseases.Cell death & disease · 2023Review
- An interaction between OTULIN and SCRIB uncovers roles for linear ubiquitination in planar cell polarity.Disease models & mechanisms · 2023Article
- Ubiquitination detection techniques.Experimental biology and medicine (Maywood, N.J.) · 2023Review
- Emerging Trends in the Field of Inflammation and Proteinopathy in ALS/FTD Spectrum Disorder.Biomedicines · 2023Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Optineurin (OPTN) mutations cause neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and glaucoma. Although the ALS-associated E478G mutation in the UBAN domain of OPTN reportedly abolishes its NF-κB suppressive activity, the precise molecular basis in ALS pathogenesis still remains unclear. Here we report that the OPTN-UBAN domain is crucial for NF-κB suppression. Our crystal structure analysis reveals that OPTN-UBAN binds linear ubiquitin with homology to NEMO. TNF-α-mediated NF-κB activation is enhanced in OPTN-knockout cells, through increased ubiquitination and association of TNF receptor (TNFR) complex I components. Furthermore, OPTN binds caspase 8, and OPTN deficiency accelerates TNF-α-induced apoptosis by enhancing complex II formation. Immunohistochemical analyses of motor neurons from OPTN-associated ALS patients reveal that linear ubiquitin and activated NF-κB are partially co-localized with cytoplasmic inclusions, and that activation of caspases is elevated. Taken together, OPTN regulates both NF-κB activation and apoptosis via linear ubiquitin binding, and the loss of this ability may lead to ALS.
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