ArticleeLife2020
Inflammatory osteolysis is regulated by site-specific ISGylation of the scaffold protein NEMO.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 25 citations in OpenAlex.
- ISG15 Is a Key Multidirectional Regulator of Cytosolic RNA- and DNA-Sensing Pathways and Type I Interferon Feedback Loops.International journal of molecular sciences · 2026Review
- Interferon-JAK-STAT Axis in Bone Metabolism.Current osteoporosis reports · 2026Review
- Critical signaling pathways in osteoclast differentiation and bone resorption: mechanisms and therapeutic implications for periprosthetic osteolysis.Frontiers in cell and developmental biology · 2025Review
- DNA hypomethylation ameliorates erosive inflammatory arthritis by modulating interferon regulatory factor-8.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- MAVRIC based T2 mapping assessment of infrapatellar fat pad scarring in patients with total knee arthroplasty.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023Article
- ISGylation of NF-κBp65 by SCFArteriosclerosis, thrombosis, and vascular biology · 2023Article
- STING-dependent interferon signatures restrict osteoclast differentiation and bone loss in mice.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Biomolecular condensates: Formation mechanisms, biological functions, and therapeutic targets.MedComm · 2023Review
- The Functional Roles of ISG15/ISGylation in Cancer.Molecules (Basel, Switzerland) · 2023Review
- The dual role of autophagy in periprosthetic osteolysis.Frontiers in cell and developmental biology · 2023Review
- The diverse repertoire of ISG15: more intricate than initially thought.Experimental & molecular medicine · 2022Review
- Article
- Liquid phase separation of NEMO induced by polyubiquitin chains activates NF-κB.Molecular cell · 2022Article
- Mediators of Inflammation in Bone Physiology and Diseases.Mediators of inflammation · 2022Article
- Enzymatic Machinery of Ubiquitin and Ubiquitin-Like Modification Systems in Chondrocyte Homeostasis and Osteoarthritis.Current rheumatology reports · 2021Review
- The circular RNA circSlc7a11 promotes bone cancer pain pathogenesis in rats by modulating LLC-WRC 256 cell proliferation and apoptosis.Molecular and cellular biochemistry · 2021Article
- Inflammatory osteolysis is regulated by site-specific ISGylation of the scaffold protein NEMO.eLife · 2020Article
- Communications Between Bone Marrow Macrophages and Bone Cells in Bone Remodeling.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Inflammatory osteolysis is governed by exacerbated osteoclastogenesis. Ample evidence points to central role of NF-κB in such pathologic responses, yet the precise mechanisms underpinning specificity of these responses remain unclear. We propose that motifs of the scaffold protein IKKγ/NEMO partly facilitate such functions. As proof-of-principle, we used site-specific mutagenesis to examine the role of NEMO in mediating RANKL-induced signaling in mouse bone marrow macrophages, known as osteoclast precursors. We identified lysine (K)270 as a target regulating RANKL signaling as K270A substitution results in exuberant osteoclastogenesis in vitro and murine inflammatory osteolysis in vivo. Mechanistically, we discovered that K270A mutation disrupts autophagy, stabilizes NEMO, and elevates inflammatory burden. Specifically, K270A directly or indirectly hinders binding of NEMO to ISG15, a ubiquitin-like protein, which we show targets the modified proteins to autophagy-mediated lysosomal degradation. Taken together, our findings suggest that NEMO serves as a toolkit to fine-tune specific signals in physiologic and pathologic conditions.
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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.