ArticleThe EMBO journal2009
NEMO specifically recognizes K63-linked poly-ubiquitin chains through a new bipartite ubiquitin-binding domain.
Article in The EMBO journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers.
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Who cites it
121 citing papers in PubMed, 194 citations in OpenAlex.
- Time-varying stimuli that prolong IKK activation promote nuclear remodeling and mechanistic switching of NF-κB dynamics.Nature communications · 2025Article
- Linear poly-ubiquitin remodels the proteome and influences hundreds of regulators in Drosophila.G3 (Bethesda, Md.) · 2024Article
- Age-related effects of optineurin deficiency in the mouse eye.Vision research · 2024Article
- HDX-MS Analysis of Catalytic Activation of IKK2 in the IκB Kinase Complex.Biochemistry · 2024Article
- Molecular mechanism of IKK catalytic dimer docking to NF-κB substrates.Nature communications · 2024Article
- Cellular heterogeneity in TNF/TNFR1 signalling: live cell imaging of cell fate decisions in single cells.Cell death & disease · 2024Review
- Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response.The EMBO journal · 2024Article
- NEMO reshapes the α-Synuclein aggregate interface and acts as an autophagy adapter by co-condensation with p62.Nature communications · 2023Article
- Damaged mitochondria recruit the effector NEMO to activate NF-κB signaling.Molecular cell · 2023Article
- New Insights into NF-κB Signaling in Innate Immunity: Focus on Immunometabolic Crosstalks.Biology · 2023Review
- Linear ubiquitination induces NEMO phase separation to activate NF-κB signaling.Life science alliance · 2023Article
- Ageing-Induced Decline in Primary Myeloid Cell Phagocytosis Is Unaffected by Optineurin Insufficiency.Biology · 2023Article
- Control of protein stability by post-translational modifications.Nature communications · 2023Review
- Optineurin Deficiency and Insufficiency Lead to Higher Microglial TDP-43 Protein Levels.International journal of molecular sciences · 2022Article
- Recycling and Reshaping-E3 Ligases and DUBs in the Initiation of T Cell Receptor-Mediated Signaling and Response.International journal of molecular sciences · 2022Review
- Genetically programmed alternative splicing of NEMO mediates an autoinflammatory disease phenotype.The Journal of clinical investigation · 2022Article
- Emerging Roles of Non-proteolytic Ubiquitination in Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
- Viruses utilize ubiquitination systems to escape TLR/RLR-mediated innate immunity.Frontiers in immunology · 2022Review
- The Nuclear Factor Kappa B (NF-kB) signaling in cancer development and immune diseases.Genes & diseases · 2021Review
- Role of UPP pathway in amelioration of diabetes-associated complications.Environmental science and pollution research international · 2021Review
61 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An important property of NEMO, the core element of the IKK complex involved in NF-kappaB activation, resides in its ability to specifically recognize poly-ubiquitin chains. A small domain called NOA/UBAN has been suggested to be responsible for this property. We recently demonstrated that the C-terminal Zinc Finger (ZF) of NEMO is also able to bind ubiquitin. We show here by ZF swapping and mutagenesis that this represents its only function. While neither NOA nor ZF shows any preference for K63-linked chains, we demonstrate that together they form a bipartite high-affinity K63-specific ubiquitin-binding domain. A similar domain can be found in two other proteins, Optineurin and ABIN2, and can be freely exchanged with that of NEMO without interfering with its activity. This suggests that the main function of the C-terminal half of NEMO is to specifically bind K63-linked poly-ubiquitin chains. We also demonstrate that the recently described binding of NEMO to linear poly-ubiquitin chains is dependent on the NOA alone and does not require the presence of the ZF.
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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.