ArticleScientific reports2016
Inhibition of Canonical NF-κB Signaling by a Small Molecule Targeting NEMO-Ubiquitin Interaction.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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
19 citing papers in PubMed, 31 citations in OpenAlex.
- NEMO/IKKγ: Emerging player in the NF-κB pathway and potential therapeutic target in inflammation.Inflammation · 2026Review
- Review
- Secondary interactions in ubiquitin-binding domains achieve linkage or substrate specificity.Cell reports · 2024Article
- The therapeutic potential of targeting regulated non-apoptotic cell death.Nature reviews. Drug discovery · 2023Review
- Linear ubiquitination induces NEMO phase separation to activate NF-κB signaling.Life science alliance · 2023Article
- Advances in targeting 'undruggable' transcription factors with small molecules.Nature reviews. Drug discovery · 2021Review
- The dynamics of linear polyubiquitin.Science advances · 2020Article
- Transcription Factor Inhibition: Lessons Learned and Emerging Targets.Trends in molecular medicine · 2020Review
- Determination of Protein Structural Ensembles by Hybrid-Resolution SAXS Restrained Molecular Dynamics.Journal of chemical theory and computation · 2020Article
- Antagonizing binding of cell cycle and apoptosis regulatory protein 1 (CARP-1) to the NEMO/IKKγ protein enhances the anticancer effect of chemotherapy.The Journal of biological chemistry · 2020Article
- Oxygen-dependent asparagine hydroxylation of the ubiquitin-associated (UBA) domain in Cezanne regulates ubiquitin binding.The Journal of biological chemistry · 2020Article
- Rubicon: a facilitator of viral immune evasion.Cellular & molecular immunology · 2019Article
- Multifunctional Peptides from Spanish Dry-Cured Pork Ham: Endothelial Responses and Molecular Modeling Studies.International journal of molecular sciences · 2019Article
- FAM105A/OTULINL Is a Pseudodeubiquitinase of the OTU-Class that Localizes to the ER Membrane.Structure (London, England : 1993) · 2019Article
- Targeting TRAF6 E3 ligase activity with a small-molecule inhibitor combats autoimmunity.The Journal of biological chemistry · 2018Article
- Targeting IKKβ in Cancer: Challenges and Opportunities for the Therapeutic Utilisation of IKKβ Inhibitors.Cells · 2018Review
- Structures of REV1 UBM2 Domain Complex with Ubiquitin and with a Small-Molecule that Inhibits the REV1 UBM2-Ubiquitin Interaction.Journal of molecular biology · 2018Article
- Inhibitors of protein-protein interactions (PPIs): an analysis of scaffold choices and buried surface area.Current opinion in chemical biology · 2018Review
- Unlocking the NF-κB Conundrum: Embracing Complexity to Achieve Specificity.Biomedicines · 2017Review
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The IκB kinase (IKK) complex acts as the gatekeeper of canonical NF-κB signaling, thereby regulating immunity, inflammation and cancer. It consists of the catalytic subunits IKKα and IKKβ and the regulatory subunit NEMO/IKKγ. Here, we show that the ubiquitin binding domain (UBAN) in NEMO is essential for IKK/NF-κB activation in response to TNFα, but not IL-1β stimulation. By screening a natural compound library we identified an anthraquinone derivative that acts as an inhibitor of NEMO-ubiquitin binding (iNUB). Using biochemical and NMR experiments we demonstrate that iNUB binds to NEMOUBAN and competes for interaction with methionine-1-linked linear ubiquitin chains. iNUB inhibited NF-κB activation upon UBAN-dependent TNFα and TCR/CD28, but not UBAN-independent IL-1β stimulation. Moreover, iNUB was selectively killing lymphoma cells that are addicted to chronic B-cell receptor triggered IKK/NF-κB activation. Thus, iNUB disrupts the NEMO-ubiquitin protein-protein interaction interface and thereby inhibits physiological and pathological NF-κB signaling.
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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.