ArticleThe Journal of biological chemistry2015
Polyubiquitin Drives the Molecular Interactions of the NF-κB Essential Modulator (NEMO) by Allosteric Regulation.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed.
- Unanchored ubiquitin chains promote the non-canonical inflammasome via UBXN1.Research square · 2026Article
- Ubiquitination and autophagy in host-pathogen interactions: from immune surveillance to therapeutic targeting.Nature reviews. Immunology · 2026Review
- NEMO/IKKγ: Emerging player in the NF-κB pathway and potential therapeutic target in inflammation.Inflammation · 2026Review
- Review
- Molecular mechanism of IKK catalytic dimer docking to NF-κB substrates.Nature communications · 2024Article
- DCAF7 Acts as A Scaffold to Recruit USP10 for G3BP1 Deubiquitylation and Facilitates Chemoresistance and Metastasis in Nasopharyngeal Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- A conserved core region of the scaffold NEMO is essential for signal-induced conformational change and liquid-liquid phase separation.The Journal of biological chemistry · 2023Article
- A Conserved Core Region of the Scaffold NEMO is Essential for Signal-induced Conformational Change and Liquid-liquid Phase Separation.bioRxiv : the preprint server for biology · 2023Article
- Linear ubiquitination induces NEMO phase separation to activate NF-κB signaling.Life science alliance · 2023Article
- Molluscum Contagiosum Virus Protein MC008 Targets NF-κB Activation by Inhibiting Ubiquitination of NEMO.Journal of virology · 2023Article
- Mechanistic insights into the activation of the IKK kinase complex by the Kaposi's sarcoma herpes virus oncoprotein vFLIP.The Journal of biological chemistry · 2022Article
- Epsins 1 and 2 promote NEMO linear ubiquitination via LUBAC to drive breast cancer development.The Journal of clinical investigation · 2021Article
- A Thermodynamic Model for Interpreting Tryptophan Excitation-Energy-Dependent Fluorescence Spectra Provides Insight Into Protein Conformational Sampling and Stability.Frontiers in molecular biosciences · 2021Article
- The dynamics of linear polyubiquitin.Science advances · 2020Article
- Article
- Unanchored Ubiquitin Chains, Revisited.Frontiers in cell and developmental biology · 2020Review
- A Central Region of NF-κB Essential Modulator Is Required for IKKβ-Induced Conformational Change and for Signal Propagation.Biochemistry · 2019Article
- Evidence for M1-Linked Polyubiquitin-Mediated Conformational Change in NEMO.Journal of molecular biology · 2017Article
- Characterization of the first naturally thermostable terpene synthases and development of strategies to improve thermostability in this family of enzymes.The FEBS journal · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The NF-κB essential modulator (NEMO) is the master regulator of NF-κB signaling, controlling the immune and nervous systems. NEMO affects the activity of IκB kinase-β (IKKβ), which relieves the inhibition of the NF-κB transcriptional regulation machinery. Despite major effort, there is only a very sparse, phenomenological understanding of how NEMO regulates IKKβ and shows specificity in its large range of molecular interactions. We explore the key molecular interactions of NEMO using a molecular biophysics approach, incorporating rapid-mixing stopped-flow, high-pressure, and CD spectroscopies. Our study demonstrates that NEMO has a significant degree of native structural disorder and that molecular flexibility and ligand-induced conformational change are at the heart of the molecular interactions of NEMO. We found that long chain length, unanchored, linear polyubiquitin drives NEMO activity, enhancing the affinity of NEMO for IKKβ and the kinase substrate IκBα and promoting membrane association. We present evidence that unanchored polyubiquitin achieves this regulation by inducing NEMO conformational change by an allosteric mechanism. We combine our quantitative findings to give a detailed molecular mechanistic model for the activity of NEMO, providing insight into the molecular mechanism of NEMO activity with broad implications for the biological role of free polyubiquitin.
Indexed as
Identifiers
What OpenQuestion holds
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.