ArticleNature communications2012
p47 negatively regulates IKK activation by inducing the lysosomal degradation of polyubiquitinated NEMO.
Article in Nature communications, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 59 citations in OpenAlex.
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- Tob negatively regulates NF-κB activation in breast cancer through its association with the TNF receptor complex.Cancer gene therapy · 2025Article
- HCoV-229E Mpro Suppresses RLR-Mediated Innate Immune Signalling Through Cleavage of NEMO and Through Other Mechanisms.International journal of molecular sciences · 2025Article
- Inhibition of cathepsin L ameliorates inflammation through the A20/NF-κB pathway in endotoxin-induced acute lung injury.iScience · 2024Article
- Visualization of the Cdc48 AAA+ ATPase protein unfolding pathway.Nature communications · 2024Article
- p37 regulates VCP/p97 shuttling and functions in the nucleus and cytosol.Science advances · 2024Article
- A fungal core effector exploits the OsPUX8B.2-OsCDC48-6 module to suppress plant immunity.Nature communications · 2024Article
- How autophagy, a potential therapeutic target, regulates intestinal inflammation.Frontiers in immunology · 2023Review
- The Emerging Role of Astrocytic Autophagy in Central Nervous System Disorders.Neurochemical research · 2022Article
- Active conformation of the p97-p47 unfoldase complex.Nature communications · 2022Article
- Valosin Containing Protein (VCP): A Multistep Regulator of Autophagy.International journal of molecular sciences · 2022Review
- Spliceosome-regulated RSRP1-dependent NF-κB activation promotes the glioblastoma mesenchymal phenotype.Neuro-oncology · 2021Article
- Article
- Autophagy in Human T-Cell Leukemia Virus Type 1 (HTLV-1) Induced Leukemia.Frontiers in oncology · 2021Review
- Roles of Specialized Pro-Resolving Lipid Mediators in Autophagy and Inflammation.International journal of molecular sciences · 2020Review
- Degradation of p47 by autophagy contributes to CADM1 overexpression in ATLL cells through the activation of NF-κB.Scientific reports · 2019Article
- Review
- p47 licenses activation of the immune deficiency pathway in the tickProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Gal-3BP Negatively Regulates NF-κB Signaling by Inhibiting the Activation of TAK1.Frontiers in immunology · 2019Article
- HTLV-1-Mediated Epigenetic Pathway to Adult T-Cell Leukemia-Lymphoma.Frontiers in microbiology · 2018Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The persistent or excess activation of NF-κB causes various inflammatory and autoimmune diseases, but the molecular mechanisms that negatively regulate NF-κB activation are not fully understood. Here we show that p47, an essential factor for Golgi membrane fusion, associates with the NEMO subunit of the IκB kinase (IKK) complex upon TNF-α or IL-1 stimulation, and inhibits IKK activation. p47 binds to Lys63-linked and linear polyubiquitin chains, which are conjugated to NEMO upon such stimulation. The binding of p47 to polyubiquitinated NEMO triggers the lysosomal degradation of NEMO, thereby inhibiting IKK activation. The silencing of p47 results in enhanced TNF-α- or IL-1-induced IKK activation, and an increased expression of genes encoding inflammatory mediators. Taken together, our results suggest that p47 is critical for negatively regulating stimulation-induced IKK activation in a manner that is mechanistically distinct from the previously characterized negative regulators, such as A20 and CYLD.
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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.