ArticleJournal of cellular and molecular medicine2010
Crosstalk between the NF-kappaB activating IKK-complex and the CSN signalosome.
Article in Journal of cellular and molecular medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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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
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Prognostic role of c-Jun activation domain-binding protein-1 in cancer: A systematic review and meta-analysis.Journal of cellular and molecular medicine · 2021Pooled it
- Ubiquitination of OsCSN5 by OsPUB45 activates immunity by modulating the OsCUL3a-OsNPR1 module.Science advances · 2025Article
- Linking Environmental Hazards to Osteosarcoma Development: A Comprehensive Review.Cancer management and research · 2025Review
- Regulatory mechanisms and therapeutic potential of JAB1 in neurological development and disorders.Molecular medicine (Cambridge, Mass.) · 2023Review
- Targeting neddylation as a novel approach to lung cancer treatment (Review).International journal of oncology · 2023Review
- NF-κB and AP-1 are required for the lipopolysaccharide-induced expression of MCP-1, CXCL1, and Cx43 in cultured rat dorsal spinal cord astrocytes.Frontiers in molecular neuroscience · 2022Article
- Phosphorylation regulates cullin-based ubiquitination in tumorigenesis.Acta pharmaceutica Sinica. B · 2021Review
- A Different View for an Old Disease: NEDDylation and Other Ubiquitin-Like Post-Translational Modifications in Chronic Lymphocytic Leukemia.Frontiers in oncology · 2021Review
- IKK-Mediated Regulation of the COP9 Signalosome via Phosphorylation of CSN5.Journal of proteome research · 2020Article
- COP9 signalosome complex subunit 5, an IFT20 binding partner, is essential to maintain male germ cell survival and acrosome biogenesis†.Biology of reproduction · 2020Article
- Role of the COP9 Signalosome (CSN) in Cardiovascular Diseases.Biomolecules · 2019Review
- Jab1/COPS5 as a Novel Biomarker for Diagnosis, Prognosis, Therapy Prediction and Therapeutic Tools for Human Cancer.Frontiers in pharmacology · 2018Review
- Knockdown of subunit 3 of the COP9 signalosome inhibits C2C12 myoblast differentiation via NF-KappaB signaling pathway.BMC pharmacology & toxicology · 2017Article
- Role of Myeloma-Derived MIF in Myeloma Cell Adhesion to Bone Marrow and Chemotherapy Response.Journal of the National Cancer Institute · 2016Article
- Integrated molecular analysis of adult T cell leukemia/lymphoma.Nature genetics · 2015Article
- The COP9 signalosome and vascular function: intriguing possibilities?American journal of cardiovascular disease · 2015Review
- Bench-to-bedside review: Immunoglobulin therapy for sepsis - biological plausibility from a critical care perspective.Critical care (London, England) · 2012Review
- An astrocyte-specific proteomic approach to inflammatory responses in experimental rat glaucoma.Investigative ophthalmology & visual science · 2012Article
- JAB1/CSN5: a new player in cell cycle control and cancer.Cell division · 2010Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A great variety of signalling pathways regulating inflammation, cell development and cell survival require NF-kappaB transcription factors, which are normally inactive due to binding to inhibitors, such as IkappaBalpha. The canonical activation pathway of NF-kappaB is initiated by phosphorylation of the inhibitor by an IkappaB kinase (IKK) complex triggering ubiquitination of IkappaB molecules by SCF-type E3-ligase complexes and rapid degradation by 26S-proteasomes. The ubiquitination machinery is regulated by the COP9 signalosome (CSN). We show that IkappaB kinases interact with the CSN-complex, as well as the SCF-ubiquitination machinery, providing an explanation for the rapid signalling-induced ubiquitination and degradation of IkappaBalpha. Furthermore, we reveal that IKK's phosphorylate not only IkappaBalpha, but also the CSN-subunit Csn5/JAB1 (c-Jun activation domain binding protein-1) and that IKK2 influences ubiquitination of Csn5/JAB1. Our observations imply that the CSN complex acts as an inhibitor of constitutive NF-kappaB activity in non-activated cells. Knock-down of Csn5/JAB1 clearly enhanced basal NF-kappaB activity and improved cell survival under stress. The inhibitory effect of Csn5/JAB1 requires a functional MPN(+) metalloprotease domain, which is responsible for cleaving ubiquitin-like Nedd8-modifications. Upon activation of cells with tumour necrosis factor-alpha, the CSN complex dissociates from IKK's allowing full and rapid activation of the NF-kappaB pathway by the concerted action of interacting protein complexes.
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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.