ArticleThe Journal of biological chemistry2009
NEMO-binding domains of both IKKalpha and IKKbeta regulate IkappaB kinase complex assembly and classical NF-kappaB activation.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Defective Function of Inhibitor of κB Kinase Subunit Beta Associated With Multiple Immune-Mediated Disorders.Experimental dermatology · 2026Article
- Proteomic analysis of dental pulp from deciduous teeth in comparison to permanent teeth: an in-vitro study.European archives of paediatric dentistry : official journal of the European Academy of Paediatric Dentistry · 2025Article
- Genetic and Functional Dissection of the NFKB2 Gene: Implications for Milk Fatty Acid Biosynthesis in Dairy Cattle.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Integrative Multi-PTM Proteomics Reveals Dynamic Global, Redox, Phosphorylation, and Acetylation Regulation in Cytokine-Treated Pancreatic Beta Cells.Molecular & cellular proteomics : MCP · 2024Article
- IKKα plays a major role in canonical NF-κB signalling in colorectal cells.The Biochemical journal · 2022Article
- Pparg signaling controls bladder cancer subtype and immune exclusion.Nature communications · 2021Article
- Multifunctional Peptides from Spanish Dry-Cured Pork Ham: Endothelial Responses and Molecular Modeling Studies.International journal of molecular sciences · 2019Article
- Targeting of NF-κB to Dendritic Spines Is Required for Synaptic Signaling and Spine Development.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Classical NF-κB Metabolically Reprograms Sarcoma Cells Through Regulation of Hexokinase 2.Frontiers in oncology · 2018Article
- Isoliquiritigenin attenuates LPS-induced AKI by suppression of inflammation involving NF-κB pathway.American journal of translational research · 2018Article
- Structural Basis for the Activation of IKK1/α.Cell reports · 2016Article
- Polyubiquitin Drives the Molecular Interactions of the NF-κB Essential Modulator (NEMO) by Allosteric Regulation.The Journal of biological chemistry · 2015Article
- Protein engineering of the N-terminus of NEMO: structure stabilization and rescue of IKKβ binding.Biochemistry · 2014Article
- Noncanonical NF-κB signaling is limited by classical NF-κB activity.Science signaling · 2014Article
- Article
- Genome wide association study identifies 20 novel promising genes associated with milk fatty acid traits in Chinese Holstein.PloS one · 2014Article
- Cardiomyocyte-specific p65 NF-κB deletion protects the injured heart by preservation of calcium handling.American journal of physiology. Heart and circulatory physiology · 2013Article
- The MC159 protein from the molluscum contagiosum poxvirus inhibits NF-κB activation by interacting with the IκB kinase complex.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- Tumor necrosis factor α-mediated induction of interleukin 17C in human keratinocytes is controlled by nuclear factor κB.The Journal of biological chemistry · 2011Article
- NEMO-binding domain peptide inhibits constitutive NF-κB activity and reduces tumor burden in a canine model of relapsed, refractory diffuse large B-cell lymphoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2011Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Proinflammatory NF-kappaB activation requires the IkappaB (inhibitor of NF-kappaB) kinase (IKK) complex that contains two catalytic subunits named IKKalpha and IKKbeta and a regulatory subunit named NF-kappaB essential modulator (NEMO). NEMO and IKKbeta are essential for tumor necrosis factor (TNF)-induced NF-kappaB activation, and we recently demonstrated that NEMO and IKKalpha are sufficient for interleukin (IL)-1-induced signaling. IKKalpha and IKKbeta both contain a functional NEMO-binding domain (NBD); however, the role of NEMO association with each kinase in NF-kappaB signaling and IKK complex formation remains unclear. To address this question, we stably reconstituted IKKalpha(-/-) and IKKbeta(-/-) murine embryonic fibroblasts (MEFs) with wild-type (WT) or NBD-deficient (DeltaNBD) versions of IKKalpha and IKKbeta, respectively. TNF-induced classical NF-kappaB activation in IKKbeta(-/-) MEFs was rescued by IKKbeta(WT) but not IKKbeta(DeltaNBD), whereas neither IKKbeta(WT) nor IKKbeta(DeltaNBD) affected IL-1-induced NF-kappaB signaling. As previously described, classical NF-kappaB transcriptional activity was absent in IKKalpha(-/-) cells. Reconstitution with either IKKalpha(WT) or IKKalpha(DeltaNBD) rescued both IL-1 and TNF-induced transcription, demonstrating that NEMO association is not required for IKKalpha-dependent regulation of NF-kappaB-dependent transcription. Stably expressed IKKalpha(WT) or IKKbeta(WT) associated with endogenous IKKs and NEMO in IKKalpha(-/-) or IKKbeta(-/-) MEFs, respectively, resulting in formation of the heterotrimeric IKKalpha-IKKbeta-NEMO complex. In contrast, although the IKKalpha(DeltaNBD) and IKKbeta(DeltaNBD) mutants associated with endogenous IKKs containing an NBD, these dimeric endogenous IKK-IKK(DeltaNBD) complexes did not associate with NEMO. These findings therefore demonstrate that formation of the heterotrimeric IKKalpha-IKKbeta-NEMO holocomplex absolutely requires two intact NEMO-binding domains.
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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.