ArticleThe Biochemical journal2022
IKKα plays a major role in canonical NF-κB signalling in colorectal cells.
Article in The Biochemical journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 29 citations in OpenAlex.
- Porcine Reproductive and Respiratory Syndrome Virus NSP8 Suppresses NF-κB Signaling by Hijacking Host UBE2K and IKKα.Viruses · 2026Article
- The roles of IKKα in normal physiology and cancer.Cell communication and signaling : CCS · 2026Review
- NF-κB is a central regulator of hypoxia-induced gene expression.EMBO reports · 2026Article
- CSAD inhibits excessive inflammation during viral infections through the NF-κB signaling pathway.Journal of virology · 2025Article
- Differential RELA and GR recruitment to the BIRC3/BIRC2 locus: Molecular insight as to combinatorial regulation by proinflammatory cytokines and glucocorticoid.Molecular pharmacology · 2025Article
- Double trouble: cytosolic and nuclear IKKα in cancer.Open biology · 2025Review
- Article
- Downregulation of PGAM2 alleviates angiotensin II-induced cardiac hypertrophy by destabilizing HSP90 and inactivating the mTOR/IKKα signaling pathway.International journal of biological sciences · 2025Article
- Article
- Immunomodulatory peptides from sturgeon cartilage: Isolation, identification, molecular docking and effects on RAW264.7 cells.Food chemistry: X · 2024Article
- α7-Nicotinic Acetylcholine Receptor Activation Modulates BV2 Microglial Plasticity via miR-21/TNF-α/NFκB in Oxygen-Glucose Deprivation/Reoxygenation.Journal of molecular neuroscience : MN · 2024Article
- TAK1 expression is associated with increased PD-L1 and decreased cancer-specific survival in microsatellite-stable colorectal cancer.Translational oncology · 2024Article
- NFκB signalling in colorectal cancer: Examining the central dogma of IKKα and IKKβ signalling.Heliyon · 2024Review
- Targeted Treatment against Cancer Stem Cells in Colorectal Cancer.International journal of molecular sciences · 2024Review
- Sustained activation of NF-κB through constitutively active IKKβ leads to senescence bypass in murine dermal fibroblasts.Cell cycle (Georgetown, Tex.) · 2024Article
- The roles and mechanisms of the NF-κB signaling pathway in tendon disorders.Frontiers in veterinary science · 2024Review
- Phosphatase inhibition by sodium orthovanadate displays anti-inflammatory action by suppressing AKT-IKKβ signaling in RAW264.7 cells.Toxicology reports · 2022Article
- The role of constitutive nitric-oxide synthase in regulation of IKKα after ultraviolet irradiation.Photochemistry and photobiologyArticle
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5 authors at 1 institution in 1 country.
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Abstract
Inhibitor of kappa B (IκB) kinase β (IKKβ) has long been viewed as the dominant IKK in the canonical nuclear factor-κB (NF-κB) signalling pathway, with IKKα being more important in non-canonical NF-κB activation. Here we have investigated the role of IKKα and IKKβ in canonical NF-κB activation in colorectal cells using CRISPR-Cas9 knock-out cell lines, siRNA and selective IKKβ inhibitors. IKKα and IKKβ were redundant for IκBα phosphorylation and turnover since loss of IKKα or IKKβ alone had little (SW620 cells) or no (HCT116 cells) effect. However, in HCT116 cells IKKα was the dominant IKK required for basal phosphorylation of p65 at S536, stimulated phosphorylation of p65 at S468, nuclear translocation of p65 and the NF-κB-dependent transcriptional response to both TNFα and IL-1α. In these cells, IKKβ was far less efficient at compensating for the loss of IKKα than IKKα was able to compensate for the loss of IKKβ. This was confirmed when siRNA was used to knock-down the non-targeted kinase in single KO cells. Critically, the selective IKKβ inhibitor BIX02514 confirmed these observations in WT cells and similar results were seen in SW620 cells. Notably, whilst IKKα loss strongly inhibited TNFα-dependent p65 nuclear translocation, IKKα and IKKβ contributed equally to c-Rel nuclear translocation indicating that different NF-κB subunits exhibit different dependencies on these IKKs. These results demonstrate a major role for IKKα in canonical NF-κB signalling in colorectal cells and may be relevant to efforts to design IKK inhibitors, which have focused largely on IKKβ to date.
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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.