ArticleMolecular cancer2021
The inflammatory kinase IKKα phosphorylates and stabilizes c-Myc and enhances its activity.
Article in Molecular cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 37 citations in OpenAlex.
- The NF-κB Isoform p65 iso5 Is Associated with Distinct Transcriptional Programs and Signaling Pathways.Cells · 2026Article
- c-Myc-PANK3-EMT axis regulates the structure and function of intestinal barrier in ulcerative colitis.Journal of advanced research · 2026Article
- The roles of IKKα in normal physiology and cancer.Cell communication and signaling : CCS · 2026Review
- Spatially-resolved Photoproximity Profiling of MYC Identifies a MYC-BAF Liability in Cancer Cells.bioRxiv : the preprint server for biology · 2025Article
- PAK4 phosphorylates and stabilizes MYC to promote acute myeloid leukemia.Cell insight · 2025Article
- Targeting of IRAK4 and GSPT1 enhances therapeutic efficacy in AML via c-Myc destabilization.Leukemia · 2025Article
- Double trouble: cytosolic and nuclear IKKα in cancer.Open biology · 2025Review
- Plant-derived extracts or compounds for Helicobacter-associated gastritis: a systematic review of their anti-Helicobacter activity and anti-inflammatory effect in animal experiments.Chinese medicine · 2025Review
- Article
- Anti-Cancer Effect of Sulforaphane in Human Pancreatic Cancer Cells Mia PaCa-2.Cancer reports (Hoboken, N.J.) · 2024Article
- Bioinformatic Analysis ofInternational journal of molecular sciences · 2024Article
- NFκB signalling in colorectal cancer: Examining the central dogma of IKKα and IKKβ signalling.Heliyon · 2024Review
- Pharmacological effects and the related mechanism of scutellarin on inflammation-related diseases: a review.Frontiers in pharmacology · 2024Review
- Fire Burn and Cauldron Bubble: What Is in Your Genome Editing Brew?Biochemistry · 2023Review
- Reconstructing the immunosenescence core pathway reveals global characteristics in pan-cancer.Cancer immunology, immunotherapy : CII · 2023Article
- Review
- Calcineurin-mediated dephosphorylation enhances the stability and transactivation of c-Myc.Scientific reports · 2023Article
- Suppression of Inflamm-Aging byMolecules (Basel, Switzerland) · 2023Review
- Targeting Myc-driven stress addiction in colorectal cancer.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2023Review
- Traditional Chinese medicine for transformation of gastric precancerous lesions to gastric cancer: A critical review.World journal of gastrointestinal oncology · 2023Review
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe IκB kinase (IKK) complex, comprising the two enzymes IKKα and IKKβ, is the main activator of the inflammatory transcription factor NF-κB, which is constitutively active in many cancers. While several connections between NF-κB signaling and the oncogene c-Myc have been shown, functional links between the signaling molecules are still poorly studied.
methodsMolecular interactions were shown by co-immunoprecipitation and FRET microscopy. Phosphorylation of c-Myc was shown by kinases assays and its activity by improved reporter gene systems. CRISPR/Cas9-mediated gene knockout and chemical inhibition were used to block IKK activity. The turnover of c-Myc variants was determined by degradation in presence of cycloheximide and by optical pulse-chase experiments.. Immunofluorescence of mouse prostate tissue and bioinformatics of human datasets were applied to correlate IKKα- and c-Myc levels. Cell proliferation was assessed by EdU incorporation and apoptosis by flow cytometry.
resultsWe show that IKKα and IKKβ bind to c-Myc and phosphorylate it at serines 67/71 within a sequence that is highly conserved. Knockout of IKKα decreased c-Myc-activity and increased its T58-phosphorylation, the target site for GSK3β, triggering polyubiquitination and degradation. c-Myc-mutants mimicking IKK-mediated S67/S71-phosphorylation exhibited slower turnover, higher cell proliferation and lower apoptosis, while the opposite was observed for non-phosphorylatable A67/A71-mutants. A significant positive correlation of c-Myc and IKKα levels was noticed in the prostate epithelium of mice and in a variety of human cancers.
conclusionsOur data imply that IKKα phosphorylates c-Myc on serines-67/71, thereby stabilizing it, leading to increased transcriptional activity, higher proliferation and decreased apoptosis.
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