ArticleCellular and molecular life sciences : CMLS2020
DNA-PK: gatekeeper for IKKγ/NEMO nucleocytoplasmic shuttling in genotoxic stress-induced NF-kappaB activation.
Article in Cellular and molecular life sciences : CMLS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- NEMO/IKKγ: Emerging player in the NF-κB pathway and potential therapeutic target in inflammation.Inflammation · 2026Review
- BNIP3L/BNIP3-Mediated Mitophagy Contributes to the Maintenance of Ovarian Cancer Stem Cells.Journal of cellular and molecular medicine · 2025Article
- Seneca Valley virus infection exploits DNA damage response to facilitate viral replication.Journal of virology · 2025Article
- DNA-PKcs, a player winding and dancing with RNA metabolism and diseases.Cellular & molecular biology letters · 2025Review
- Identifying prioritization of therapeutic targets for ankylosing spondylitis: a multi-omics Mendelian randomization study.Journal of translational medicine · 2024Article
- Huaiyu pill alleviates inflammatory bowel disease in mice blocking toll like receptor 4/ myeloid differentiation primary response gene 88/ nuclear factor kappa B subunit 1 pathway.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2024Article
- ATM-dependent Phosphorylation of Nemo SQ Motifs Is Dispensable for Nemo-mediated Gene Expression Changes in Response to DNA Double-Strand Breaks.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
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- CX3CL1 promotes M1 macrophage polarization and osteoclast differentiation through NF-κB signaling pathway in ankylosing spondylitis in vitro.Journal of translational medicine · 2023Article
- CMTM3 protects the gastric epithelial cells from apoptosis and promotes IL-8 by stabilizing NEMO during Helicobacter pylori infection.Gut pathogens · 2023Article
- DNA-PKcs promotes sepsis-induced multiple organ failure by triggering mitochondrial dysfunction.Journal of advanced research · 2022Article
- Novel mechanisms underlying inhibition of inflammation-induced angiogenesis by dexamethasone and gentamicin via PI3K/AKT/NF-κB/VEGF pathways in acute radiation proctitis.Scientific reports · 2022Article
- Viral Modulation of the DNA Damage Response and Innate Immunity: Two Sides of the Same Coin.Journal of molecular biology · 2022Review
- DNA-PKcs: A Targetable Protumorigenic Protein Kinase.Cancer research · 2022Review
- PARP-1 inhibitors enhance the chemosensitivity of leukemia cells by attenuating NF-кB pathway activity and DNA damage response induced by IdarubicinActa biochimica et biophysica Sinica · 2022Article
- Genome-wide association studies for immunoglobulin concentrations in colostrum and serum in Chinese Holstein.BMC genomics · 2022Article
- GSTpi reduces DNA damage and cell death by regulating the ubiquitination and nuclear translocation of NBS1.Cellular and molecular life sciences : CMLS · 2021Article
- The Use of ProteoTuner Technology to Study Nuclear Factor κB Activation by Heavy Ions.International journal of molecular sciences · 2021Article
- DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy.Signal transduction and targeted therapy · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The transcription factors of the nuclear factor κB (NF-κB) family play a pivotal role in the cellular response to DNA damage. Genotoxic stress-induced activation of NF-κB differs from the classical canonical pathway by shuttling of the NF-κB Essential Modifier (IKKγ/NEMO) subunit through the nucleus. Here, we show that DNA-dependent protein kinase (DNA-PK), an enzyme involved in DNA double-strand break (DSB) repair, triggers the phosphorylation of NEMO by genotoxic stress, thereby enabling shuttling of NEMO through the nucleus with subsequent NF-κB activation. We identified serine 43 of NEMO as a DNA-PK phosphorylation site and point mutation of this serine to alanine led to a complete block of NF-κB activation by ionizing radiation (IR). Blockade of DNA-PK by a specific shRNA or by DNA-PKcs-deficient cells abrogated NEMO entry into the nucleus, as well. Accordingly, SUMOylation of NEMO, a prerequisite of nuclear NEMO, was abolished. Based on these observations, we propose a model in which NEMO phosphorylation by DNA-PK provides the first step in the nucleocytoplasmic trafficking of NEMO.
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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.