ArticleThe EMBO journal2021
Transcriptional repression of NFKBIA triggers constitutive IKK- and proteasome-independent p65/RelA activation in senescence.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 72 citations in OpenAlex.
- Cytokine-induced senescence in tumors is based on sustained activation of STAT1- and NFκB-dependent gene regulatory signatures.GeroScience · 2026Article
- Cellular senescence: six decades of discovery and reinvention.The EMBO journal · 2026Review
- The vicious cycle of SASP and inflammaging promotes aging and age-related diseases.Communications biology · 2026Review
- High-throughput screening identifies FDA approved drug mitiglinide as a novel pyroptosis inhibitor and therapeutic agent for osteoarthritis.Journal of advanced research · 2026Article
- β-cell FMO3-produced TMAO prevents NF-κB-mediated senescence and inflammation in ageing and diabetic conditions.Nature communications · 2026Article
- Epigenetic dynamics of cellular senescence: From mechanistic insights to precision senotherapy.Chinese medical journal · 2026Review
- DNA methylation-mediated memory of obesity in CD4 T lymphocytes perpetuates immune dysregulation.EMBO reports · 2026Article
- PARP1 trapping activates ATM-mediated NF-κB signaling independent of replication in response to TOP1 blockade.Nucleic acids research · 2026Article
- Article
- Senescent Astrocytes: A New Player in Brain Aging and Cognitive Decline.Brain sciences · 2026Review
- Rejuvenating the aging gut by targeting senescence.Nature aging · 2026Article
- Balancing senescence and apoptosis: therapeutic insights into aging and cancer.Molecular and cellular biochemistry · 2025Review
- Article
- Brain Transcriptome Analysis Reveals Exercise Improves Methamphetamine-Induced Impairments in Mouse Learning and Memory Abilities.Addiction biology · 2025Article
- A transcriptome-based human universal senescence index (hUSI) robustly predicts cellular senescence under various conditions.Nature aging · 2025Article
- New Insights into the Role of Cellular Senescence and Its Therapeutic Implications in Ocular Diseases.Bioengineering (Basel, Switzerland) · 2025Review
- Mechanistic Insights into Radiation Resistance in Colorectal Cancer: Gene Exploration Study.International journal of molecular sciences · 2025Article
- AZIN1-dependent polyamine synthesis accelerates tumor cell cycle progression and impairs effector T-cell function in osteosarcoma.Cell death & disease · 2025Article
- Anthocyanins Delay D-Galactose-Induced Mouse Liver Aging by Regulating the NF-κB/IKK Signaling Pathway.Food science & nutrition · 2025Article
- Seneca Valley virus infection exploits DNA damage response to facilitate viral replication.Journal of virology · 2025Article
Corrections and comments
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The IκB kinase (IKK)-NF-κB pathway is activated as part of the DNA damage response and controls both inflammation and resistance to apoptosis. How these distinct functions are achieved remained unknown. We demonstrate here that DNA double-strand breaks elicit two subsequent phases of NF-κB activation in vivo and in vitro, which are mechanistically and functionally distinct. RNA-sequencing reveals that the first-phase controls anti-apoptotic gene expression, while the second drives expression of senescence-associated secretory phenotype (SASP) genes. The rapidly activated first phase is driven by the ATM-PARP1-TRAF6-IKK cascade, which triggers proteasomal destruction of inhibitory IκBα, and is terminated through IκBα re-expression from the NFKBIA gene. The second phase, which is activated days later in senescent cells, is on the other hand independent of IKK and the proteasome. An altered phosphorylation status of NF-κB family member p65/RelA, in part mediated by GSK3β, results in transcriptional silencing of NFKBIA and IKK-independent, constitutive activation of NF-κB in senescence. Collectively, our study reveals a novel physiological mechanism of NF-κB activation with important implications for genotoxic cancer treatment.
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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.