ArticleProceedings of the National Academy of Sciences of the United States of America2000
A nuclear export signal in the N-terminal regulatory domain of IkappaBalpha controls cytoplasmic localization of inactive NF-kappaB/IkappaBalpha complexes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers.
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Who cites it
153 citing papers in PubMed, 379 citations in OpenAlex.
- Review
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- Synergistic Potential of GLP-1 Receptor Agonists and Radiotherapy in Breast Cancer Treatment: A New Therapeutic Avenue (TROD-GROG 006).Current radiopharmaceuticals · 2025Article
- Mutations of Key Functional Residues in CRM1/XPO1 Differently Alter Its Intranuclear Localization and the Nuclear Export of Endogenous Cargos.Biomolecules · 2024Article
- An insight into the concept of neuroinflammation and neurodegeneration in Alzheimer's disease: targeting molecular approach Nrf2, NF-κB, and CREB.Inflammopharmacology · 2024Review
- Structural and biochemical analyses of the nuclear IκBζ protein in complex with the NF-κB p50 homodimer.Genes & development · 2024Article
- Michael Acceptors as Anti-Cancer Compounds: Coincidence or Causality?International journal of molecular sciences · 2024Review
- Should I stay or should I go? Trafficking of plant extra-nuclear transcription factors.The Plant cell · 2024Review
- Revisiting Neuroblastoma: Nrf2, NF-κB and Phox2B as a Promising Network in Neuroblastoma.Current issues in molecular biology · 2024Review
- Azilsartan Attenuates 3-Nitropropinoic Acid-Induced Neurotoxicity in Rats: The Role of IĸB/NF-ĸB and KEAP1/Nrf2 Signaling Pathways.Neurochemical research · 2024Article
- Characterization of molecular mechanisms driving Merkel cell polyomavirus oncogene transcription and tumorigenic potential.PLoS pathogens · 2023Article
- APEX3 - An Optimized Tool for Rapid and Unbiased Proximity Labeling.Journal of molecular biology · 2023Article
- Lost and Found: The Family of NF-κB Inhibitors Is Larger than Assumed in Salmonid Fish.International journal of molecular sciences · 2023Article
- Overexpression of IκB⍺ modulates NF-κB activation of inflammatory target gene expression.Frontiers in molecular biosciences · 2023Article
- NF-κB in monocytes and macrophages - an inflammatory master regulator in multitalented immune cells.Frontiers in immunology · 2023Review
- Differential recognition of canonical NF-κB dimers by Importin α3.Nature communications · 2022Article
- APAP-Induced IκBβ/NFκB Signaling Drives Hepatic Il6 Expression and Associated Sinusoidal Dilation.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- HAPLN1 confers multiple myeloma cell resistance to several classes of therapeutic drugs.PloS one · 2022Article
93 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Appropriate subcellular localization is crucial for regulation of NF-kappaB function. Herein, we show that latent NF-kappaB complexes can enter and exit the nucleus in preinduction states. The nuclear export inhibitor leptomycin B (LMB) sequestered NF-kappaB/IkappaBalpha complexes in the nucleus. Using deletion and site-directed mutagenesis, we identified a previously uncharacterized nuclear export sequence in residues 45-54 of IkappaBalpha that was required for cytoplasmic localization of inactive complexes. This nuclear export sequence also caused nuclear exclusion of heterologous proteins in a LMB-sensitive manner. Importantly, a LMB-insensitive CRM1 mutant (Crm1-K1) abolished LMB-induced nuclear accumulation of the inactive complexes. Moreover, a cell-permeable p50 NF-kappaB nuclear localization signal peptide also blocked these LMB effects. These results suggest that NF-kappaB/IkappaBalpha complexes shuttle between the cytoplasm and nucleus by a nuclear localization signal-dependent nuclear import and a CRM1-dependent nuclear export. The LMB-induced nuclear complexes could not bind DNA and were inaccessible to signaling events, because LMB inhibited NF-kappaB activation without affecting the subcellular localization of upstream kinases IKKbeta and NIK. Our findings indicate that the dominant nuclear export over nuclear import contributes to the largely cytoplasmic localization of the inactive complexes to achieve efficient NF-kappaB activation by extracellular signals.
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