ArticleJournal of the American Heart Association2013
Targeting nuclear import shuttles, importins/karyopherins alpha by a peptide mimicking the NFκB1/p50 nuclear localization sequence.
Article in Journal of the American Heart Association, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
- Therapeutic Approaches Interfering with Nuclear Localization Signals: An Emerging Strategy for CNS-Related Diseases.Current neuropharmacology · 2026Review
- Review
- PCV2 Cap protein nuclear import via importin α/β receptor: molecular insights and antiviral potential.Frontiers in microbiology · 2025Article
- The peptide genomic therapy increases antibacterial immunity and survival in sepsis by reprograming the gene orthologs of human immunodeficiencies in the spleen and lungs.Frontiers in immunology · 2025Article
- Di-caffeoylquinic acid: a potential inhibitor for amyloid-beta aggregation.Journal of natural medicines · 2024Article
- Beyond Transduction: Anti-Inflammatory Effects of Cell Penetrating Peptides.Molecules (Basel, Switzerland) · 2024Review
- Anti-inflammatory control of human skin keratinocytes by targeting nuclear transport checkpoint.Skin health and disease · 2024Article
- Advances and transgressions of nuclear transport checkpoint inhibitors.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Intracellular delivery of nuclear localization sequence peptide mitigates COVID-19 by inhibiting nuclear transport of inflammation-associated transcription factors.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Data-driven discovery of innate immunomodulatorsChemical science · 2023Article
- Activation of thousands of genes in the lungs and kidneys by sepsis is countered by the selective nuclear blockade.Frontiers in immunology · 2023Article
- Genomic control of inflammation in experimental atopic dermatitis.Scientific reports · 2022Article
- Review
- Hyperlipidemic hypersensitivity to lethal microbial inflammation and its reversal by selective targeting of nuclear transport shuttles.Scientific reports · 2021Article
- Increased vaccine tolerability and protection via NF-κB modulation.Science advances · 2020Article
- Early Initiation of Sacubitril/Valsartan in Patients with Chronic Heart Failure After Acute Decompensation: A Case Series Analysis.Clinical drug investigation · 2020Article
- Decoding inflammation, its causes, genomic responses, and emerging countermeasures.Scandinavian journal of immunology · 2019Review
- Protection from Endotoxin Shock by Selective Targeting of Proinflammatory Signaling to the Nucleus Mediated by Importin Alpha 5.ImmunoHorizons · 2019Article
- Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions.Beilstein journal of organic chemistry · 2018Article
- DNA polymerase β contains a functional nuclear localization signal at its N-terminus.Nucleic acids research · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundWe recently reported that a bifunctional nuclear transport modifier (NTM), cSN50.1 peptide, reduced atherosclerosis, plasma cholesterol, triglycerides, and glucose along with liver fat and inflammatory markers, in a murine model of familial hypercholesterolemia. We determined that cSN50.1 improved lipid homeostasis by modulating nuclear transport of sterol regulatory element-binding proteins through interaction with importin β. Previous studies established that cSN50.1 and related NTMs also modulate nuclear transport of proinflammatory transcription factors mediated by binding of their nuclear localization sequences (NLSs) to importins/karyopherins α. However, selectivity and specificity of NTMs for importins/karyopherins α were undetermined. METHODS AND
resultsWe analyzed interaction of the NTM hydrophilic module, N50 peptide, derived from the NLS of NFκB1/p50, with endogenous human importins/karyopherins α to determine the mechanism of NTM modulation of importin α-mediated nuclear transport. We show that N50 peptide forms stable complexes with multiple importins/karyopherins α. However, only interaction with importin α5 (Imp α5) displayed specific, high-affinity binding. The 2:1 stoichiometry of the N50-Imp α5 interaction (KD1 = 73 nmol/L, KD2 = 140 nmol/L) indicated occupancy of both major and minor NLS binding pockets. Utilizing in silico 3-dimensional (3-D) docking models and comparative structural analysis, we identified a structural component of the Imp α5 major NLS binding pocket that may stabilize N50 binding. Imp α5 also displayed rapid stimulus-induced turnover, which could influence its availability for nuclear transport during the inflammatory response.
conclusionsThese results provide direct evidence that N50 peptide selectively targets Imp α5, encouraging further refinement of NLS-derived peptides as new tools to modulate inflammatory disorders.
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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.