ArticleAmerican journal of physiology. Lung cellular and molecular physiology2016
Hsp90 inhibition suppresses NF-κB transcriptional activation via Sirt-2 in human lung microvascular endothelial cells.
Article in American journal of physiology. Lung cellular and molecular physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- The oncolytic avian reovirus p17 protein triggers chaperone-mediated autophagy by modulating Hsp90 and the T-complex protein-1 ring complex chaperones and co-chaperones to activate the IKK/NF-κB signaling.Journal of virology · 2025Article
- Growth hormone - releasing hormone in the immune system.Reviews in endocrine & metabolic disorders · 2025Review
- Longitudinal proteomic analysis of pathophysiology in plasma and bronchoalveolar lavage fluid of patients with ARDS.Journal of intensive care · 2025Article
- Indole-3-Acetic Acid Protects Against Lipopolysaccharide-induced Endothelial Cell Dysfunction and Lung Injury through the Activation of USP40.American journal of respiratory cell and molecular biology · 2024Article
- Protective role of the HSP90 inhibitor, STA-9090, in lungs of SARS-CoV-2-infected Syrian golden hamsters.BMJ open respiratory research · 2024Article
- Review
- The deubiquitinase USP40 preserves endothelial integrity by targeting the heat shock protein HSP90β.Experimental & molecular medicine · 2024Article
- Matrine regulates Th1/Th2 inflammatory responses by inhibiting the Hsp90/NF-κB signaling axis to alleviate atopic dermatitis.The Kaohsiung journal of medical sciences · 2023Article
- Ganetespib with Methotrexate Acts Synergistically to Impede NF-κB/p65 Signaling in Human Lung Cancer A549 Cells.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Heat shock protein 90 inhibition in the endothelium.Frontiers in medicine · 2023Article
- Proteomics-based investigation of cerebrovascular molecular mechanisms in cerebral amyloid angiopathy by the FFPE-LMD-PCT-SWATH method.Fluids and barriers of the CNS · 2022Article
- Elongation factor-2 kinase is a critical determinant of the fate and antitumor immunity of CD8Science advances · 2022Article
- Multiple Roles of SIRT2 in Regulating Physiological and Pathological Signal Transduction.Genetics research · 2022Review
- Stress-induced inflammation evoked by immunogenic cell death is blunted by the IRE1α kinase inhibitor KIRA6 through HSP60 targeting.Cell death and differentiation · 2022Article
- HSP90 Inhibitors Modulate SARS-CoV-2 Spike Protein Subunit 1-Induced Human Pulmonary Microvascular Endothelial Activation and Barrier Dysfunction.Frontiers in physiology · 2022Article
- Age-Dependent Chronic Lung Injury and Pulmonary Fibrosis following Single Exposure to Hydrochloric Acid.International journal of molecular sciences · 2021Article
- Article
- Elucidation of the Molecular Pathways Involved in the Protective Effects of AUY-922 in LPS-Induced Inflammation in Mouse Lungs.Pharmaceuticals (Basel, Switzerland) · 2021Article
- A screening system for identifying interacting proteins using biomolecular fluorescence complementation and transposon gene trap.PloS one · 2021Article
- P53 deficiency potentiates LPS-Induced acute lung injuryCurrent research in physiology · 2020Article
Corrections and comments
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Authors and funding
8 authors.
Funding
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Abstract
The ability of anti-heat shock protein 90 (Hsp90) drugs to attenuate NF-κB-mediated transcription is the major basis for their anti-inflammatory properties. While the molecular mechanisms underlying this effect are not clear, they appear to be distinct in human endothelial cells. We now show for the first time that type 2 sirtuin (Sirt-2) histone deacetylase binds human NF-κB target gene promoter and prevents the recruitment of NF-κB proteins and subsequent assembly of RNA polymerase II complex in human lung microvascular endothelial cells. Hsp90 inhibitors stabilize the Sirt-2/promoter interaction and impose a "transcriptional block," which is reversed by either inhibition or downregulation of Sirt-2 protein expression. Furthermore, this process is independent of NF-κB (p65) Lysine 310 deacetylation, suggesting that it is distinct from known Sirt-2-dependent mechanisms. We demonstrate that Sirt-2 is recruited to NF-κB target gene promoter via interaction with core histones. Upon inflammatory challenge, chromatin remodeling and core histone H3 displacement from the promoter region removes Sirt-2 and allows NF-κB/coactivator recruitment essential for RNA Pol II-dependent mRNA induction. This novel mechanism may have important implications in pulmonary inflammation.
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