ArticleThe Journal of clinical investigation2015
Disturbed flow-activated p90RSK kinase accelerates atherosclerosis by inhibiting SENP2 function.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 91 citations in OpenAlex.
- Senescent Phenotype Induced by p90RSK-NRF2 Signaling Sensitizes Monocytes and Macrophages to Oxidative Stress in HIV-Positive Individuals.Circulation · 2019Trial
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- LATS1/2-CD38 Metabolic Rewiring Links Senescence to Intraplaque Thrombosis.Circulation research · 2026Article
- SUMOylation modulates the dual functions of Krüppel homolog 1 in transcriptional regulation of Broad-Complex expression.Journal of advanced research · 2025Article
- Structural basis for the human SENP5's SUMO isoform discrimination.Nature communications · 2025Article
- Mechanistic insights and emerging therapeutic strategies targeting endothelial dysfunction in cardiovascular diseases.Archives of pharmacal research · 2025Review
- p90RSK modulates inter-and intracellular signaling in kidney diseases.Frontiers in cell and developmental biology · 2025Review
- RSK1 and RSK2 as therapeutic targets: an up-to-date snapshot of emerging data.Expert opinion on therapeutic targets · 2024Review
- Endothelial Reprogramming in Atherosclerosis.Bioengineering (Basel, Switzerland) · 2024Review
- Potential diagnostic markers shared between non-alcoholic fatty liver disease and atherosclerosis determined by machine learning and bioinformatic analysis.Frontiers in medicine · 2024Article
- FAK Family Kinases: A Potential Therapeutic Target for Atherosclerosis.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
- Paradoxes of Cellular SUMOylation Regulation: A Role of Biomolecular Condensates?Pharmacological reviews · 2023Review
- Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies.Signal transduction and targeted therapy · 2023Review
- Article
- The Cajal body marker protein coilin is SUMOylated and possesses SUMO E3 ligase-like activity.Frontiers in RNA research · 2023Article
- Endothelial activation and fibrotic changes are impeded by laminar flow-induced CHK1-SENP2 activity through mechanisms distinct from endothelial-to-mesenchymal cell transition.Frontiers in cardiovascular medicine · 2023Article
- Metabolic regulation of endothelial senescence.Frontiers in cardiovascular medicine · 2023Review
- Possible molecular mechanisms underlying the development of atherosclerosis in cancer survivors.Frontiers in cardiovascular medicine · 2023Review
- 6'-Sialylactose abolished lipopolysaccharide-induced inflammation and hyper-permeability in endothelial cells.Archives of pharmacal research · 2022Article
- SENP2 Promotes VSMC Phenotypic Switching via Myocardin De-SUMOylation.International journal of molecular sciences · 2022Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Disturbed blood flow (d-flow) causes endothelial cell (EC) dysfunction, leading to atherosclerotic plaque formation. We have previously shown that d-flow increases SUMOylation of p53 and ERK5 through downregulation of sentrin/SUMO-specific protease 2 (SENP2) function; however, it is not known how SENP2 itself is regulated by d-flow. Here, we determined that d-flow activated the serine/threonine kinase p90RSK, which subsequently phosphorylated threonine 368 (T368) of SENP2. T368 phosphorylation promoted nuclear export of SENP2, leading to downregulation of eNOS expression and upregulation of proinflammatory adhesion molecule expression and apoptosis. In an LDLR-deficient murine model of atherosclerosis, EC-specific overexpression of p90RSK increased EC dysfunction and lipid accumulation in the aorta compared with control animals; however, these pathologic changes were not observed in atherosclerotic mice overexpressing dominant negative p90RSK (DN-p90RSK). Moreover, depletion of SENP2 in these mice abolished the protective effect of DN-p90RSK overexpression. We propose that p90RSK-mediated SENP2-T368 phosphorylation is a master switch in d-flow-induced signaling, leading to EC dysfunction and atherosclerosis.
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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.