ArticleArteriosclerosis, thrombosis, and vascular biology2014
Proteasome proteolysis supports stimulated platelet function and thrombosis.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 53 citations in OpenAlex.
- Mechanisms and consequences of myeloid adhesome dysfunction in atherogenesis.Cardiovascular research · 2025Article
- Unbiased high-throughput screening of drug-repurposing libraries identifies small-molecule inhibitors of clot retraction.Blood advances · 2025Article
- Cardiovascular Toxicity of Proteasome Inhibitors: Underlying Mechanisms and Management Strategies:JACC. CardioOncology · 2023Review
- The platelet transcriptome and proteome in Alzheimer's disease and aging: an exploratory cross-sectional study.Frontiers in molecular biosciences · 2023Article
- Red cell proteasome modulation by storage, redox metabolism and transfusion.Blood transfusion = Trasfusione del sangue · 2022Article
- Sex-specific differences in atherosclerosis, thrombospondin-1, and smooth muscle cell differentiation in metabolic syndrome versus non-metabolic syndrome mice.Frontiers in cardiovascular medicine · 2022Article
- The Role of the Proteasome in Platelet Function.International journal of molecular sciences · 2021Review
- Targeting Thymidine Phosphorylase With Tipiracil Hydrochloride Attenuates Thrombosis Without Increasing Risk of Bleeding in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Platelet Microparticle Controversial Role in Cancer.Advanced pharmaceutical bulletin · 2021Review
- Extracellular Matrix-Specific Platelet Activation Leads to a Differential Translational Response and Protein De Novo Synthesis in Human Platelets.International journal of molecular sciences · 2020Article
- Molecular and functional characteristics of megakaryocytes and platelets in aging.Current opinion in hematology · 2020Review
- Platelets in Healthy and Disease States: From Biomarkers Discovery to Drug Targets Identification by Proteomics.International journal of molecular sciences · 2020Review
- The Integrin Activating Protein Kindlin-3 Is Cleaved in Human Platelets during ST-Elevation Myocardial Infarction.International journal of molecular sciences · 2019Article
- Platelet Proteasome Activity and Metabolism Is Upregulated during Bacterial Sepsis.International journal of molecular sciences · 2019Article
- Human Platelet Protein Ubiquitylation and Changes following GPVI Activation.Thrombosis and haemostasis · 2019Article
- New Insights on Platelets and Platelet-Derived Microparticles in Systemic Lupus Erythematosus.Current rheumatology reports · 2017Review
- Downregulation of Talin-1 expression associates with increased proliferation and migration of vascular smooth muscle cells in aortic dissection.BMC cardiovascular disorders · 2017Article
- Revealing the diversity of extracellular vesicles using high-dimensional flow cytometry analyses.Scientific reports · 2016Article
- Article
- Ferric Chloride-induced Murine Thrombosis Models.Journal of visualized experiments : JoVE · 2016Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
objectiveProteasome inhibitors used in the treatment of hematologic cancers also reduce thrombosis. Whether the proteasome participates in platelet activation or function is unclear because little is known of the proteasome in these terminally differentiated cells. APPROACH AND
resultsPlatelets displayed all 3 primary proteasome protease activities, which MG132 and bortezomib (Velcade) inhibited. Proteasome substrates are marked by ubiquitin, and platelets contained a functional ubiquitination system that modified the proteome by monoubiquitination and polyubiquitination. Systemic MG132 strongly suppressed the formation of occlusive, platelet-rich thrombi in FeCl3-damaged carotid arteries. Transfusion of platelets treated ex vivo with MG132 and washed before transfusion into thrombocytopenic mice also reduced carotid artery thrombosis. Proteasome inhibition reduced platelet aggregation by low thrombin concentrations and ristocetin-stimulated agglutination through the glycoprotein Ib-IX-V complex. This receptor was not appropriately internalized after proteasome inhibition in stimulated platelets, and spreading and clot retraction after MG132 exposure also were decreased. The effects of proteasome inhibitors were not confined to a single receptor as MG132 suppressed thrombin-stimulated, ADP-stimulated, and lipopolysaccharide-stimulated microparticle shedding. Proteasome inhibition increased ubiquitin decoration of cytoplasmic proteins, including the cytoskeletal proteins Filamin A and Talin-1. Mass spectrometry revealed a single MG132-sensitive tryptic cleavage after R1745 in an extended Filamin A loop, which would separate its actin-binding domain from its carboxy terminal glycoprotein Ibα-binding domain.
conclusionsPlatelets contain a ubiquitin/proteasome system that marks cytoskeletal proteins for proteolytic modification to promote productive platelet-platelet and platelet-wall interactions.
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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.