ArticleThe Journal of biological chemistry2011
Association of plasminogen activator inhibitor type 2 (PAI-2) with proteasome within endothelial cells activated with inflammatory stimuli.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 32 citations in OpenAlex.
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- Recent Advances in Pathogenesis and Anticoagulation Treatment of Sepsis-Induced Coagulopathy.Journal of inflammation research · 2025Review
- Serum from COVID-19 patients promotes endothelial cell dysfunction through protease-activated receptor 2.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- The Effect of Protease-Activated Receptor-1 (PAR-1) Inhibition on Endothelial-Related Biomarkers in Patients with Coronary Artery Disease.Thrombosis and haemostasis · 2023Article
- All tangled up: interactions of the fibrinolytic and innate immune systems.Frontiers in medicine · 2023Review
- "Super" SERPINs-A stabilizing force against fibrinolysis in thromboinflammatory conditions.Frontiers in cardiovascular medicine · 2023Review
- The Plasminogen-Activator Plasmin System in Physiological and Pathophysiological Angiogenesis.International journal of molecular sciences · 2021Review
- Increased peptidylarginine deiminases expression during the macrophage differentiation and participated inflammatory responses.Arthritis research & therapy · 2019Article
- Identification of downstream target genes regulated by the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate signal pathway in pulmonary hypertension.The Journal of international medical research · 2016Article
- Variant of PAI-2 gene is associated with coronary artery disease and recurrent coronary event risk in Chinese Han population.Lipids in health and disease · 2015Article
- Gene Expression Profiling in Peripheral Blood Cells and Synovial Membranes of Patients with Psoriatic Arthritis.PloS one · 2015Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Quiescent endothelial cells contain low concentrations of plasminogen activator inhibitor type 2 (PAI-2). However, its synthesis can be rapidly stimulated by a variety of inflammatory mediators. In this study, we provide evidence that PAI-2 interacts with proteasome and affects its activity in endothelial cells. To ensure that the PAI-2·proteasome complex is formed in vivo, both proteins were coimmunoprecipitated from endothelial cells and identified with specific antibodies. The specificity of this interaction was evidenced after (a) transfection of HeLa cells with pCMV-PAI-2 and coimmunoprecipitation of both proteins with anti-PAI-2 antibodies and (b) silencing of the PAI-2 gene using specific small interfering RNA (siRNA). Subsequently, cellular distribution of the PAI-2·proteasome complexes was established by immunogold staining and electron microscopy analyses. As judged by confocal microscopy, both proteins appeared in a diffuse cytosolic pattern, but they also could be found in a dense perinuclear and nuclear location. PAI-2 was not polyubiquitinated, suggesting that it bound to proteasome not as the substrate but rather as its inhibitor. Consistently, increased PAI-2 expression (a) abrogated degradation of degron analyzed after cotransfection of HeLa cells with pCMV-PAI-2 and pd2EGFP-N1, (b) prevented degradation of p53, as evidenced both by confocal microscopy and Western immunoblotting, and (c) inhibited proteasome cleavage of specific fluorogenic substrate. This suggests that PAI-2, in endothelial cells induced with inflammatory stimuli, can inhibit proteasome and thus tilt the balance favoring proapoptotic signaling.
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