ArticleThe Journal of clinical investigation2014
Proteasome function is required for platelet production.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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
32 citing papers in PubMed, 73 citations in OpenAlex.
- Phase II trial of R-CHOP plus bortezomib induction therapy followed by bortezomib maintenance for newly diagnosed mantle cell lymphoma: SWOG S0601.British journal of haematology · 2016Trial
- ER-associated degradation pathway protein SEL1L plays an evolutionarily conserved role in platelet adhesion.The Journal of clinical investigation · 2026Article
- Bortezomib induces Rho-dependent hyperpermeability of endothelial cells synergistically with inflammatory mediators.BMC pulmonary medicine · 2024Article
- Romiplostim in chemotherapy-induced thrombocytopenia: A review of the literature.Cancer medicine · 2024Review
- Cell cycle-dependent centrosome clustering precedes proplatelet formation.Science advances · 2024Article
- The predominant PAR4 variant in individuals of African ancestry worsens murine and human stroke outcomes.The Journal of clinical investigation · 2023Article
- Bone-Targeted Bortezomib Inhibits Bortezomib-Resistant Multiple Myeloma in Mice by Providing Higher Levels of Bortezomib in Bone.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Downregulation of ADAM17 in pediatric immune thrombocytopenia impairs proplatelet formation.BMC pediatrics · 2022Article
- Platelet-Released Factors: Their Role in Viral Disease and Applications for Extracellular Vesicle (EV) Therapy.International journal of molecular sciences · 2022Review
- Overexpressed Smurf1 is degraded in glioblastoma cells through autophagy in a p62-dependent manner.FEBS open bio · 2022Article
- Megakaryocyte-specific knockout of the Mir-99b/let7e/125a cluster lowers platelet count without altering platelet function.Blood cells, molecules & diseases · 2021Article
- The Proteasome Inhibitor Bortezomib Induces Apoptosis and Activation in Gel-Filtered Human Platelets.International journal of molecular sciences · 2021Article
- Bisphosphonates for delivering drugs to bone.British journal of pharmacology · 2021Review
- The Role of the Proteasome in Platelet Function.International journal of molecular sciences · 2021Review
- Challenges and Advances in Managing Thrombocytopenic Cancer Patients.Journal of clinical medicine · 2021Review
- Targeting Bortezomib to Bone Increases Its Bone Anabolic Activity and Reduces Systemic Adverse Effects in Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2020Article
- Glucose Metabolism Is Required for Platelet Hyperactivation in a Murine Model of Type 1 Diabetes.Diabetes · 2019Article
- Platelet biology and functions: new concepts and clinical perspectives.Nature reviews. Cardiology · 2019Review
- Glucose Transporter 3 Potentiates Degranulation and Is Required for Platelet Activation.Arteriosclerosis, thrombosis, and vascular biology · 2017Article
- Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
Abstract
The proteasome inhibiter bortezomib has been successfully used to treat patients with relapsed multiple myeloma; however, many of these patients become thrombocytopenic, and it is not clear how the proteasome influences platelet production. Here we determined that pharmacologic inhibition of proteasome activity blocks proplatelet formation in human and mouse megakaryocytes. We also found that megakaryocytes isolated from mice deficient for PSMC1, an essential subunit of the 26S proteasome, fail to produce proplatelets. Consistent with decreased proplatelet formation, mice lacking PSMC1 in platelets (Psmc1(fl/fl) Pf4-Cre mice) exhibited severe thrombocytopenia and died shortly after birth. The failure to produce proplatelets in proteasome-inhibited megakaryocytes was due to upregulation and hyperactivation of the small GTPase, RhoA, rather than NF-κB, as has been previously suggested. Inhibition of RhoA or its downstream target, Rho-associated protein kinase (ROCK), restored megakaryocyte proplatelet formation in the setting of proteasome inhibition in vitro. Similarly, fasudil, a ROCK inhibitor used clinically to treat cerebral vasospasm, restored platelet counts in adult mice that were made thrombocytopenic by tamoxifen-induced suppression of proteasome activity in megakaryocytes and platelets (Psmc1(fl/fl) Pdgf-Cre-ER mice). These results indicate that proteasome function is critical for thrombopoiesis, and suggest inhibition of RhoA signaling as a potential strategy to treat thrombocytopenia in bortezomib-treated multiple myeloma patients.
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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.