ArticleBlood2013
The calcineurin-NFAT pathway negatively regulates megakaryopoiesis.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Calcineurin/NFAT signaling in the temporal integration of Ca²⁺ stress in neurodegeneration.Cell death discovery · 2026Review
- Genome-wide cell type-specific and sex-specific transcriptional dysregulation in the islet of Langerhans underlies islet dysfunction in Down syndrome-related diabetes.bioRxiv : the preprint server for biology · 2026Article
- Calcineurin-NFAT-DSCR1.4 signaling as druggable axis in Gαq-R183Q-driven capillary malformations.Angiogenesis · 2026Article
- Cancer and Post-Therapy Cardiotoxicity Risk in Adolescents, Young Adults, and Adults With Down Syndrome.Comprehensive Physiology · 2025Article
- CRTAC1 enhances the chemosensitivity of non-small cell lung cancer to cisplatin by eliciting RyR-mediated calcium release and inhibiting Akt1 expression.Cell death & disease · 2023Article
- Myeloid Leukemia of Down Syndrome.Cancers · 2023Review
- D-2-Hydroxyglutarate Inhibits Calcineurin Phosphatase Activity to Abolish NF-AT Activation and IL-2 Induction in Stimulated Lymphocytes.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Article
- Deregulated calcium signaling in blood cancer: Underlying mechanisms and therapeutic potential.Frontiers in oncology · 2022Review
- Advances in molecular characterization of myeloid proliferations associated with Down syndrome.Frontiers in genetics · 2022Review
- Review
- Review
- Mechanical Stress Induces CaInternational journal of molecular sciences · 2021Article
- A Short Overview of Changes in Inflammatory Cytokines and Oxidative Stress in Response to Physical Activity and Antioxidant Supplementation.Antioxidants (Basel, Switzerland) · 2020Review
- Gain of chromosome 21 in hematological malignancies: lessons from studying leukemia in children with Down syndrome.Leukemia · 2020Review
- N-Methyl-D-Aspartate Receptor Hypofunction in Meg-01 Cells Reveals a Role for Intracellular Calcium Homeostasis in Balancing Megakaryocytic-Erythroid Differentiation.Thrombosis and haemostasis · 2020Article
- Screening for genes that regulate the differentiation of human megakaryocytic lineage cells.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Inhibition of nuclear factor of activated T cells (NFAT) c3 activation attenuates acute lung injury and pulmonary edema in murine models of sepsis.Oncotarget · 2018Article
- Article
- Phagocytosis-dependent activation of a TLR9-BTK-calcineurin-NFAT pathway co-ordinates innate immunity to Aspergillus fumigatus.EMBO molecular medicine · 2015Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
The calcium regulated calcineurin-nuclear factor of activated T cells (NFAT) pathway modulates the physiology of numerous cell types, including hematopoietic. Upon activation, calcineurin dephosphorylates NFAT family transcription factors, triggering their nuclear entry and activation or repression of target genes. NFATc1 and c2 isoforms are expressed in megakaryocytes. Moreover, human chromosome 21 (Hsa21) encodes several negative regulators of calcineurin-NFAT, candidates in the pathogenesis of Down syndrome (trisomy 21)-associated transient myeloproliferative disorder and acute megakaryoblastic leukemia. To investigate the role of calcineurin-NFAT in megakaryopoiesis, we examined wild-type mice treated with the calcineurin inhibitor cyclosporin A and transgenic mice expressing a targeted single extra copy of Dscr1, an Hsa21-encoded calcineurin inhibitor. Both murine models exhibited thrombocytosis with increased megakaryocytes and megakaryocyte progenitors. Pharmacological or genetic inhibition of calcineurin in mice caused accumulation of megakaryocytes exhibiting enhanced 5-bromo-2'-deoxyuridine uptake and increased expression of messenger RNAs encoding CDK4 and G1 cyclins, which promote cell division. Additionally, human megakaryocytes with trisomy 21 show increased proliferation and decreased NFAT activation compared with euploid controls. Our data indicate that inhibition of calcineurin-NFAT drives proliferation of megakaryocyte precursors by de-repressing genes that drive cell division, providing insights into mechanisms of normal megakaryopoiesis and megakaryocytic abnormalities that accompany Down syndrome.
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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.