ArticleDevelopmental cell2013
Calpain 2 activation of P-TEFb drives megakaryocyte morphogenesis and is disrupted by leukemogenic GATA1 mutation.
Article in Developmental cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- The Kifc3 Motor Protein Controls Centrosomal Factor Cep192 in Ontogenic Coordination of Megakaryocyte Development.bioRxiv : the preprint server for biology · 2026Article
- α-Actinin-1 in Megakaryocytes: Its Structure, Interacting Proteins and Implications for Thrombopoiesis.Biomedicines · 2025Review
- α-Actinin-1 deficiency in megakaryocytes causes low platelet count, platelet dysfunction, and mitochondrial impairment.Blood advances · 2025Article
- Relieving DYRK1A repression of MKL1 confers an adult-like phenotype to human infantile megakaryocytes.The Journal of clinical investigation · 2022Article
- Stepwise GATA1 and SMC3 mutations alter megakaryocyte differentiation in a Down syndrome leukemia model.The Journal of clinical investigation · 2022Article
- Fetal vs adult megakaryopoiesis.Blood · 2022Article
- Epigenetic and Transcriptional Control of Erythropoiesis.Frontiers in genetics · 2022Review
- The Importance of Alpha-Actinin Proteins in Platelet Formation and Function, and Their Causative Role in Congenital Macrothrombocytopenia.International journal of molecular sciences · 2021Review
- CDK9 keeps RNA polymerase II on track.Cellular and molecular life sciences : CMLS · 2021Review
- Review
- Changes in megakaryopoiesis over ontogeny and their implications in health and disease.Platelets · 2020Review
- de novo MEPCE nonsense variant associated with a neurodevelopmental disorder causes disintegration of 7SK snRNP and enhanced RNA polymerase II activation.Scientific reports · 2019Article
- Potent anti-leukemic activity of a specific cyclin-dependent kinase 9 inhibitor in mouse models of chronic lymphocytic leukemia.Oncotarget · 2018Article
- Megakaryocyte ontogeny: Clinical and molecular significance.Experimental hematology · 2018Review
- A specialized pathway for erythroid iron delivery through lysosomal trafficking of transferrin receptor 2.Blood advances · 2017Article
- Neonatal expression of RNA-binding protein IGF2BP3 regulates the human fetal-adult megakaryocyte transition.The Journal of clinical investigation · 2017Article
- Calpain research for drug discovery: challenges and potential.Nature reviews. Drug discovery · 2016Review
- Cracking the control of RNA polymerase II elongation by 7SK snRNP and P-TEFb.Nucleic acids research · 2016Review
- A Child With Dyserythropoietic Anemia and Megakaryocyte Dysplasia Due to a Novel 5'UTR GATA1s Splice Mutation.Pediatric blood & cancer · 2016Article
- Mechanisms and Developmental Roles of Promoter-proximal Pausing of RNA Polymerase II.Journal of stem cell research & therapy · 2016Article
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11 authors at 3 institutions in 2 countries.
Funding
Abstract
Megakaryocyte morphogenesis employs a "hypertrophy-like" developmental program that is dependent on P-TEFb kinase activation and cytoskeletal remodeling. P-TEFb activation classically occurs by a feedback-regulated process of signal-induced, reversible release of active Cdk9-cyclin T modules from large, inactive 7SK small nuclear ribonucleoprotein particle (snRNP) complexes. Here, we have identified an alternative pathway of irreversible P-TEFb activation in megakaryopoiesis that is mediated by dissolution of the 7SK snRNP complex. In this pathway, calpain 2 cleavage of the core 7SK snRNP component MePCE promoted P-TEFb release and consequent upregulation of a cohort of cytoskeleton remodeling factors, including α-actinin-1. In a subset of human megakaryocytic leukemias, the transcription factor GATA1 undergoes truncating mutation (GATA1s). Here, we linked the GATA1s mutation to defects in megakaryocytic upregulation of calpain 2 and of P-TEFb-dependent cytoskeletal remodeling factors. Restoring calpain 2 expression in GATA1s mutant megakaryocytes rescued normal development, implicating this morphogenetic pathway as a target in human leukemogenesis.
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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.