ArticleThe Journal of biological chemistry2008
Tumor suppressor protein p53 regulates megakaryocytic polyploidization and apoptosis.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 45 citations in OpenAlex.
- Unraveling the role ofHemaSphere · 2026Review
- Similar but distinct: The impact of biomechanical forces and culture age on the production, cargo loading, and biological efficacy of human megakaryocytic extracellular vesicles for applications in cell and gene therapies.Bioengineering & translational medicine · 2023Article
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- Targeting the actin/tropomyosin cytoskeleton in epithelial ovarian cancer reveals multiple mechanisms of synergy with anti-microtubule agents.British journal of cancer · 2021Article
- Trp53 regulates platelets in bone marrow via the PI3K pathway.Experimental and therapeutic medicine · 2020Article
- Human megakaryocytic microparticles induce de novo platelet biogenesis in a wild-type murine model.Blood advances · 2020Article
- Induction of differentiation of human stem cellsWorld journal of stem cells · 2019Review
- Prognostic significance of mutated genes in megakaryocytic disorders.Oncology reviews · 2019Article
- Review
- Epigenetic regulation of megakaryocytic and erythroid differentiation by PHF2 histone demethylase.Journal of cellular physiology · 2018Article
- Article
- D-dencichine Regulates Thrombopoiesis by Promoting Megakaryocyte Adhesion, Migration and Proplatelet Formation.Frontiers in pharmacology · 2018Article
- Uncoupling of the Hippo and Rho pathways allows megakaryocytes to escape the tetraploid checkpoint.Haematologica · 2016Article
- Dysregulation of the intrinsic apoptotic pathway mediates megakaryocytic hyperplasia in myeloproliferative neoplasms.Journal of clinical pathology · 2016Article
- Dynamic transcription factor activity profiles reveal key regulatory interactions during megakaryocytic and erythroid differentiation.Biotechnology and bioengineering · 2014Article
- Article
- Nutlin-3 enhances sorafenib efficacy in renal cell carcinoma.Molecular carcinogenesis · 2013Article
- Article
- Proposed megakaryocytic regulon of p53: the genes engaged to control cell cycle and apoptosis during megakaryocytic differentiation.Physiological genomics · 2012Article
- Role of tumor suppressor p53 in megakaryopoiesis and platelet function.Experimental hematology · 2012Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The molecular mechanisms underlying differentiation of hematopoietic stem cells into megakaryocytes are poorly understood. Tumor suppressor protein p53 can act as a transcription factor affecting both cell cycle control and apoptosis, and we have previously shown that p53 is activated during terminal megakaryocytic (Mk) differentiation of the CHRF-288-11 (CHRF) cell line. Here, we use RNA interference to reduce p53 expression in CHRF cells and show that reduced p53 activity leads to a greater fraction of polyploid cells, higher mean and maximum ploidy, accelerated DNA synthesis, and delayed apoptosis and cell death upon phorbol 12-myristate 13-acetate-induced Mk differentiation. In contrast, reduced p53 expression did not affect the ploidy or DNA synthesis of CHRF cells in the absence of phorbol 12-myristate 13-acetate stimulation. Furthermore, primary Mk cells from cultures initiated with p53-null mouse bone marrow mononuclear cells displayed higher ploidy compared with wild-type controls. Quantitative reverse transcription-PCR analysis of p53-knockdown CHRF cells, compared with the "scrambled" control CHRF cells, revealed that six known transcriptional targets of p53 (BBC3, BAX, TP53I3, TP53INP1, MDM2, and P21) were down-regulated, whereas BCL2 expression, which is known to be negatively affected by p53, was up-regulated. These studies show that the functional role of the intrinsic activation of p53 during Mk differentiation is to control polyploidization and the transition to endomitosis by impeding cell cycling and promoting apoptosis.
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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.