ArticlePharmacological research2015
Erythroid induction of K562 cells treated with mithramycin is associated with inhibition of raptor gene transcription and mammalian target of rapamycin complex 1 (mTORC1) functions.
Article in Pharmacological research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- The Position of Indole Methylation Controls the Structure, DNA Binding, and Cellular Functions of Mithramycin SA-Trp Analogues.Chembiochem : a European journal of chemical biology · 2025Article
- Increased Expression of α-Hemoglobin Stabilizing Protein (AHSP) mRNA in Erythroid Precursor Cells Isolated from β-Thalassemia Patients Treated with Sirolimus (Rapamycin).Journal of clinical medicine · 2024Article
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- Review
- Epigenetic clock and methylation studies in vervet monkeys.GeroScience · 2022Article
- Treatment of Erythroid Precursor Cells from β-Thalassemia Patients withInternational journal of molecular sciences · 2021Article
- DNA methylation age analysis of rapamycin in common marmosets.GeroScience · 2021Article
- A Peptide-Nucleic Acid Targeting miR-335-5p Enhances Expression of Cystic Fibrosis Transmembrane Conductance Regulator (Biomedicines · 2021Article
- Pro-apoptotic activity of novel synthetic isoxazole derivatives exhibiting inhibitory activity against tumor cell growthOncology letters · 2020Article
- The opposing roles of the mTOR signaling pathway in different phases of human umbilical cord blood-derived CD34Stem cells (Dayton, Ohio) · 2020Article
- Efficient Delivery of MicroRNA and AntimiRNA Molecules Using an Argininocalix[4]arene Macrocycle.Molecular therapy. Nucleic acids · 2019Article
- mTOR kinase inhibition reduces tissue factor expression and growth of pancreatic neuroendocrine tumors.Journal of thrombosis and haemostasis : JTH · 2019Article
- BCL11A mRNA Targeting by miR-210: A Possible Network Regulating γ-Globin Gene Expression.International journal of molecular sciences · 2017Article
- An Aγ-globin G->A gene polymorphism associated with βBMC medical genetics · 2017Article
- Structural and Functional Insights on an Uncharacterized Aγ-Globin-Gene Polymorphism Present in Four β0-Thalassemia Families with High Fetal Hemoglobin Levels.Molecular diagnosis & therapy · 2016Article
- Hydroxyurea down-regulates BCL11A, KLF-1 and MYB through miRNA-mediated actions to induce γ-globin expression: implications for new therapeutic approaches of sickle cell disease.Clinical and translational medicine · 2016Article
- Dimerization and DNA recognition rules of mithramycin and its analogues.Journal of inorganic biochemistry · 2016Article
- Development and characterization of K562 cell clones expressing BCL11A-XL: Decreased hemoglobin production with fetal hemoglobin inducers and its rescue with mithramycin.Experimental hematology · 2015Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Rapamycin, an inhibitor of mTOR activity, is a potent inducer of erythroid differentiation and fetal hemoglobin production in β-thalassemic patients. Mithramycin (MTH) was studied to see if this inducer of K562 differentiation also operates through inhibition of mTOR. We can conclude from the study that the mTOR pathway is among the major transcript classes affected by mithramycin-treatment in K562 cells and a sharp decrease of raptor protein production and p70S6 kinase is detectable in mithramycin treated K562 cells. The promoter sequence of the raptor gene contains several Sp1 binding sites which may explain its mechanism of action. We hypothesize that the G+C-selective DNA-binding drug mithramycin is able to interact with these sequences and to inhibit the binding of Sp1 to the raptor promoter due to the following results: (a) MTH strongly inhibits the interactions between Sp1 and Sp1-binding sites of the raptor promoter (studied by electrophoretic mobility shift assays, EMSA); (b) MTH strongly reduces the recruitment of Sp1 transcription factor to the raptor promoter in intact K562 cells (studied by chromatin immunoprecipitation experiments, ChIP); (c) Sp1 decoy oligonucleotides are able to specifically inhibit raptor mRNA accumulation in K562 cells. In conclusion, raptor gene expression is involved in mithramycin-mediated induction of erythroid differentiation of K562 cells and one of its mechanism of action is the inhibition of Sp1 binding to the raptor promoter.
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