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- W2103532641 abstract "The transcription factor RUNX-1 plays a key role in megakaryocyte differentiation and is mutated in cases of myelodysplastic syndrome and leukemia. In this study, we purified RUNX-1-containing multiprotein complexes from phorbol ester-induced L8057 murine megakaryoblastic cells and identified the ets transcription factor FLI-1 as a novel in vivo-associated factor. The interaction occurs via direct protein-protein interactions and results in synergistic transcriptional activation of the c-mpl promoter. Interestingly, the interaction fails to occur in uninduced cells. Gel filtration chromatography confirms the differentiation-dependent binding and shows that it correlates with the assembly of a complex also containing the key megakaryocyte transcription factors GATA-1 and Friend of GATA-1 (FOG-1). Phosphorylation analysis of FLI-1 with uninduced versus induced L8057 cells suggests the loss of phosphorylation at serine 10 in the induced state. Substitution of Ser10 with the phosphorylation mimic aspartic acid selectively impairs RUNX-1 binding, abrogates transcriptional synergy with RUNX-1, and dominantly inhibits primary fetal liver megakaryocyte differentiation in vitro. Conversely, substitution with alanine, which blocks phosphorylation, augments differentiation of primary megakaryocytes. We propose that dephosphorylation of FLI-1 is a key event in the transcriptional regulation of megakaryocyte maturation. These findings have implications for other cell types where interactions between runx and ets family proteins occur." @default.
- W2103532641 created "2016-06-24" @default.
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- W2103532641 date "2009-08-01" @default.
- W2103532641 modified "2023-10-18" @default.
- W2103532641 title "Differentiation-Dependent Interactions between RUNX-1 and FLI-1 during Megakaryocyte Development" @default.
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- W2103532641 doi "https://doi.org/10.1128/mcb.00090-09" @default.
- W2103532641 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2715817" @default.
- W2103532641 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19470763" @default.
- W2103532641 hasPublicationYear "2009" @default.
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