Notch Signals Inhibit the Development of Erythroid/Megakaryocytic Cells by Suppressing GATA-1 Activity through the Induction of HES1
| Autor: | Jun Ishiko, Yuzuru Kanakura, Masao Mizuki, Itaru Matsumura, Takumi Era, Tariq Enver, Sachiko Ezoe, Yusuke Satoh, Karin Gale, Hirokazu Tanaka, Eri Ishiko, Hirohiko Shibayama |
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| Rok vydání: | 2005 |
| Předmět: |
Erythrocytes
Transcription Genetic HES5 Apoptosis Biochemistry Mice hemic and lymphatic diseases Basic Helix-Loop-Helix Transcription Factors GATA1 Transcription Factor Glycophorins HES1 Luciferases Mice Inbred BALB C Estradiol Receptors Notch Reverse Transcriptase Polymerase Chain Reaction Stem Cells Nuclear Proteins Cell Differentiation Flow Cytometry DNA-Binding Proteins Haematopoiesis Phenotype Proto-Oncogene Proteins c-bcl-2 Receptors Estrogen embryonic structures Erythroid-Specific DNA-Binding Factors Tetradecanoylphorbol Acetate Megakaryocytes Chromatin Immunoprecipitation Immunoblotting bcl-X Protein Biology Transfection Cell Line Granulocyte macrophage colony-stimulating factor receptor Animals Humans Immunoprecipitation Cell Lineage Progenitor cell Molecular Biology Transcription factor Cell Nucleus Homeodomain Proteins Models Genetic Membrane Proteins DNA Cell Biology Blotting Northern Hematopoietic Stem Cells Molecular biology Coculture Techniques Retroviridae Microscopy Fluorescence NIH 3T3 Cells Trans-Activators Transcription Factor HES-1 K562 Cells E1A-Associated p300 Protein Chromatin immunoprecipitation Transcription Factors K562 cells |
| Zdroj: | Journal of Biological Chemistry. 280:4929-4939 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m406788200 |
| Popis: | The effects of Notch signals on the erythroid/megakaryocytic differentiation of hematopoietic cells were examined. Activation of Notch signals by the intracellular Notch1 or an estradiol-inducible form of Notch1/ER suppressed the expression of the erythroid marker glycophorin A in an erythroid/megakaryocytic cell line K562. Although Mock-transfected K562 cells underwent megakaryocytic differentiation in response to 12-O-tetradecanoylphorbol-13-acetate (TPA), estradiol-activated Notch1/ER induced apoptosis during TPA treatment in the transfectant, which was accompanied by the reduced expression of an antiapoptotic molecule Bcl-XL. Even when apoptosis was prevented by the overexpression of Bcl-XL, activated Notch signals still inhibited TPA-induced megakaryocytic differentiation. As for this mechanism, Notch1/recombination signal binding protein J-kappa-induced HES1 but not HES5 was found to inhibit the function of an erythroid/megakaryocytic lineage-specific transcription factor GATA-1. Although HES1 did not affect the DNA binding activity of GATA-1 in gel shift and chromatin immunoprecipitation assays, it directly bound to GATA-1 and dissociated a critical transcriptional cofactor, p300, from GATA-1. Furthermore, overexpressed HES1 inhibited the development of erythroid and megakaryocytic cells in colony assays. Also, the Notch ligand Jagged1 expressed on NIH3T3 cells suppressed the development of erythroid and megakaryocytic cells from cocultured Lin-Sca-1+ hematopoietic stem/progenitor cells. These results suggest that Notch1 inhibits the development of erythroid/megakaryocytic cells by suppressing GATA-1 activity through HES1. |
| Databáze: | OpenAIRE |
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