Tissue inhibitor of metalloproteinase-1 promotes hematopoietic differentiation via caspase-3 upstream the MEKK1/MEK6/p38alpha pathway
Autor: | C Trentesaux, S Salesse, Laurent Martiny, Elise Lambert, Lucie Bridoux, Emilie Dassé, Emmanuelle Petitfrère, T Baranek, Marie-Line Sowa |
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Rok vydání: | 2007 |
Předmět: |
Cancer Research
medicine.medical_specialty Cysteine Endopeptidases Cellular differentiation p38 mitogen-activated protein kinases MAP Kinase Kinase Kinase 1 Caspase 3 Antigens CD34 MAP Kinase Kinase 6 Biology Cell Line Mitogen-Activated Protein Kinase 14 Antigens CD Internal medicine medicine Humans RNA Small Interfering chemistry.chemical_classification Hematology Tissue Inhibitor of Metalloproteinase-1 Cell Differentiation Tissue inhibitor of metalloproteinase Hematopoietic Stem Cells Cell biology Hematopoiesis Haematopoiesis Enzyme Oncology chemistry |
Zdroj: | Leukemia. 21(4) |
ISSN: | 0887-6924 |
Popis: | Besides its matrix metalloproteinases inhibitory activity, TIMP-1 exhibits other biological activities such as cell survival and proliferation. The intracellular signalling pathway elicited by TIMP-1 begins to be elucidated. We have shown previously that the caspase-3 and the p38alpha MAP kinase were activated during TIMP-1-induced UT-7 cells erythroid differentiation. In this study, we demonstrated that TIMP-1 differentiating effect can be extended to the IL-3-dependent myeloid murine 32D cell line and human erythroid progenitors derived from cord blood CD34(+) cells. By performing small interfering RNA transfection and using chemical inhibitors, we evidenced that caspase-3 was involved in TIMP-1 differentiating effect. We then identified the MEKK1 kinase as a caspase-3 substrate and demonstrated that the MEKK1/MEK6/p38alpha pathway was activated downstream the caspase-3 in TIMP-1-induced hematopoietic differentiation. |
Databáze: | OpenAIRE |
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