1. Tissue inhibitor of metalloproteinase-1 promotes hematopoietic differentiation via caspase-3 upstream the MEKK1/MEK6/p38α pathway.
- Author
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Dassé, E., Bridoux, L., Baranek, T., Lambert, E., Salesse, S., Sowa, M. L., Martiny, L., Trentesaux, C., and Petitfrère, E.
- Subjects
METALLOPROTEINASES ,CELL proliferation ,MITOGEN-activated protein kinases ,CELL lines ,CD antigens ,INTERLEUKIN-3 ,CHEMICAL inhibitors - Abstract
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 p38α 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/p38α pathway was activated downstream the caspase-3 in TIMP-1-induced hematopoietic differentiation.Leukemia (2007) 21, 595–603. doi:10.1038/sj.leu.2404540; published online 15 February 2007 [ABSTRACT FROM AUTHOR]- Published
- 2007
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