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Tissue inhibitor of metalloproteinase-1 promotes hematopoietic differentiation via caspase-3 upstream the MEKK1/MEK6/p38α pathway

Leukemia volume 21, pages 595–603 (2007)Cite this article

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.

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Acknowledgements

This work was supported by grants from the Ligue Nationale contre le Cancer (Comité de la Haute-Marne).

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Authors and Affiliations

  1. Laboratoire de Biochimie, CNRS 6198, IFR 53 Biomolécules, UFR Sciences Exactes et Naturelles, BP 1039, Université de Reims Champagne Ardenne, Reims, France

    E Dassé, L Bridoux, E Lambert, M L Sowa, L Martiny & E Petitfrère

  2. IPCM 3796, EA, UFR Pharmacie, Reims, France

    T Baranek

  3. Laboratoire de Biologie Cellulaire et Moléculaire, EA 3796, UFR Sciences, Reims, France

    S Salesse

  4. JE 2428, IFR 53 Biomolecules, UFR Pharmacie, Reims, France

    C Trentesaux

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  1. E Dassé
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  2. L Bridoux
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  4. E Lambert
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  9. E Petitfrère
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Correspondence to E Petitfrère.

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Dassé, E., Bridoux, L., Baranek, T. et al. Tissue inhibitor of metalloproteinase-1 promotes hematopoietic differentiation via caspase-3 upstream the MEKK1/MEK6/p38α pathway. Leukemia 21, 595–603 (2007). https://doi.org/10.1038/sj.leu.2404540

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