Tissue inhibitor of metalloproteinase-1 promotes hematopoietic differentiation via caspase-3 upstream the MEKK1/MEK6/p38alpha pathway.
Fiche publication
Date publication
avril 2007
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MARTINY Laurent, Pr DEVARENNE-CHARPENTIER Emmanuelle, Dr SALESSE Stéphanie
Tous les auteurs :
Dasse E, Bridoux L, Baranek T, Lambert E, Salesse S, Sowa ML, Martiny L, Trentesaux C, Petitfrere E
Lien Pubmed
Résumé
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.
Référence
Leukemia. 2007 Apr;21(4):595-603