Furin gene (fur) regulation in differentiating human megakaryoblastic Dami cells: involvement of the proximal GATA recognition motif in the P1 promoter and impact on the maturation of furin substrates.

摘要: The convertase furin is involved in the maturation of key growth/aggregation mediators synthesized by platelet producers, megakaryocytes, but regulation these cells remains unknown. Computer-assisted search promoter sequence revealed multiple potential binding motifs for GATA-1, suggesting that expressed and regulated cells. Using megakaryoblastic Dami cells, we observed fur mRNA expression increased gradually on phorbol 12-myristate 13-acetate–induced differentiation, reaching maximum levels (8.3-fold increase) at 10 days. Transient transfections with P1, P1A, or P1B fur-LUC–promoter constructs P1 strongest most sensitive to forced GATA-1. Coexpression GATA-1 its comodulator, Friend (FOG-1), resulted a cooperative increase activity. Deletion analysis indicated important GATA-1–regulated sequences are located proximal region promoter. Further 2 GATA-binding positions −66 +62. Point mutation each intactness first GATA site required full basal GATA-1–stimulated Finally, inhibition activity through gene transfer inhibitor α1-AT-PDX led block substrates transforming growth factor-β1 platelet-derived factor. Taken together, results indicate element needed forfur They also suggest proper megakaryocytes has an impact activation megakaryocyte functions.