Activation of BAG3 by Egr-1 in response to FGF-2 in neuroblastoma cells.

The co-chaperone protein, BAG3, which belongs to the BAG protein family, has an established antiapoptotic function in different tumor cell lines. Here we demonstrated that treatment of the human neuroblastoma cell line, SK-N-MC, with fibroblast growth factor-2 (FGF-2) results in induction of BAG3 expression. Induction of BAG3 protein by FGF-2 occurs at the transcriptional level; it requires the extracellular regulated kinase1/2 pathway and is dependent on the activity of Egr-1 upon the BAG3 promoter. Targeted suppression of BAG3 by small-interfering RNA results in dysregulation of cell-cycle progression most notably at S and G(2) phases, which corroborates the decreased level of cyclin B1 expression. These observations suggest a new role for BAG3 in regulation of the cell cycle.