Gentilella A, Passiatore G, Deshmane S, Turco M C, Khalili K
Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, P19122, USA.
Oncogene. 2008 Aug 28;27(37):5011-8. doi: 10.1038/onc.2008.142. Epub 2008 May 12.
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.
共伴侣蛋白BAG3属于BAG蛋白家族，在不同肿瘤细胞系中具有既定的抗凋亡功能。在此我们证明，用成纤维细胞生长因子2（FGF-2）处理人神经母细胞瘤细胞系SK-N-MC会导致BAG3表达的诱导。FGF-2对BAG3蛋白的诱导发生在转录水平；它需要细胞外调节激酶1/2途径，并且依赖于Egr-1对BAG3启动子的活性。用小干扰RNA靶向抑制BAG3会导致细胞周期进程失调，最明显的是在S期和G2期，这证实了细胞周期蛋白B1表达水平的降低。这些观察结果表明BAG3在细胞周期调节中具有新的作用。
