Abstract
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 G2 phases, which corroborates the decreased level of cyclin B1 expression. These observations suggest a new role for BAG3 in regulation of the cell cycle.
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Acknowledgements
We thank past and present members of the Department of Neuroscience and Center for Neurovirology for sharing of ideas and reagents, and their encouragement throughout this study. We also thank Dr Francesca Peruzzi, Dr Davide Eletto and Dr Thersa M Sweet for their advices, William Yen and Jessica Otte for their technical support, Dr Martyn White for his time and assistance in the preparation of the manuscript and C Schriver for editorial assistance. This study is dedicated to our friend and colleague, Dr Arturo Leone. This work was made possible by grants awarded by NIH to KK.
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Gentilella, A., Passiatore, G., Deshmane, S. et al. Activation of BAG3 by Egr-1 in response to FGF-2 in neuroblastoma cells. Oncogene 27, 5011–5018 (2008). https://doi.org/10.1038/onc.2008.142
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DOI: https://doi.org/10.1038/onc.2008.142
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