1. Transcriptional upregulation of BAG3 upon proteasome inhibition
- Author
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Wang, Hua-Qin, Liu, Hai-Mei, Zhang, Hai-Yan, Guan, Yifu, and Du, Zhen-Xian
- Subjects
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APOPTOSIS , *PROTEINS , *CANCER cells , *HEAT shock proteins - Abstract
Abstract: Proteasome inhibitors exhibit antitumoral activity against malignancies of different histology. Emerging evidence indicates that antiapoptotic factors may also accumulate as a consequence of exposure to these drugs, thus it seems plausible that activation of survival signaling cascades might compromise their antitumoral effects. Bcl-2-associated athanogene (BAG) family proteins are characterized by their property of interaction with a variety of partners involved in modulating the proliferation/death balance, including heat shock proteins (HSP), Bcl-2, Raf-1. In this report, we demonstrated that BAG3 is a novel antiapoptotic molecule induced by proteasome inhibitors in various cancer cells at the transcriptional level. Moreover, we demonstrated that BAG3 knockdown by siRNA sensitized cancer cells to MG132-induced apoptosis. Taken together, our results suggest that BAG3 induction might represents as an unwanted molecular consequence of utilizing proteasome inhibitors to combat tumors. [Copyright &y& Elsevier]
- Published
- 2008
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