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BimL displacing Bcl-xL promotes Bax translocation during TNFα-induced apoptosis

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Abstract

Bcl-2 family proteins are implicated as essential regulators in tumor necrosis factor-α (TNFα)-induced apoptosis. BimL, a BH3-only member of Bcl-2 family, can directly or indirectly activate the proapoptotic Bax and the subsequent mitochondrial apoptotic pathway. However, the molecular mechanism of BimL activating Bax activation during TNFα-induced apoptosis is not fully understood. In this study, the role of BimL in Bax activation during TNFα-induced apoptosis was investigated in differentiated PC12 and MCF7 cells, with real-time single-cell analysis. The experimental results show that Bax translocated to mitochondria and cytochrome c (Cyt c) released from mitochondria after TNFα treatment. Furthermore, SP600125 (specific inhibitor of JNK) could inhibit the Cyt c release from mitochondria. Co-immunoprecipitation results show that, the interaction between Bcl-xL and Bax decreased after TNFα treatment, while that between Bcl-xL and BimL increased. Bax did not co-immunoprecipitate with BimL before or after the TNFα treatment. In addition, the increased interaction between BimL and Bcl-xL was dynamically monitored by using fluorescence resonance energy transfer (FRET) technique. Most importantly, there was no evidence of BimL redistribution to mitochondria until cell apoptosis. By comprehensively analyzing these data, it is concluded that BimL displaces Bcl-xL in the mitochondria and promotes Bax translocation during TNFα-induced apoptosis.

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Acknowledgements

This research is supported by the National Natural Science Foundation of China (30600128; 30470494) and the Natural Science Foundation of Guangdong Province (7117865). We thank Dr. A. P. Gilmore (University of Manchester, Oxford Road, UK) for providing the YFP-Bax plasmid and the YFP-Bcl-xL plasmid. We also thank Dr. Y. Gotoh (University of Yokyo, Yayoi, Tokyo, Japan) for providing the DsRed-Mit plasmid.

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  1. MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, South China Normal University, Guangzhou, 510631, China

    Lan Zhang, Da Xing & Miaojuan Chen

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  1. Lan Zhang
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  2. Da Xing
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Correspondence to Da Xing.

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Zhang, L., Xing, D. & Chen, M. BimL displacing Bcl-xL promotes Bax translocation during TNFα-induced apoptosis. Apoptosis 13, 950–958 (2008). https://doi.org/10.1007/s10495-008-0226-5

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