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Protein kinase C-ε protects MCF-7 cells from TNF-mediated cell death by inhibiting Bax translocation

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Abstract

We have previously shown that protein kinase Cε (PKCε) acts as an antiapoptotic protein and protects breast cancer MCF-7 cells from tumor necrosis factor-α (TNF)-mediated apoptosis. In the present study, we have investigated the mechanism by which PKCε inhibits TNF-induced cell death. Overexpression of wild-type PKCε (WT-PKCε) in MCF-7 cells decreased TNF-induced mitochondrial depolarization. Depletion of Bax by small interfering RNA (siRNA) attenuated TNF-induced cell death. Overexpression of PKCε in MCF-7 cells decreased dimerization of Bax and its translocation to the mitochondria. Knockdown of PKCε using siRNA induced Bax dimerization and mitochondrial translocation. PKCε was coimmunoprecipitated with Bax in MCF-7 cells. These results suggest that PKCε mediates its antiapoptotic effect partly by preventing activation and translocation of Bax to the mitochondria.

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Acknowledgement

This work is supported by the grant R01 CA71727 (A. Basu) from the NIH/NCI.

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  1. Dongmei Lu

    Present address: Department of Physiology, University of Texas Southwestern Medical Center, 6001 Forest Park RD., Dallas, TX, 75235-9040, USA

Authors and Affiliations

  1. Department of Molecular Biology & Immunology, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX, 76107, USA

    Dongmei Lu, Usha Sivaprasad, Jie Huang, Eswar Shankar, Shavonda Morrow & Alakananda Basu

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  1. Dongmei Lu
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  2. Usha Sivaprasad
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  3. Jie Huang
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  6. Alakananda Basu
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Correspondence to Alakananda Basu.

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Lu, D., Sivaprasad, U., Huang, J. et al. Protein kinase C-ε protects MCF-7 cells from TNF-mediated cell death by inhibiting Bax translocation. Apoptosis 12, 1893–1900 (2007). https://doi.org/10.1007/s10495-007-0111-7

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  • DOI: https://doi.org/10.1007/s10495-007-0111-7

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