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

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

doi:10.1007/s10495-007-0111-7

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

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

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

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.

Original language	English
Pages (from-to)	1893-1900
Number of pages	8
Journal	Apoptosis
Volume	12
Issue number	10
DOIs	https://doi.org/10.1007/s10495-007-0111-7
State	Published - Oct 2007

Keywords

Apoptosis
Bax
MCF-7 cells
PKCε
TNF

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

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.",

keywords = "Apoptosis, Bax, MCF-7 cells, PKCε, TNF",

author = "Dongmei Lu and Usha Sivaprasad and Jie Huang and Eswar Shankar and Shavonda Morrow and Alakananda Basu",

note = "Funding Information: Acknowledgement This work is supported by the grant R01 CA71727 (A. Basu) from the NIH/NCI.",

year = "2007",

month = oct,

doi = "10.1007/s10495-007-0111-7",

language = "English",

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journal = "Apoptosis",

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T1 - Protein kinase C-ε protects MCF-7 cells from TNF-mediated cell death by inhibiting Bax translocation

AU - Lu, Dongmei

AU - Sivaprasad, Usha

AU - Huang, Jie

AU - Shankar, Eswar

AU - Morrow, Shavonda

AU - Basu, Alakananda

N1 - Funding Information: Acknowledgement This work is supported by the grant R01 CA71727 (A. Basu) from the NIH/NCI.

PY - 2007/10

Y1 - 2007/10

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Bax

KW - MCF-7 cells

KW - PKCε

KW - TNF

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U2 - 10.1007/s10495-007-0111-7

DO - 10.1007/s10495-007-0111-7

M3 - Article

C2 - 17668322

AN - SCOPUS:34848886876

SN - 1360-8185

VL - 12

SP - 1893

EP - 1900

JO - Apoptosis

JF - Apoptosis

IS - 10

ER -

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

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