Abstract
Serine/threonine protein kinase B (PKB/Akt) is involved in cell survival and growth. Carboxyl-terminal modulator protein (CTMP), a novel Akt binding partner, prevents Akt activation at the plasma membrane in response to various stimuli, and thus possesses a tumor suppressor-like function. In a previous study, we have demonstrated that CTMP inhibits tumor progression by facilitating apoptosis in a mouse lung cancer model. However, the precise mechanism of CTMP-induced apoptosis remains to be elucidated. The present study was performed to examine the role of CTMP in mitochondrial-mediated apoptosis and regulation of mitochondrial function in human lung carcinoma cells. Our results showed that CTMP altered mitochondrial morphology and caused the release of cytochrome c by inhibiting OPA1 expression. Additionally, CTMP facilitated mitochondrial-mediated apoptosis by inhibiting heat-shock protein 27 and preventing cytochrome c interaction with Apaf-1. Our data suggest that CTMP may therefore play a critical role in mitochondrial-mediated apoptosis in lung cancer cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Apoptosis* / drug effects
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Apoptotic Protease-Activating Factor 1 / metabolism
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Carcinoma, Non-Small-Cell Lung / genetics
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Carcinoma, Non-Small-Cell Lung / metabolism*
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Carcinoma, Non-Small-Cell Lung / pathology
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Cell Line, Tumor
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Cytochromes c / metabolism
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Dactinomycin / pharmacology
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GTP Phosphohydrolases / metabolism
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HSP27 Heat-Shock Proteins / metabolism
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Heat-Shock Proteins
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Humans
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Lung Neoplasms / genetics
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Lung Neoplasms / metabolism*
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Lung Neoplasms / pathology
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Membrane Potential, Mitochondrial
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mitochondria / drug effects
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Mitochondria / metabolism*
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Mitochondria / pathology
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Molecular Chaperones
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RNA Interference
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Signal Transduction
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Staurosporine / pharmacology
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Thiolester Hydrolases
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Time Factors
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Transfection
Substances
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APAF1 protein, human
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Adaptor Proteins, Signal Transducing
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Apoptotic Protease-Activating Factor 1
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HSP27 Heat-Shock Proteins
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HSPB1 protein, human
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Heat-Shock Proteins
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Membrane Proteins
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Molecular Chaperones
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Dactinomycin
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Cytochromes c
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THEM4 protein, human
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Thiolester Hydrolases
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GTP Phosphohydrolases
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OPA1 protein, human
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Staurosporine