Carboxyl-terminal modulator protein induces apoptosis by regulating             mitochondrial function in lung cancer cells.
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.
Laboratory of Toxicology, College of Veterinary Medicine Seoul                     National University, Seoul 151-742, Republic of Korea.
Soon-Kyung
SK
Hwang
Arash
A
Minai-Tehrani
Kyeong-Nam
KN
Yu
Seung-Hee
SH
Chang
Ji-Eun
JE
Kim
Kee-Ho
KH
Lee
Jongsun
J
Park
George R
GR
Beck
Myung-Haing
MH
Cho
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D053477:Apoptotic Protease-Activating Factor 1 / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018832:Molecular Chaperones; D034622:RNA Interference; D015398:Signal Transduction; D019311:Staurosporine / Q000494:pharmacology; D013869:Thiolester Hydrolases; D013997:Time Factors; D014162:Transfection
C506592:APAF1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D053477:Apoptotic Protease-Activating Factor 1; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D003609:Dactinomycin; D045304:Cytochromes c; C437985:THEM4 protein, human; D013869:Thiolester Hydrolases; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human; D019311:Staurosporine