Carboxyl-terminal modulator protein induces apoptosis by regulating mitochondrial function in lung cancer cells.

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.

• Authors: Soon-Kyung Hwang, Arash Minai-Tehrani, Kyeong-Nam Yu, Seung-Hee Chang, Ji-Eun Kim, Kee-Ho Lee, Jongsun Park, George R Beck Jr, Myung-Haing Cho
• Journal: International journal of oncology (Int J Oncol) Vol. 40 Issue 5 Pg. 1515-24 (May 2012) ISSN: 1791-2423 [Electronic] Greece
• PMID: 22200884 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• APAF1 protein, human
• Adaptor Proteins, Signal Transducing
• Apoptotic Protease-Activating Factor 1
• HSP27 Heat-Shock Proteins
• HSPB1 protein, human
• Heat-Shock Proteins
• Membrane Proteins
• Molecular Chaperones
• Dactinomycin
• Cytochromes c
• THEM4 protein, human
• Thiolester Hydrolases
• GTP Phosphohydrolases
• OPA1 protein, human
• Staurosporine

Topics

• Adaptor Proteins, Signal Transducing (genetics, metabolism)
• Apoptosis (drug effects)
• Apoptotic Protease-Activating Factor 1 (metabolism)
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cytochromes c (metabolism)
• Dactinomycin (pharmacology)
• GTP Phosphohydrolases (metabolism)
• HSP27 Heat-Shock Proteins (metabolism)
• Heat-Shock Proteins
• Humans
• Lung Neoplasms (genetics, metabolism, pathology)
• Membrane Potential, Mitochondrial
• Membrane Proteins (genetics, metabolism)
• Mitochondria (drug effects, metabolism, pathology)
• Molecular Chaperones
• RNA Interference
• Signal Transduction
• Staurosporine (pharmacology)
• Thiolester Hydrolases
• Time Factors
• Transfection