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.
AuthorsSoon-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
JournalInternational journal of oncology (Int J Oncol) Vol. 40 Issue 5 Pg. 1515-24 (May 2012) ISSN: 1791-2423 [Electronic] Greece
PMID22200884 (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
  • Membrane Proteins
  • Dactinomycin
  • Cytochromes c
  • THEM4 protein, human
  • Thiolester Hydrolases
  • GTP Phosphohydrolases
  • OPA1 protein, human
  • Staurosporine
  • 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)
  • Humans
  • Lung Neoplasms (genetics, metabolism, pathology)
  • Membrane Potential, Mitochondrial
  • Membrane Proteins (genetics, metabolism)
  • Mitochondria (drug effects, metabolism, pathology)
  • RNA Interference
  • Signal Transduction
  • Staurosporine (pharmacology)
  • Thiolester Hydrolases
  • Time Factors
  • Transfection

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