Heat shock protein 70-mediated sensitization of cells to apoptosis by Carboxyl-Terminal Modulator Protein

Longzhen Piao, Yuwen Li, Keum Jin Yang, Kyeong Ah Park, Hee Sun Byun, Minho Won, Janghee Hong, Jeong Lan Kim, Gi Ryang Kweon, Gang Min Hur, Jeong Ho Seok, Jae Youl Cho, Taehoon Chun, Daniel Hess, Ragna Sack, Sauveur Michel Maira, Derek P. Brazil, Brian A. Hemmings, Jongsun Park

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Abstract

Background: The serine/threonine protein kinase B (PKB/Akt) is involved in insulin signaling, cellular survival, and transformation. Carboxyl-terminal modulator protein (CTMP) has been identified as a novel PKB binding partner in a yeast two-hybrid screen, and appears to be a negative PKB regulator with tumor suppressor-like properties. In the present study we investigate novel mechanisms by which CTMP plays a role in apoptosis process. Results: CTMP is localized to mitochondria. Furthermore, CTMP becomes phosphorylated following the treatment of cells with pervanadate, an insulin-mimetic. Two serine residues (Ser37 and Ser38) were identified as novel in vivo phosphorylation sites of CTMP. Association of CTMP and heat shock protein 70 (Hsp70) inhibits the formation of complexes containing apoptotic protease activating factor 1 and Hsp70. Overexpression of CTMP increased the sensitivity of cells to apoptosis, most likely due to the inhibition of Hsp70 function. Conclusion: Our data suggest that phosphorylation on Ser37/Ser38 of CTMP is important for the prevention of mitochondrial localization of CTMP, eventually leading to cell death by binding to Hsp70. In addition to its role in PKB inhibition, CTMP may therefore play a key role in mitochondria-mediated apoptosis by localizing to mitochondria.

Original languageEnglish
Article number53
JournalBMC Cell Biology
Volume10
DOIs
Publication statusPublished - 2009 Jul 15

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ASJC Scopus subject areas

  • Cell Biology

Cite this

Piao, L., Li, Y., Yang, K. J., Park, K. A., Byun, H. S., Won, M., Hong, J., Kim, J. L., Kweon, G. R., Hur, G. M., Seok, J. H., Cho, J. Y., Chun, T., Hess, D., Sack, R., Maira, S. M., Brazil, D. P., Hemmings, B. A., & Park, J. (2009). Heat shock protein 70-mediated sensitization of cells to apoptosis by Carboxyl-Terminal Modulator Protein. BMC Cell Biology, 10, [53]. https://doi.org/10.1186/1471-2121-10-53