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

Piao, Longzhen and Li, Yuwen and Yang, Keum-Jin and Park, Kyeong Ah and Byun, Hee Sun and Won, Minho and Hong, Janghee and Kim, Jeong-Lan and Kweon, Gi Ryang and Hur, Gang Min and Seok, Jeong Ho and Cho, Jae Youl and Chun, Taehoon and Hess, Daniel and Brazil, Derek Patrick and Hemmings, Brian Arthur and Park, Jongsun (2009) Heat shock protein 70-mediated sensitization of cells to apoptosis by Carboxy-Terminal Modulator Protein. BMC Cell Biology, 10 (1). p. 53. ISSN 1471-2121

Abstract

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. CONCLUSIONS: 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.

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Date Deposited: 13 Oct 2015 13:17
Last Modified: 13 Oct 2015 13:17
URI: https://oak.novartis.com/id/eprint/1175

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