title: Heat shock protein 70-mediated sensitization of cells to apoptosis by Carboxyl-Terminal Modulator Protein.
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.
authors: Department of Pharmacology, Daejeon Regional Cancer Center, Cancer Research Institute, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Taejeon, 301-131, Korea. plz1978@hanmail.net
authors: Longzhen
authors: L
authors: Piao
authors: Yuwen
authors: Y
authors: Li
authors: Keum-Jin
authors: KJ
authors: Yang
authors: Kyeong Ah
authors: KA
authors: Park
authors: Hee Sun
authors: HS
authors: Byun
authors: Minho
authors: M
authors: Won
authors: Janghee
authors: J
authors: Hong
authors: Jeong-Lan
authors: JL
authors: Kim
authors: Gi Ryang
authors: GR
authors: Kweon
authors: Gang Min
authors: GM
authors: Hur
authors: Jeong Ho
authors: JH
authors: Seok
authors: Jae Youl
authors: JY
authors: Cho
authors: Taehoon
authors: T
authors: Chun
authors: Daniel
authors: D
authors: Hess
authors: Ragna
authors: R
authors: Sack
authors: Sauveur-Michel
authors: SM
authors: Maira
authors: Derek P
authors: DP
authors: Brazil
authors: Brian A
authors: BA
authors: Hemmings
authors: Jongsun
authors: J
authors: Park
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D017209:Apoptosis; D053477:Apoptotic Protease-Activating Factor 1 / Q000378:metabolism; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D008928:Mitochondria / Q000737:chemistry; D010766:Phosphorylation; D019311:Staurosporine / Q000494:pharmacology; D013869:Thiolester Hydrolases; D014638:Vanadates / Q000494:pharmacology
chemical_list: C506592:APAF1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D053477:Apoptotic Protease-Activating Factor 1; D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; C076715:pervanadate; D014638:Vanadates; C437985:THEM4 protein, human; D013869:Thiolester Hydrolases; D019311:Staurosporine