title: Cyclophilin A as a downstream effector of PI3K/Akt signalling pathway in multiple myeloma cells.
abstract: Cyclophilin A (Cyp A), a member of the peptidyl-prolyl isomerase (PPI) family, may function as a molecular signalling switch. Comparative proteomic studies have identified Cyp A as a potential downstream target of protein kinase B (Akt). This study confirmed that Cyp A is a downstream effector of the phosphatidylinositide 3-kinase (PI3K)/Akt signalling pathway. Cyp A was highly phosphorylated in response to interleukin-6 treatment, which was consistent with the accumulation of phosphorylated Akt, suggesting that Cyp A is a phosphorylation target of Akt and downstream effector of the PI3K/Akt pathway. Cyclosporine A (CsA), a PPI inhibitor, inhibited the growth of multiple myeloma (MM) U266 cells. Moreover, CsA treatment inhibited the activation of the signal transducer and activator of transcription 3 (STAT3) in MM U266 cells. Several Cyp A mutants were generated. Mutants with mutated AKT phosphorylation sites increased the G1 phase arrest in MM U266 cells. The other mutants that mimicked the phosphorylated state of Cyp A decreased the percentage of G1 phase. These results demonstrated that the states of phosphorylation of Cyp A by Akt can influence the progress of the cell cycle in MM U266 cells and that this effect is probably mediated through the Janus-activated kinase 2/STAT3 signalling pathway.
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan.
authors.forename: Zuo-Lin
authors.initials: ZL
authors.lastname: Lin
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan.
authors.forename: Hsin-Jou
authors.initials: HJ
authors.lastname: Wu
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan.
authors.forename: Jin-An
authors.initials: JA
authors.lastname: Chen
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan.
authors.forename: Kuo-Chih
authors.initials: KC
authors.lastname: Lin
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan.
authors.forename: Jung-Hsin
authors.initials: JH
authors.lastname: Hsu
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D021984:Cyclophilin A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D004252:DNA Mutational Analysis; D006801:Humans; D062385:Hydroxybenzoates / Q000494:pharmacology; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D009581:Nitrofurans / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D062385:Hydroxybenzoates; D050505:Mutant Proteins; D009581:Nitrofurans; D050796:STAT3 Transcription Factor; D016572:Cyclosporine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D021984:Cyclophilin A; C013150:nifuroxazide
keywords: AKT; JAK2; STAT3; cyclophilin A; interleukin-6; multiple myeloma