title: Irciniastatin A induces potent and sustained activation of extracellular signal-regulated kinase and thereby promotes ectodomain shedding of tumor necrosis factor receptor 1 in human lung carcinoma A549 cells.
abstract: Irciniastatin A is a pederin-type marine product that potently inhibits translation. We have recently shown that irciniastatin A induces ectodomain shedding of tumor necrosis factor (TNF) receptor 1 with slower kinetics than other translation inhibitors. In human lung carcinoma A549 cells, irciniastatin A induced a marked and sustained activation of extracellular signal-regulated kinase (ERK) and induced little activation of p38 mitogen-activated protein (MAP) kinase and c-Jun N-terminal kinase (JNK). Moreover, the TNF receptor 1 shedding induced by irciniastatin A was blocked by the MAP kinase/ERK kinase inhibitor U0126, but not by the p38 MAP kinase inhibitor SB203580 or the JNK inhibitor SP600125. Thus unlike other translation inhibitors that trigger ribotoxic stress response, our results show that irciniastatin A is a unique translation inhibitor that induces a potent and sustained activation of the ERK pathway, and thereby promotes the ectodomain shedding of TNF receptor 1 in A549 cells.
authors.affiliation: Department of Applied Biology, Kyoto Institute of Technology.
authors.forename: Hue Tu
authors.initials: HT
authors.lastname: Quach
authors.forename: Seiya
authors.initials: S
authors.lastname: Hirano
authors.forename: Sayuri
authors.initials: S
authors.lastname: Fukuhara
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Watanabe
authors.forename: Naoki
authors.initials: N
authors.lastname: Kanoh
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Iwabuchi
authors.forename: Takeo
authors.initials: T
authors.lastname: Usui
authors.forename: Takao
authors.initials: T
authors.lastname: Kataoka
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001688:Biological Products / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003374:Coumarins / Q000494:pharmacology / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011161:Porifera / Q000737:chemistry*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D015398:Signal Transduction; D047990:TNF Receptor-Associated Factor 1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D003374:Coumarins; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D047990:TNF Receptor-Associated Factor 1; C498383:psymberin; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases