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
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- Quach Hue Tu
- Department of Applied Biology, Kyoto Institute of Technology
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- Hirano Seiya
- Department of Applied Biology, Kyoto Institute of Technology
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- Fukuhara Sayuri
- Department of Applied Biology, Kyoto Institute of Technology
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- Watanabe Tsubasa
- Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University
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- Kanoh Naoki
- Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University
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- Iwabuchi Yoshiharu
- Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University
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- Usui Takeo
- Faculty of Life and Environmental Sciences, University of Tsukuba
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- Kataoka Takao
- Department of Applied Biology, Kyoto Institute of Technology
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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.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 38 (6), 941-946, 2015
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679610743040
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- NII論文ID
- 130005072659
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 026408499
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- PubMed
- 26027837
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- 本文言語コード
- en
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