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

Hue Tu Quach, Seiya Hirano, Sayuri Fukuhara, Tsubasa Watanabe, Naoki Kanoh, Yoshiharu Iwabuchi, Takeo Usui, Takao Kataoka

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)941-946
Number of pages6
JournalBiological and Pharmaceutical Bulletin
Volume38
Issue number6
DOIs
Publication statusPublished - 2015 Jun 1

Keywords

  • Extracellular signal-regulated kinase
  • Irciniastatin A
  • P38 mitogen-activated protein kinase
  • Ribotoxic stress response
  • Translation inhibitor
  • Tumor necrosis factor receptor 1

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this