SP600125 inhibits cap-dependent translation independently of the c-Jun N-terminal kinase pathway

Masatoshi Ito, Hiroshi Kitamura, Chisato Kikuguchi, Kouji Hase, Hiroshi Ohno, Osamu Ohara

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

We investigated the effects of SP600125 (formerly called c-Jun N-terminal kinase (JNK) inhibitor II) on translation using cultured mouse cells. SP600125 (50 μM) treatment rapidly repressed overall protein synthesis, accompanied by a reduction in the mRNAs for housekeeping genes such as glyceraldehyde-3-phosphate dehydrogenase in the polysomal fraction. SP600125 decreased polysomes with a concomitant increase in free ribosomal subunits in the cytoplasm, suggesting that global translation was inhibited at the initiation step. A reporter analysis using exogenous mRNAs showed that SP600125 inhibited cap-dependent but not internal ribosome entry site-dependent translation. SP600125 significantly attenuated phosphorylation of components in the mTOR pathway, which is responsible for cap-dependent translation. In contrast to SP600125, short hairpin RNAs for JNK1 and JNK2 failed to affect overall protein synthesis. Collectively, SP600125 inhibits cap-dependent translation, independent of the JNK pathway.

Original languageEnglish
Pages (from-to)27-33
Number of pages7
JournalCell Structure and Function
Volume36
Issue number1
DOIs
Publication statusPublished - 2011
Externally publishedYes

Fingerprint

JNK Mitogen-Activated Protein Kinases
Ribosome Subunits
Messenger RNA
Glyceraldehyde-3-Phosphate Dehydrogenases
Polyribosomes
Essential Genes
anthra(1,9-cd)pyrazol-6(2H)-one
Small Interfering RNA
Cultured Cells
Cytoplasm
Proteins
Phosphotransferases
Phosphorylation

Keywords

  • c-jun N-terminal kinase
  • Cap-dependent translation
  • Polysome
  • SP600125

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

SP600125 inhibits cap-dependent translation independently of the c-Jun N-terminal kinase pathway. / Ito, Masatoshi; Kitamura, Hiroshi; Kikuguchi, Chisato; Hase, Kouji; Ohno, Hiroshi; Ohara, Osamu.

In: Cell Structure and Function, Vol. 36, No. 1, 2011, p. 27-33.

Research output: Contribution to journalArticle

Ito, Masatoshi ; Kitamura, Hiroshi ; Kikuguchi, Chisato ; Hase, Kouji ; Ohno, Hiroshi ; Ohara, Osamu. / SP600125 inhibits cap-dependent translation independently of the c-Jun N-terminal kinase pathway. In: Cell Structure and Function. 2011 ; Vol. 36, No. 1. pp. 27-33.
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