SP600125 Inhibits Cap-dependent Translation Independently of the c-Jun N-terminal Kinase Pathway

Access this Article

Author(s)

    • Ito Masatoshi
    • Laboratory for Immunogenomics, RIKEN Research Center for Allergy and Immunology|Department of Supramolecular Biology, Graduate School of Nanobioscience, Yokohama City University
    • Kitamura Hiroshi
    • Laboratory for Immunogenomics, RIKEN Research Center for Allergy and Immunology|Department of Comparative and Experimental Medicine, Graduate School of Medical Sciences, Nagoya City University
    • Kikuguchi Chisato
    • Laboratory for Immunogenomics, RIKEN Research Center for Allergy and Immunology
    • Hase Koji
    • Laboratory for Epithelial Immunobiology, RIKEN Research Center for Allergy and Immunology
    • Ohno Hiroshi
    • Laboratory for Epithelial Immunobiology, RIKEN Research Center for Allergy and Immunology|Department of Supramolecular Biology, Graduate School of Nanobioscience, Yokohama City University
    • Ohara Osamu
    • Laboratory for Immunogenomics, RIKEN Research Center for Allergy and Immunology|Department of Human Genome Research, Kazusa DNA Research Institute

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.<br>

Journal

  • Cell Structure and Function

    Cell Structure and Function 36(1), 27-33, 2011

    Japan Society for Cell Biology

Codes

  • NII Article ID (NAID)
    130004137561
  • Text Lang
    ENG
  • ISSN
    0386-7196
  • Data Source
    J-STAGE 
Page Top