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

• 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

Keywords

• SP600125
• cap-dependent translation
• polysome
• c-Jun N-terminal kinase

Details

• CRID: 1390282679672247168
• NII Article ID: 130004137561
• NII Article ID: 40019163801
• NII Book ID: AA0060007X
• DOI: 10.1247/csf.10025
• ISSN: 13473700
• ISSN: 03867196
• NDL BIB ID: 023442632
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I023442632
• Web Site: http://www.jstage.jst.go.jp/article/csf/36/1/36_10025/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2013092010
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed