Association of RNase L with a Ras GTPase-activating-like protein IQGAP1 in mediating the apoptosis of a human cancer cell-line

Akira Sato, Tomoharu Naito, Akiko Hiramoto, Kazato Goda, Takuya Omi, Yukio Kitade, Takuma Sasaki, Akira Matsuda, Masakazu Fukushima, Yusuke Wataya, Hye Sook Kim

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23 Citations (Scopus)

Abstract

Mammalian intracellular ribonuclease L (RNase L) is a latent endoribonuclease that functions against viral infections as an apoptosis-inducing protein, and its activity requires intracellular 5′-end-triphosphorylated-2′,5′ oligoadenylates (2-5A) as an activator. Previously, we showed that RNase L can be activated in human cancer cell line HT1080 by an RNA polymerase I inhibitor, 1-(3-C-ethynyl-β-D-ribo- pentofuranosyl)cytosine (3′-ethynylcytidine; ECyd). In ECyd-treated cells, knockdown of the RNase L resulted in a marked decrease in c-jun N-terminal kinase (JNK) phosphorylation, thereby inhibiting apoptosis. We investigate RNase L binding partners by focused proteomic approach using immunoprecipitation with anti-RNase L IgG and mass spectrometry. We found that the IQ motif-containing Ras GTPase-activating-like protein 1 (IQGAP1) can associate with RNase L, and that phosphorylation occurs on the IQGAP1. ECyd-induced JNK phosphorylation and apoptosis were inhibited when IQGAP1 was knocked down with a small interfering RNA. These results raise the interesting possibility that the RNase L-IQGAP1 association may regulate JNK phosphorylation in RNase L-madiated apoptosis. It is likely IQGAP1 works as a regulator in apoptosis.

Original languageEnglish
Pages (from-to)4464-4473
Number of pages10
JournalFEBS Journal
Volume277
Issue number21
DOIs
Publication statusPublished - Nov 1 2010

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Keywords

  • Apoptosis
  • ECyd
  • Focused proteomics
  • IQGAP1
  • RNase L

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Sato, A., Naito, T., Hiramoto, A., Goda, K., Omi, T., Kitade, Y., Sasaki, T., Matsuda, A., Fukushima, M., Wataya, Y., & Kim, H. S. (2010). Association of RNase L with a Ras GTPase-activating-like protein IQGAP1 in mediating the apoptosis of a human cancer cell-line. FEBS Journal, 277(21), 4464-4473. https://doi.org/10.1111/j.1742-4658.2010.07833.x