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

Research output: Contribution to journalArticle

22 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 2010

Fingerprint

ras GTPase-Activating Proteins
ras Proteins
Amino Acid Motifs
Ribonucleases
Cells
Apoptosis
Cell Line
Phosphorylation
Neoplasms
Proteins
Phosphotransferases
Endoribonucleases
RNA Polymerase I
Apoptosis Regulatory Proteins
JNK Mitogen-Activated Protein Kinases
Cytosine
Virus Diseases
Immunoprecipitation
Proteomics
Small Interfering RNA

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Association of RNase L with a Ras GTPase-activating-like protein IQGAP1 in mediating the apoptosis of a human cancer cell-line. / Sato, Akira; Naito, Tomoharu; Hiramoto, Akiko; Goda, Kazato; Omi, Takuya; Kitade, Yukio; Sasaki, Takuma; Matsuda, Akira; Fukushima, Masakazu; Wataya, Yusuke; Kim, Hye-Sook.

In: FEBS Journal, Vol. 277, No. 21, 11.2010, p. 4464-4473.

Research output: Contribution to journalArticle

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, vol. 277, no. 21, pp. 4464-4473. https://doi.org/10.1111/j.1742-4658.2010.07833.x
Sato, Akira ; Naito, Tomoharu ; Hiramoto, Akiko ; Goda, Kazato ; Omi, Takuya ; Kitade, Yukio ; Sasaki, Takuma ; Matsuda, Akira ; Fukushima, Masakazu ; Wataya, Yusuke ; Kim, Hye-Sook. / Association of RNase L with a Ras GTPase-activating-like protein IQGAP1 in mediating the apoptosis of a human cancer cell-line. In: FEBS Journal. 2010 ; Vol. 277, No. 21. pp. 4464-4473.
@article{a31649e78ee84a518b535ddf612e65da,
title = "Association of RNase L with a Ras GTPase-activating-like protein IQGAP1 in mediating the apoptosis of a human cancer cell-line",
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.",
keywords = "Apoptosis, ECyd, Focused proteomics, IQGAP1, RNase L",
author = "Akira Sato and Tomoharu Naito and Akiko Hiramoto and Kazato Goda and Takuya Omi and Yukio Kitade and Takuma Sasaki and Akira Matsuda and Masakazu Fukushima and Yusuke Wataya and Hye-Sook Kim",
year = "2010",
month = "11",
doi = "10.1111/j.1742-4658.2010.07833.x",
language = "English",
volume = "277",
pages = "4464--4473",
journal = "FEBS Journal",
issn = "1742-464X",
publisher = "Wiley-Blackwell",
number = "21",

}

TY - JOUR

T1 - Association of RNase L with a Ras GTPase-activating-like protein IQGAP1 in mediating the apoptosis of a human cancer cell-line

AU - Sato, Akira

AU - Naito, Tomoharu

AU - Hiramoto, Akiko

AU - Goda, Kazato

AU - Omi, Takuya

AU - Kitade, Yukio

AU - Sasaki, Takuma

AU - Matsuda, Akira

AU - Fukushima, Masakazu

AU - Wataya, Yusuke

AU - Kim, Hye-Sook

PY - 2010/11

Y1 - 2010/11

N2 - 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.

AB - 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.

KW - Apoptosis

KW - ECyd

KW - Focused proteomics

KW - IQGAP1

KW - RNase L

UR - http://www.scopus.com/inward/record.url?scp=79952108946&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952108946&partnerID=8YFLogxK

U2 - 10.1111/j.1742-4658.2010.07833.x

DO - 10.1111/j.1742-4658.2010.07833.x

M3 - Article

C2 - 20875083

AN - SCOPUS:79952108946

VL - 277

SP - 4464

EP - 4473

JO - FEBS Journal

JF - FEBS Journal

SN - 1742-464X

IS - 21

ER -