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Association of RNase L with a Ras GTPase‐activating‐like protein IQGAP1 in mediating the apoptosis of a human cancer cell‐line
Author(s) -
Sato Akira,
Naito Tomoharu,
Hiramoto Akiko,
Goda Kazato,
Omi Takuya,
Kitade Yukio,
Sasaki Takuma,
Matsuda Akira,
Fukushima Masakazu,
Wataya Yusuke,
Kim HyeSook
Publication year - 2010
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2010.07833.x
Subject(s) - iqgap1 , apoptosis , gtpase , microbiology and biotechnology , rnase p , biology , cancer research , signal transduction , gene , genetics , scaffold protein , rna
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. Structured digital abstract• MINT‐7990574 : RNaseL (uniprotkb: Q05823 ) physically interacts ( MI:0914 ) with Kinesin‐like protein KIF23 (uniprotkb: Q02241 ) and Ras GTPase‐activating‐like protein IQGAP1 (uniprotkb: P46940 ) by anti bait coimmunoprecipitation ( MI:0006 ) • MINT‐7990598 : RNaseL (uniprotkb: Q05823 ) physically interacts ( MI:0915 ) with IQGAP1 (uniprotkb: P46940 ) by anti bait coimmunoprecipitation ( MI:0006 )