A novel apoptotic pathway of 3'-Ethynylcytidine(ECyd) involving the inhibition of RNA synthesis--the possibility of RNase L activated pathway as a target of ECyd.

Tomoharu Naito, Tatsushi Yokogawa, Hye-Sook Kim, Akira Matsuda, Takuma Sasaki, Masakazu Fukushima, Yukio Kitade, Yusuke Wataya

Research output: Contribution to journalArticle

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Abstract

RNase L functions as a tumor suppressor protein due to its role in apoptosis during viral infections and various agents treatment. RNase L-mediated apoptosis is accompanied by cytochrome c release from mitochondria and requires caspase-3 activity. It was reported that RNase L is involved in JNK activation during viral infections, and that JNK is essential for apoptosis in response to RNase L activation. However, the proximal signals of RNase L that trigger JNK activation have not as yet been identified, and it is possible that the interactions between RNase L and other proteins play an important role in the RNase L-JNK apoptotic signal pathway. To investigate this hypothesis, we attempted to identify the proteins associated with RNase L using coimmunoprecipitation. In this study, we found that RNase L was associated with other proteins. Here we identified the protein X by LC-MS/MS analysis. We demonstrated that this association was increased in the presence of activated RNase L. Moreover, Protein X was phosphorylated during the activation of RNase L by treatment with cytotoxic agent, ECyd, 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl) cytosine and 2-5A. To reveal the role of protein X in RNase L-mediated apoptosis, we decreased the level of protein X by a small interfering RNA (siRNA). As a result, protein X deficient cells became resistant to the apoptosis mediated by RNase L, suggesting that protein X is related to RNase L-mediated apoptosis following JNK activation. Therefore, in this study, we report the identification of a novel protein, protein X that transduces between RNase L and JNK signals.

Original languageEnglish
Pages (from-to)435-436
Number of pages2
JournalNucleic acids symposium series (2004)
Issue number51
Publication statusPublished - 2007

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RNA
Proteins
Apoptosis
2-5A-dependent ribonuclease
1-(3-C-ethynylribopentofuranosyl)cytosine
Virus Diseases
Tumor Suppressor Proteins
Cytotoxins
Cytochromes c
Caspase 3
Small Interfering RNA
Signal Transduction
Mitochondria

ASJC Scopus subject areas

  • Medicine(all)

Cite this

A novel apoptotic pathway of 3'-Ethynylcytidine(ECyd) involving the inhibition of RNA synthesis--the possibility of RNase L activated pathway as a target of ECyd. / Naito, Tomoharu; Yokogawa, Tatsushi; Kim, Hye-Sook; Matsuda, Akira; Sasaki, Takuma; Fukushima, Masakazu; Kitade, Yukio; Wataya, Yusuke.

In: Nucleic acids symposium series (2004), No. 51, 2007, p. 435-436.

Research output: Contribution to journalArticle

Naito, Tomoharu ; Yokogawa, Tatsushi ; Kim, Hye-Sook ; Matsuda, Akira ; Sasaki, Takuma ; Fukushima, Masakazu ; Kitade, Yukio ; Wataya, Yusuke. / A novel apoptotic pathway of 3'-Ethynylcytidine(ECyd) involving the inhibition of RNA synthesis--the possibility of RNase L activated pathway as a target of ECyd. In: Nucleic acids symposium series (2004). 2007 ; No. 51. pp. 435-436.
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