Ribavirin enhances interferon signaling via stimulation of mTOR and p53 activities

Wen Cheng Su; Wei Liang Liu; Ching Wei Cheng; Yu Bin Chou; Ko Hsuan Hung; Wen Hung Huang; Chao Liang Wu; Yuan Tsung Li; Ai Li Shiau; Ming Yang Lai

doi:10.1016/j.febslet.2009.07.027

Ribavirin enhances interferon signaling via stimulation of mTOR and p53 activities

Wen Cheng Su, Wei Liang Liu, Ching Wei Cheng, Yu Bin Chou, Ko Hsuan Hung, Wen Hung Huang, Chao Liang Wu, Yuan Tsung Li, Ai Li Shiau, Ming Yang Lai

研究成果: Article › 同行評審

20 引文斯高帕斯（Scopus）

摘要

Cellular mechanisms involving the enhancement of interferon (IFN) signaling by ribavirin remain poorly understood. Here, we identified a novel role of ribavirin in the communication between p53 and the mammalian target of rapamycin (mTOR) signaling. Ribavirin activates p53 by stimulating mTOR and promoting the interaction between mTOR and p53. Activated p53 stimulates the transcription of IFN regulatory factor 9 and subsequently enhances IFN signaling. Furthermore, ribavirin-induced activation of mTOR and p53 enhances IFN-dependent signaling for the IFN-α/ribavirin combined treatment. We conclude that ribavirin enhances activities of mTOR and p53, which may account for its antiviral and antitumor effects. Structured summary: MINT-7222801:. mTOR (uniprotkb:P42345) physically interacts (MI:0914) with raptor (uniprotkb:Q8N122) by anti bait coimmunoprecipitation (MI:0006). MINT-7222793:. mTOR (uniprotkb:P42345) physically interacts (MI:0914) with RICTOR (uniprotkb:Q8N6M7) by anti bait coimmunoprecipitation (MI:0006). MINT-7222784:. mTOR (uniprotkb:P42345) physically interacts (MI:0914) with P53 (uniprotkb:P04637) by anti bait coimmunoprecipitation (MI:0006).

原文	English
頁（從 - 到）	2793-2798
頁數	6
期刊	FEBS Letters
卷	583
發行號	17
DOIs	https://doi.org/10.1016/j.febslet.2009.07.027
出版狀態	Published - 2009 9月 3

All Science Journal Classification (ASJC) codes

生物物理學
結構生物學
生物化學
分子生物學
遺傳學
細胞生物學

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10.1016/j.febslet.2009.07.027

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title = "Ribavirin enhances interferon signaling via stimulation of mTOR and p53 activities",

abstract = "Cellular mechanisms involving the enhancement of interferon (IFN) signaling by ribavirin remain poorly understood. Here, we identified a novel role of ribavirin in the communication between p53 and the mammalian target of rapamycin (mTOR) signaling. Ribavirin activates p53 by stimulating mTOR and promoting the interaction between mTOR and p53. Activated p53 stimulates the transcription of IFN regulatory factor 9 and subsequently enhances IFN signaling. Furthermore, ribavirin-induced activation of mTOR and p53 enhances IFN-dependent signaling for the IFN-α/ribavirin combined treatment. We conclude that ribavirin enhances activities of mTOR and p53, which may account for its antiviral and antitumor effects. Structured summary: MINT-7222801:. mTOR (uniprotkb:P42345) physically interacts (MI:0914) with raptor (uniprotkb:Q8N122) by anti bait coimmunoprecipitation (MI:0006). MINT-7222793:. mTOR (uniprotkb:P42345) physically interacts (MI:0914) with RICTOR (uniprotkb:Q8N6M7) by anti bait coimmunoprecipitation (MI:0006). MINT-7222784:. mTOR (uniprotkb:P42345) physically interacts (MI:0914) with P53 (uniprotkb:P04637) by anti bait coimmunoprecipitation (MI:0006).",

author = "Su, {Wen Cheng} and Liu, {Wei Liang} and Cheng, {Ching Wei} and Chou, {Yu Bin} and Hung, {Ko Hsuan} and Huang, {Wen Hung} and Wu, {Chao Liang} and Li, {Yuan Tsung} and Shiau, {Ai Li} and Lai, {Ming Yang}",

note = "Funding Information: We thank Dr. David Sabatini for providing the shRNA constructs and Dr. Hung-Chih Yang for helpful discussions on the manuscript. This work was supported by grants from the Taiwan National Science Council (93WFA0106311 to Ming-Yang Lai) and Liver Disease Prevention & Treatment Research Foundation (to Wen-Cheng Su).",

year = "2009",

month = sep,

day = "3",

doi = "10.1016/j.febslet.2009.07.027",

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T1 - Ribavirin enhances interferon signaling via stimulation of mTOR and p53 activities

AU - Su, Wen Cheng

AU - Liu, Wei Liang

AU - Cheng, Ching Wei

AU - Chou, Yu Bin

AU - Hung, Ko Hsuan

AU - Huang, Wen Hung

AU - Wu, Chao Liang

AU - Li, Yuan Tsung

AU - Shiau, Ai Li

AU - Lai, Ming Yang

N1 - Funding Information: We thank Dr. David Sabatini for providing the shRNA constructs and Dr. Hung-Chih Yang for helpful discussions on the manuscript. This work was supported by grants from the Taiwan National Science Council (93WFA0106311 to Ming-Yang Lai) and Liver Disease Prevention & Treatment Research Foundation (to Wen-Cheng Su).

PY - 2009/9/3

Y1 - 2009/9/3

N2 - Cellular mechanisms involving the enhancement of interferon (IFN) signaling by ribavirin remain poorly understood. Here, we identified a novel role of ribavirin in the communication between p53 and the mammalian target of rapamycin (mTOR) signaling. Ribavirin activates p53 by stimulating mTOR and promoting the interaction between mTOR and p53. Activated p53 stimulates the transcription of IFN regulatory factor 9 and subsequently enhances IFN signaling. Furthermore, ribavirin-induced activation of mTOR and p53 enhances IFN-dependent signaling for the IFN-α/ribavirin combined treatment. We conclude that ribavirin enhances activities of mTOR and p53, which may account for its antiviral and antitumor effects. Structured summary: MINT-7222801:. mTOR (uniprotkb:P42345) physically interacts (MI:0914) with raptor (uniprotkb:Q8N122) by anti bait coimmunoprecipitation (MI:0006). MINT-7222793:. mTOR (uniprotkb:P42345) physically interacts (MI:0914) with RICTOR (uniprotkb:Q8N6M7) by anti bait coimmunoprecipitation (MI:0006). MINT-7222784:. mTOR (uniprotkb:P42345) physically interacts (MI:0914) with P53 (uniprotkb:P04637) by anti bait coimmunoprecipitation (MI:0006).

AB - Cellular mechanisms involving the enhancement of interferon (IFN) signaling by ribavirin remain poorly understood. Here, we identified a novel role of ribavirin in the communication between p53 and the mammalian target of rapamycin (mTOR) signaling. Ribavirin activates p53 by stimulating mTOR and promoting the interaction between mTOR and p53. Activated p53 stimulates the transcription of IFN regulatory factor 9 and subsequently enhances IFN signaling. Furthermore, ribavirin-induced activation of mTOR and p53 enhances IFN-dependent signaling for the IFN-α/ribavirin combined treatment. We conclude that ribavirin enhances activities of mTOR and p53, which may account for its antiviral and antitumor effects. Structured summary: MINT-7222801:. mTOR (uniprotkb:P42345) physically interacts (MI:0914) with raptor (uniprotkb:Q8N122) by anti bait coimmunoprecipitation (MI:0006). MINT-7222793:. mTOR (uniprotkb:P42345) physically interacts (MI:0914) with RICTOR (uniprotkb:Q8N6M7) by anti bait coimmunoprecipitation (MI:0006). MINT-7222784:. mTOR (uniprotkb:P42345) physically interacts (MI:0914) with P53 (uniprotkb:P04637) by anti bait coimmunoprecipitation (MI:0006).

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JO - FEBS Letters

JF - FEBS Letters

IS - 17

ER -

Ribavirin enhances interferon signaling via stimulation of mTOR and p53 activities

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