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). © 2009 Federation of European Biochemical Societies.