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-alpha/ribavirin combined treatment. We conclude that ribavirin enhances activities of mTOR and p53, which may account for its antiviral and antitumor effects.
authors.affiliation: Graduate Institute of Molecular Medicine, College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan.
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Su
authors.forename: Wei-Liang
authors.initials: WL
authors.lastname: Liu
authors.forename: Ching-Wei
authors.initials: CW
authors.lastname: Cheng
authors.forename: Yu-Bin
authors.initials: YB
authors.lastname: Chou
authors.forename: Ko-Hsuan
authors.initials: KH
authors.lastname: Hung
authors.forename: Wen-Hung
authors.initials: WH
authors.lastname: Huang
authors.forename: Chao-Liang
authors.initials: CL
authors.lastname: Wu
authors.forename: Yuan-Tsung
authors.initials: YT
authors.lastname: Li
authors.forename: Ai-Li
authors.initials: AL
authors.lastname: Shiau
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Lai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D012254:Ribavirin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016898:Interferon-alpha; D016159:Tumor Suppressor Protein p53; D012254:Ribavirin; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D002945:Cisplatin; D020123:Sirolimus