Ribavirin enhances interferon signaling via stimulation of mTOR and p53 activities.
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.
Su
Wen-Cheng
WC
Graduate Institute of Molecular Medicine, College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan.
Liu
Wei-Liang
WL
Cheng
Ching-Wei
CW
Chou
Yu-Bin
YB
Hung
Ko-Hsuan
KH
Huang
Wen-Hung
WH
Wu
Chao-Liang
CL
Li
Yuan-Tsung
YT
Shiau
Ai-Li
AL
Lai
Ming-Yang
MY
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*
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