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.
Mesh Terms:
Animals, Antineoplastic Agents, Antiviral Agents, Cell Line, Cisplatin, Cyclin-Dependent Kinase Inhibitor p21, Humans, Interferon-alpha, Protein Kinases, Ribavirin, Signal Transduction, Sirolimus, TOR Serine-Threonine Kinases, Tumor Suppressor Protein p53
Animals, Antineoplastic Agents, Antiviral Agents, Cell Line, Cisplatin, Cyclin-Dependent Kinase Inhibitor p21, Humans, Interferon-alpha, Protein Kinases, Ribavirin, Signal Transduction, Sirolimus, TOR Serine-Threonine Kinases, Tumor Suppressor Protein p53
FEBS Lett.
Date: Sep. 03, 2009
PubMed ID: 19619545
View in: Pubmed Google Scholar
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