Ribavirin Enhances Interferon Signaling Via Stimulation of Mtor and P53 Activities
Resource
FEBS LETTERS v.583 n.17 pp.2793-2798
Journal
FEBS Letters
Pages
2793-2798
Date Issued
2009
Date
2009
Author(s)
SU, WEN-CHENG
LIU, WEI-LIANG
CHENG, CHING-WEI
WU, CHAO-LIANG
SHIAU, AI-LI
LAI, MING-YANG
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 p 53 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. Structured summary: MINT- 7222801: mTOR ( uniprotkb: P 42345) 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)
Subjects
Ribavirin
mTOR
p53
IFN
SDGs
Other Subjects
alpha interferon; cisplatin; interferon regulatory factor 9; levovirin; mammalian target of rapamycin; protein p53; rapamycin; ribavirin; antineoplastic activity; antiviral activity; apoptosis; article; cell viability; controlled study; cytotoxicity; enzyme activation; growth inhibition; hepatitis C; human; human cell; priority journal; protein protein interaction; signal transduction; upregulation; Animals; Antineoplastic Agents; Antiviral Agents; Cell Line; Cisplatin; Cyclin-Dependent Kinase Inhibitor p21; Humans; Interferon-alpha; Protein Kinases; Ribavirin; Signal Transduction; Sirolimus; Tumor Suppressor Protein p53; Mammalia; Raptores