Ribavirin enhances interferon signaling via stimulation of mTOR and p53 activities

Su, Wen-Cheng; Liu, Wei-Liang; Cheng, Ching-Wei; Chou, Yu-Bin; Hung, Ko-Hsuan; Huang, Wen-Hung; Wu, Chao-Liang; Li, Yuan-Tsung; Shiau, Ai-Li; Lai, Ming-Yang

doi:10.1016/j.febslet.2009.07.027

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Volume 583, Issue 17 , Pages 2793-2798, 3 September 2009

Ribavirin enhances interferon signaling via stimulation of mTOR and p53 activities

Edited by Giulio Superti-Furga

Wen-Cheng Su
- Graduate Institute of Molecular Medicine, College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan
Wei-Liang Liu
- Graduate Institute of Clinical Medicine, College of Medicine and Hospital, National Taiwan University, No. 7, Chung-Shan South Rd., Taipei 10002, Taiwan
Ching-Wei Cheng
- Graduate Institute of Molecular Medicine, College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan
Yu-Bin Chou
- Graduate Institute of Clinical Medicine, College of Medicine and Hospital, National Taiwan University, No. 7, Chung-Shan South Rd., Taipei 10002, Taiwan
Ko-Hsuan Hung
- Graduate Institute of Clinical Medicine, College of Medicine and Hospital, National Taiwan University, No. 7, Chung-Shan South Rd., Taipei 10002, Taiwan
Wen-Hung Huang
- Graduate Institute of Clinical Medicine, College of Medicine and Hospital, National Taiwan University, No. 7, Chung-Shan South Rd., Taipei 10002, Taiwan
Chao-Liang Wu
- Departments of Biochemistry, College of Medicine, National Cheng Kung University, Tainan, Taiwan
Yuan-Tsung Li
- Departments of Biochemistry, College of Medicine, National Cheng Kung University, Tainan, Taiwan
Ai-Li Shiau
- Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
Ming-Yang Lai
- Graduate Institute of Clinical Medicine, College of Medicine and Hospital, National Taiwan University, No. 7, Chung-Shan South Rd., Taipei 10002, Taiwan
- Department of Internal Medicine, College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan
- Corresponding author. Address: Graduate Institute of Clinical Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Rd., Taipei 10002, Taiwan. Fax: +886 2 23825962.

Received 7 May 2009; received in revised form 8 July 2009; accepted 14 July 2009. published online 20 July 2009.

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.