Role of Ribavirin, an Anti-Viral Agent, In Eukaryotic Initiation Factor 4e (Eif4e) Subcellular Localization and Function

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2008-05-13

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Hsiung, Ying-Fan

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Abstract

Expression of eukaryotic initiation factor 4E (eIF4E) is necessary for active cellular growth and catalysis of the rate-limiting step in cap-dependent protein synthesis3-5. Studies in the past decade have shown that eIF4E contributes to malignancy by selectively facilitating the translation of a specific set of mRNAs, those that generally encode key proteins involved in cellular growth, angiogenesis and survival6-9. Key questions remaining in the field are: (1) what is the mechanism by which eIF4E levels are increased in tumor cells? (2) What is the role of eIF4E in regulating the translation of gene products involved in various aspects of malignancy? Finally, (3) how can eIF4E be exploited as a therapeutic target for human cancer progression? Recently, Kentsis and colleagues10 demonstrated that ribavirin disrupts subcellular organization of eIF4E and suppresses eIF4E-mediated oncogenic transformation of murine cells and tumor growth of a mouse model of eIF4E-dependent human squamous cell carcinoma. These findings suggest a specific and novel mechanism by which ribavirin affects cellular distribution and function of eIF4E, a topic that will be explored in the current proposal. This investigation may facilitate understanding in the regulation of transcription and thus provide a potential strategy for interrupting oncogenic cascades.

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