Ribavirin targets eIF4E dependent Akt survival signaling.

ABSTRACT: The eukaryotic translation initiation factor eIF4E is dysregulated in many cancers. eIF4E, through its mRNA export and translation functions, combinatorially modulates the expression of genes involved in Akt dependent survival signaling. For these activities, eIF4E must bind the 7-methyl guanosine (m(7)G) cap moiety on the 5'-end of mRNAs. We demonstrate that a physical mimic of the m(7)G cap, ribavirin, inhibits eIF4E dependent Akt survival signaling. Specifically, ribavirin impairs eIF4E mediated Akt activation via inhibiting the production of an upstream activator of Akt, NBS1. Consequently, ribavirin impairs eIF4E dependent apoptotic rescue. A ribavirin analog with distinct physico-chemical properties, tiazofurin, does not impair eIF4E activity indicating that only analogs that mimic t

SUBMITTER: Tan K 

PROVIDER: S-EPMC2573464 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature