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Molecular mechanism of the dual activity of 4EGI-1: Dissociating eIF4G from eIF4E but stabilizing the binding of unphosphorylated 4E-BP1
- Sekiyama, Naotaka, Arthanari, Haribabu, Papadopoulos, Evangelos, Rodriguez-Mias, Ricard A., Wagner, Gerhard, Lééger-Abraham, Mélissa
- Proceedings of the National Academy of Sciences of the United States of America 2015 v.112 no.30 pp. E4036
- antineoplastic activity, cell proliferation, messenger RNA, protein subunits, ribosomal proteins, scaffolding proteins, signal transduction, translation (genetics)
- Translation initiation governs many cellular processes, including cell proliferation, growth, and development. Central to this process is the translation initiation factor 4E (eIF4E), which recruits the small ribosomal subunit to the 5′ end of the mRNA through its interaction with the scaffold protein eIF4G. The eIF4E/eIF4G interaction is highly regulated by competitive binding of 4E-binding proteins (4E-BPs), which are at a convergence point of signaling pathways and act as tumor suppressors. The recently discovered eIF4E/eIF4G interaction inhibitor 1 (4EGI-1) dissociates eIF4G but enhances 4E-BP1 binding and has antitumor activity. Here, we elucidate the mechanism for the dual activity of 4EGI-1—it dissociates eIF4G from eIF4E but stabilizes the binding of 4E-BP1.