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The translational factor eukaryotic initiation factor 4E (eIF4E) is a central component in the initiation and regula-tionof translation ineukaryotic cells.Through its interaction with the 5¢ cap structure of mRNA, eIF4E functions to recruit mRNAs to the ribosome. The accumulation of expressed sequence tag sequences has allowed the identifi-cation of three different eIF4E-familymembers inmammals termed eIF4E-1, eIF4E-2 (4EHP, 4E-LP) and eIF4E-3, which differ in their structural signatures, functional char-acteristics and expression patterns. . | Eur. J. Biochem. 271 2189-2203 2004 FEBS 2004 doi 10.1111 j.1432-1033.2004.04149.x Characterization of mammalian eIF4E-family members Bhavesh Joshi1 Amy Cameron1 and Rosemary Jagus1 2 1 Center of Marine Biotechnology Baltimore MD USA 2Program in Oncology Greenebaum Cancer Center Baltimore MD USA The translational factor eukaryotic initiation factor 4E eIF4E is a central component in the initiation and regulation of translation in eukaryotic cells. Through its interaction with the 5 cap structure of mRNA eIF4E functions to recruit mRNAs to the ribosome. The accumulation of expressed sequence tag sequences has allowed the identification of three different eIF4E-family members in mammals termed eIF4E-1 eIF4E-2 4EHP 4E-LP and eIF4E-3 which differ in their structural signatures functional characteristics and expression patterns. Unlike eIF4E-1 which is found in all eukaryotes orthologues for eIF4E-2 appear to be restricted to metazoans while those for eIF4E-3 have been found only in chordates. Like prototypical eIF4E-1 eIF4E-2 was found to be ubiquitously expressed with the highest levels in the testis. Expression of eIF4E-3 was detected only in heart skeletal muscle lung and spleen. Similarly to eIF4E-1 both eIF4E-2 and eIF4E-3 can bind to the mRNA cap-structure. However in contrast to eIF4E-1 which interacts with both the scaffold protein eIF4G and the translational repressor proteins the eIF4E-binding proteins 4E-BPs eIF4E-2 and eIF4E-3 each possesses a range of partial activities. eIF4E-2 does not interact with eIF4G but does interact with 4E-BPs. Conversely eIF4E-3 interacts with eIF4G but not with 4E-BPs. Neither eIF4E-2 nor eIF4E-3 is able to rescue the lethality of eIF4E gene deletion in yeast. It is hypothesized that each eIF4E-family member fills a specialized niche in the recruitment of mRNAs by the ribosome through differences in their abilities to bind cap and or to interact with eIF4G and the 4E-BPs. Keywords eIF4E family 4EHP 4E-BP eIF4G translation. The
