eIF4F: a retrospective.
The original purification of the heterotrimeric eIF4F was published over 30 years ago (Grifo, J. A., Tahara, S. M., Morgan, M. A., Shatkin, A. J., and Merrick, W. C. (1983) J. Biol. Chem. 258, 5804-5810). Since that time, numerous studies have been performed with the three proteins specifically required for the translation initiation of natural mRNAs, eIF4A, eIF4B, and eIF4F. These have involved enzymatic and structural studies of the proteins and a number of site-directed mutagenesis studies. The regulation of translation exhibited through the mammalian target of rapamycin (mTOR) pathway is predominately seen as the phosphorylation of 4E-BP, an inhibitor of protein synthesis that functions by binding to the cap binding subunit of eIF4F (eIF4E). A hypothesis that requires the disassembly of eIF4F during translation initiation to yield free subunits (eIF4A, eIF4E, and eIF4G) is presented.
From the Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4935 wcm2@case.edu.
William C
WC
Merrick
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins; D039601:Eukaryotic Initiation Factor-4A / Q000378:metabolism; D039562:Eukaryotic Initiation Factor-4F / Q000378:metabolism*; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D008954:Models, Biological; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D011487:Protein Conformation; D020365:RNA Helicases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D039562:Eukaryotic Initiation Factor-4F; D039642:Eukaryotic Initiation Factors; D005656:Fungal Proteins; D010750:Phosphoproteins; C031799:eIF-4B; D039601:Eukaryotic Initiation Factor-4A; D020365:RNA Helicases
4E-BP; RNA helicase; eIF4F; eukaryotic initiation factor 4A (eIF4A); eukaryotic initiation factor 4B (eIF4B); eukaryotic translation initiation; initiation factor recycling; mRNA; protein assembly; translation initiation