Pathway description:
Translation initiation is a complex process in which initiator tRNA, 40S, and 60S ribosomal subunits are assembled by eukaryotic initiation factors (eIFs) into an 80S ribosome at the initiation codon of mRNA. The cap-binding complex eIF4F and the factors eIF4A and eIF4B are required for binding of 43S complexes (comprising a 40S subunit, eIF2/GTP/Met-tRNAi and eIF3) to the 5′ end of capped mRNA but are not sufficient to promote ribosomal scanning to the initiation codon.
The eukaryotic translation initiation factor 4F (eIF4F) mediates 40S ribosomal subunit binding to the 5'end of capped mRNA. eIF4F is a complex containing three proteins: eIF4E, the cap-binding subunit; eIF4A, an RNA-dependent ATPase/ATP-dependent RNA helicase; and eIF4G, a high-molecular-weight protein that acts as a scaffold for binding eIF4E and eIF4A. In addition, eIF4G interacts with the 40S ribosome binding factor eIF3 and the poly(A)-binding protein, thereby establishing a critical link between mRNA and the ribosome. The various eIF4F subunits are expressed to remarkably different levels in most cell types, with the eIF4E subunit being the least abundant.
References:
Anthony, D. D., and W. C. Merrick. (1991) Eukaryotic initiation factor (eIF)-4F. Implications for a role in internal initiation of translation. J. Biol. Chem. 266,10218-10226 Avdulov, S. et al. (2004) Activation of translation complex eIF4F is essential for the genesis and maintenance of the malignant phenotype in human mammary epithelial cells. Cancer Cell 5,553-563.
Gingras, A. C.,et al. (1999) eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation. Annu. Rev. Biochem. 68,913-963.
Hentze, M. W. (1997) eIF4G: a multipurpose ribosome adapter? Science 275,500-501
Hershey, J. W. B., and W. C. Merrick.(2000) Translational control of gene expression Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
