The binding of eukaryotic ribosomes to mRNA is a complex process that is considered to be rate-limiting in translation initiation, and consequently a key target for translational regulation. Ribosome binding to mRNA is facilitated by the 5' cap structure, m7GpppN (where N is any nucleotide). The initiation factor eIF4F plays a key role in regulating translation rates. eIF4F is a three-subunit complex composed of eIF4E, the cap-binding protein; eIF4A, an RNA helicase; and eIF4G (p220), which bridges eIF4E and eIF4A, and enhances dramatically the interaction of eIF4E with the mRNA 5' cap structure. eIF4F in conjunction with another initiation factor, eIF4B, is thought to unwind the mRNA 5 '-secondary structure to facilitate the binding of mRNA to ribosomes The activity of eIF4F, and the regulation of mRNA binding to ribosomes is tightly correlated with the growth status of the cell. Recently, proteins that interact with eIF4E, termed 4E-BPs, have been identified; these proteins link translation initiation and growth promoting signal transduction pathways. Phosphorylation of 4E-BPs in response to insulin and mitogens decreases their affinity for eIF4E. 4E-BPs compete with eIF4G for binding to eIF4E through binding domains that share common sequence motifs. Consequently, 4E-BPs restrain eIF4E from forming an active cap-binding complex, eIF4F, and prevent subsequent binding of 40S ribosomal subunit to capped mRNAs. Under these conditions, the binding of eIF4E to the mRNA cap structure is extremely inefficient. As a result, cap- and eIF4E-dependent translation is downregulated. Modulation of eIF4F activity is also observed following infection by certain viruses. One of the most dramatic examples of this occurs upon picornaviral infection. As we report here, eIF4G alone is a relatively poor substrate for cleavage by the rhinovirus 2A proteinase (2Apro). However, an eIF4G-eIF4E complex is cleaved efficiently by the 2Apro suggesting that eIF4F is a preferred target for di
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.34730 |
| Date | January 1997 |
| Creators | Haghighat, Ashkan. |
| Contributors | Sonenberg, Nahum (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Biochemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001601619, proquestno: NQ44448, Theses scanned by UMI/ProQuest. |
Page generated in 0.002 seconds