• Cleavage of eIF4G, a protein scaffold of eIF4F, by sequence specific proteases 2A protease or L-protease, will result in highly inhibited HAV IRES activity. (wikipedia.org)
  • The RNA helicase eIF4A and the scaffold protein eukaryotic translation initiation factor 4G (eIF4G) and the capping protein eIF4E are part of the complex that loads the mRNAs onto the 40 S ribosomal subunit, together with eIF3. (biosyn.com)
  • PDCD4 is composed of two MA3 domains that share similarity with the single MA3 domain present in the eukaryotic translation initiation factor (eIF) 4G, which serves as a scaffold protein to assemble several initiation factors needed for the recruitment of the 40S ribosomal subunit to an mRNA. (biomedcentral.com)
  • eIF4 (eukaryotic initiation factor 4) as a whole complex made up of eIF4A, eIF4B, eIF4E, and eIF4G. (wikipedia.org)
  • The requirement of an intact eIF4G for IRES initiation is specific to HAV IRES among other picornaviruses. (wikipedia.org)
  • 4E-binding proteins (4E-BPs) block the interaction of eIF4E with eIF4G to negatively regulate the formation of the eIF4F complex. (biosyn.com)
  • The 'closed-loop' model explains that the induction of 5'- to 3'-proximity of mRNAs requires the initiation factors eIF4E, eIF4G, and PABP. (biosyn.com)
  • Although eIF4A is an ATP-dependent RNA helicase that binds the MA3 domain of eIF4G to promote translation initiation, binding of eIF4A to the MA3 domains of PDCD4 inhibits protein synthesis. (biomedcentral.com)
  • eIF4F, which is composed of eIF4E, eIF4A, and eIF4G, is required to promote 40 S subunit binding to an mRNA. (biomedcentral.com)
  • eIF4F is used to refer to the complex that comprises eIF4E, 4G, and 4A. (wikipedia.org)
  • Another method to inactivate eIF4F activity is through the effects of the m7GpppG cap analogue, which targets eIF4E and is then able to prevent its association with capped 5' ends of mRNAs. (wikipedia.org)
  • Figure 3 shows molecular models of the cystal structure of eIF4E, in complex with the cap m7GpppA, and a 4EBP1 peptide. (biosyn.com)
  • While eIF4E binds to the 5′-cap structure, eIF4A is an ATP-dependent RNA helicase that hydrolyzes ATP in order to unwind secondary structure present in the 5′-leader of an mRNA that would otherwise inhibit 40S subunit scanning during its search for the initiation codon [ 2 ]. (biomedcentral.com)
  • Eukaryotic translation initiation factors (eIFs) are crucial in the initiation of protein translation. (cbmed.at)
  • Although the bacterial 30 S ribosomal subunit can identify the initiation codon through base-pairing between the 3′-end of its16 S ribosomal RNA subunit and the Shine-Dalgarno sequence upstream of the initiation codon, the 40 S ribosomal subunit of the eukaryotic 80 S ribosome requires several translation initiation factors (eIFs) for its binding to an mRNA and to identify the initiation codon [ 1 - 3 ]. (biomedcentral.com)
  • In cap-dependent translation initiation, the eIF4F binds to the m7G cap on the 5' UTR end, recruiting the 40S small ribosomal subunit and scanning downstream for the AUG start codon. (wikipedia.org)
  • The IRES achieves this by mediating the internal initiation of translation by recruiting a ribosomal 40S pre-initiation complex directly to the initiation codon and eliminates the requirement for eukaryotic initiation factor, eIF4F. (wikipedia.org)
  • A host cell protein found widely and exclusively in eukaryotic cells, La protein binds directly to specific regions on the HAV IRES during mRNA translation as well as RNA replication. (wikipedia.org)
  • Initially, the identified 5' UTR of poliovirus (PV) that directed internal initiation for protein synthesis was termed ribosome landing pad (RLP). (wikipedia.org)
  • Cap-independent internal initiation of protein synthesis differs from normal cellular cap-dependent translation initiation. (wikipedia.org)
  • Although HAV IRES structure has affinity for eIF4F, its affinity is not nearly as high as the host cell's capped mRNAs. (wikipedia.org)
  • Structural complexes between proteins and their substrates can be studied in the gas-phase to determine equilibrium dissociation constants. (biosyn.com)
  • Cap-independent internal initiation has shown to interfere with either parts of eIF4 or the entire complex. (wikipedia.org)
  • Because eIF4F plays an essential role for HAV IRES initiation, it is a target for suppression of IRES. (wikipedia.org)
  • Unfortunately, HAV IRES initiation of translation is not as efficient as a typical host cell m7G cap. (wikipedia.org)
  • The RNA helicase eIF4A plays a key role in unwinding of mRNA and scanning during translation initiation. (nih.gov)
  • However, the structure of the helicase complex and the mechanisms of stimulation of eIF4A activity have remained elusive. (nih.gov)
  • Here we report the topology of the eIF4A/4G/4H helicase complex, which is built from multiple experimentally observed domain-domain contacts. (nih.gov)
  • Taken together, our results indicate a role for the novel DDX3-CBC-eIF3 translational complex in promoting metastasis. (aacrjournals.org)
  • In cap-dependent translation initiation, the eIF4F binds to the m7G cap on the 5' UTR end, recruiting the 40S small ribosomal subunit and scanning downstream for the AUG start codon. (wikipedia.org)
  • 9. Functional dissection of eukaryotic initiation factor 4F: the 4A subunit and the central domain of the 4G subunit are sufficient to mediate internal entry of 43S preinitiation complexes. (nih.gov)
  • The IRES achieves this by mediating the internal initiation of translation by recruiting a ribosomal 40S pre-initiation complex directly to the initiation codon and eliminates the requirement for eukaryotic initiation factor, eIF4F. (wikipedia.org)
  • 1. Eukaryotic translation initiation factor 4E availability controls the switch between cap-dependent and internal ribosomal entry site-mediated translation. (nih.gov)
  • 14. A new translational regulator with homology to eukaryotic translation initiation factor 4G. (nih.gov)
  • 17. Phosphorylation states of translational initiation factors affect mRNA cap binding in wheat. (nih.gov)
  • Altogether these data demonstrate an essential role for the translational factor eIF4G1 on glucose homeostasis and β-cell function. (diabetesjournals.org)
  • 1. High affinity RNA for mammalian initiation factor 4E interferes with mRNA-cap binding and inhibits translation. (nih.gov)
  • 4. RNA aptamers to mammalian initiation factor 4G inhibit cap-dependent translation by blocking the formation of initiation factor complexes. (nih.gov)
  • Unfortunately, HAV IRES initiation of translation is not as efficient as a typical host cell m7G cap. (wikipedia.org)
  • 12. Regulation of cap-dependent translation initiation in the early stage porcine parthenotes. (nih.gov)
  • 13. Modulation of eukaryotic mRNA stability via the cap-binding translation complex eIF4F. (nih.gov)
  • 3. Was the initiation of translation in early eukaryotes IRES-driven? (nih.gov)
  • 7. Internal initiation of translation mediated by the 5' leader of a cellular mRNA. (nih.gov)
  • 8. Manipulation of the host translation initiation complex eIF4F by DNA viruses. (nih.gov)
  • 11. Cap and polyA tail enhance translation initiation at the hepatitis C virus internal ribosome entry site by a discontinuous scanning, or shunting, mechanism. (nih.gov)
  • 13. Cap-independent translation conferred by the 5' leader of tobacco etch virus is eukaryotic initiation factor 4G dependent. (nih.gov)
  • 18. Eukaryotic translation initiation factor 4GI and p97 promote cellular internal ribosome entry sequence-driven translation. (nih.gov)
  • A trimeric peptide initiation factor complex that associates with the 5' MRNA cap structure of RNA ( RNA CAPS ) and plays an essential role in MRNA TRANSLATION . (nih.gov)
  • Translation elongation factor-1 α , La, and PTB interact with the 3′ untranslated region of dengue 4 virus RNA. (microbiologyresearch.org)
  • We recently reported that mTOR inhibitors induce apoptosis via ER stress and the extrinsic pathway upon acute inhibition of the eIF4F complex in colon cancer cells and xenografts, while mutant BRAF600E leads to therapeutic resistance via ERK-mediated Mcl-1 stabilization. (oncotarget.com)
  • Maximal measured disruption of the eIF4F complex occurred under combined mTORC1 and mTORC2 inhibition, whilst combined inhibition of both RAS/ERK and PI3K/AKT pathways in parallel resulted in greater inhibition of eIF4F formation than individually. (biomedcentral.com)
  • Because eIF4F plays an essential role for HAV IRES initiation, it is a target for suppression of IRES. (wikipedia.org)
  • In a 2008 study, cytoplasmic La was observed to reduce HAV IRES initiation. (wikipedia.org)
  • 19. Eukaryotic initiation factor 4E variants alter the morphology, proliferation, and colony-formation properties of MDA-MB-435 cancer cells. (nih.gov)
  • The topology of the complex and the spatial arrangement of the RNA-binding surfaces offer insights into their roles in stimulation of helicase activity and the mechanisms of mRNA unwinding and scanning. (nih.gov)
  • We are particularly interested in mechanisms of assembly and how kinetics and equilibria influence the final composition of assembly complexes and ultimately biological function. (cuny.edu)
  • Cap-independent internal initiation has shown to interfere with either parts of eIF4 or the entire complex. (wikipedia.org)