Disease relevance of KIAA0664

• To test the effects of the VPg- eIF3 interaction on translation, VPg was added to cell-free translation reactions programmed with either capped reporter RNA, an RNA containing an EMCV internal ribosomal entry site (IRES) or an RNA with a cricket paralysis virus IRES [1].
• Initiation on the hepatitis C virus IRES is even simpler: 43S complexes containing only eIF2 and eIF3 bind directly to the initiation codon as a result of specific interaction of the IRES and the 40S subunit [2].
• Rhinovirus 2A protease and foot-and-mouth-disease virus L protease were used to analyze the association of eIF4G with eIF4A, eIF4E, and eIF3 [3].
• The cleavage of the p220 subunit of eukaryotic initiation factor 4F (eIF-4F) that is induced by the poliovirus protease 2A has been shown previously to require another translation initiation factor, eIF-3 [4].
• CONCLUSION: Iron promotes the translation of HCV by stimulating the expression of eIF3, which may be one reason for the negative association between liver iron overload and HCV infection [5].

High impact information on KIAA0664

• Cell stimulation promotes mTOR/raptor binding to the eIF3 complex and phosphorylation of S6K1 at its hydrophobic motif [6].
• The levels of initiation factors eIF-2, eIF-3, eIF-4A, and eIF-4B were quantitated by immunoblotting; all are enriched in the cytoskeletal fraction relative to the soluble fraction [7].
• The eIF3 binds to the 40S ribosome and promotes recruitment of the ternary complex; however, physical contact between eIF3 and eIF2 has not been observed [8].
• The binding site of eIF4E resides in the N-terminal third of eIF4G, while eIF4A and eIF3 binding sites are present in the C-terminal two-thirds [9].
• On the other hand, when the messenger alone or with core eIF3 is taken up by the cells, it is found only on small polysomes [10].

Biological context of KIAA0664

• However, deletion of PCI8 had no discernible effect on cell growth or translation initiation as judged by polysome analysis, suggesting that Pci8p is not required for the essential function of eIF3 in translation initiation [11].
• We demonstrate that the eIF3 p47 can interact with CDK11 in vitro and in vivo, and the interaction can be strengthened by stimulation of apoptosis [12].
• The amino acid sequence deduced from the cDNA agrees with the sequences of CNBr fragments of eIF-3, confirming the identity of the clone [13].
• A fission yeast homolog of Int-6, the mammalian oncoprotein and eIF3 subunit, induces drug resistance when overexpressed [14].
• Through a screen to identify genes that induce multi-drug resistance when overexpressed, we have identified a fission yeast homolog of Int-6, a component of the human translation initiation factor eIF3 [14].

Anatomical context of KIAA0664

• Eukaryotic initiation factor 3 (eIF3), encapsulated in liposomes, is taken up by chick muscle cells in culture [10].
• This "restoring factor" has now been purified from a high-salt wash of rabbit reticulocyte ribosomes by taking advantage of its tight association with factor eIF-3 at low salt concentrations [15].
• Changes in ribosomal binding activity of eIF3 correlate with increased translation rates during activation of T lymphocytes [16].
• Since many initiation factors are strongly conserved between mammalian and yeast systems, we employed a mammalian assay for initiation, the synthesis of methionyl-puromycin, to detect eIF-3 activity in yeast subcellular fractions [17].
• An antiserum was raised against human eIF-3 and used to analyze the eIF-3 subunit composition in poliovirus-infected and uninfected HeLa cells and after incubation of eIF-3 in vitro with viral 2A protease [4].

Associations of KIAA0664 with chemical compounds

• Liposome-encapsulated core eIF3 delivered to cells is found predominantly in 40S ribosomal subunits and gives only a slight stimulation of total protein synthesis [10].
• A region rich in aspartic acid, arginine, tyrosine, and glycine (DRYG) mediates eukaryotic initiation factor 4B (eIF4B) self-association and interaction with eIF3 [18].
• Eukaryotic initiation factor 2 (eIF2), eIF3, and eIF4F were required for initiation; eIF4B and to a lesser extent the pyrimidine tract-binding protein stimulated this process [19].
• Using sucrose density gradient centrifugation to analyze ribosome complexes, we find that most eIF3 is not bound to 40 S ribosomal subunits in unactivated T lymphocytes but becomes ribosome-bound following activation [16].
• Glycerol gradient centrifugation and polyacrylamide gel electrophoresis under nondenaturing conditions indicate that the eIF-3 prepared in this manner is at least 85% pure [20].

Physical interactions of KIAA0664

• They indicate that eIF-3 might play a direct role in cap binding and suggest that poliovirus-induced cleavage of p220 results in the release of the eIF-4A subunit from eIF-4F and abolishes an association between eIF-4F and eIF-3 which may function during the multifactor steps involved in initiation of cap-mediated translation [21].

Regulatory relationships of KIAA0664

• Next to their well-known roles in the initiation process, eIF-2 and eIF-3 also cross-linked to the 5' cap. eIF-2 stimulated eIF-4B and -4E cross-linking, an observation that has been previously described more extensively [22].

Other interactions of KIAA0664

• Ribosome-derived complexes containing cleaved p220 are no longer associated with eIF-3 or eIF-4A, and a significant amount of cleaved p220 is associated with a unique cytoplasmic cap-binding complex [21].
• Spots identified as eukaryotic initiation factor (eIF) 2 alpha, eIF-2 beta, eIF-2 gamma, eIF-4A, and four eIF-3 proteins of less than 50,000 Da corresponded to moderately abundant lysate proteins [23].
• Five initiation factors, eIF-2, eIF-3, eIF-4A, eIF-4B, and eIF-5, were purified from human HeLa cells [24].
• Eight of the subunits of eIF-3 are iodinated rapidly in vitro; the highest incorporation is into p56 and the lowest incorporation is into p28 [25].
• Determination of the amounts of the initiation factors required for translation in the fractionated system showed that AMV RNA 4 required 2-4-fold lower amounts of eIF-3, eIF-4A, eIF-4F, and eIF-4G than did B alpha A mRNA [26].

Analytical, diagnostic and therapeutic context of KIAA0664

• Both titration and competition experiments were consistent with a 1:1 stoichiometry for eIF3 binding [27].
• Surface plasmon resonance studies showed that three recombinant eIF4G fragments corresponding to amino acids 642-1560, 613-1078, and 975-1078 bound eIF3 with similar kinetics [27].
• It was resolved from eIF-3 by both gel filtration and anion-exchange chromatography [4].
• In SDS-PAGE, the purified Co-eIF-2C preparation and an eIF-3 preparation (purified in Dr. A. Wahba's laboratory) separated into seven similar major polypeptides (Mr 110K, 65K, 63K, 53K, 50K, 43K, and 40K) [28].
• METHODS: eIF3 expression was analyzed by TaqMan polymerase chain reaction, Northern and Western blot analysis of HepG2 cells, and liver biopsies [5].

References