Conservation and diversity in the structure of translation initiaton factor eIF3 from humans and yeast

Hershey, John W.B.; Asano, Katsura; Naranda, Tatjana; Vornlocher, Hans‐Peter; Hanachi, Parisa; Merrick, William C.

doi:10.1016/s0300-9084(97)86711-9

Cited by 65 publications

(58 citation statements)

References 17 publications

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“…The major fraction of both eIF4E and TIA-1 is found in the soluble material which does not enter the gradient, but substantial amounts of each protein cosediment with the fractions containing 40 -60S ribosomal subunits ( Figure 1, G and H, fractions 4 -6). As expected of a protein component of a particle with a mass of ϳ600,000 (Hershey et al, 1996), eIF3p110 is not found among soluble proteins at the top of the gradient (i.e., fraction 1). Roughly half of eIF3 appears in fractions 2 and 3, apparently not associated with preinitiation complexes.…”

Section: Small But Not Large Ribosomal Subunits Are Components Of Sgsmentioning

confidence: 51%

Evidence That Ternary Complex (eIF2-GTP-tRNA_i^Met)–Deficient Preinitiation Complexes Are Core Constituents of Mammalian Stress Granules

Kedersha

Chen

Gilks

et al. 2002

MBoC

544

523

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Environmental stress-induced phosphorylation of eIF2␣ inhibits protein translation by reducing the availability of eIF2-GTP-tRNA i Met, the ternary complex that joins initiator tRNA Met to the 43S preinitiation complex. The resulting untranslated mRNA is dynamically routed to discrete cytoplasmic foci known as stress granules (SGs), a process requiring the related RNA-binding proteins TIA-1 and TIAR. SGs appear to be in equilibrium with polysomes, but the nature of this relationship is obscure. We now show that most components of the 48S preinitiation complex (i.e., small, but not large, ribosomal subunits, eIF3, eIF4E, eIF4G) are coordinately recruited to SGs in arsenite-stressed cells. In contrast, eIF2 is not a component of newly assembled SGs. Cells expressing a phosphomimetic mutant (S51D) of eIF2␣ assemble SGs of similar composition, confirming that the recruitment of these factors is a direct consequence of blocked translational initiation and not due to other effects of arsenite. Surprisingly, phospho-eIF2␣ is recruited to SGs that are disassembling in cells recovering from arsenite-induced stress. We discuss these results in the context of a translational checkpoint model wherein TIA and eIF2 are functional antagonists of translational initiation, and in which lack of ternary complex drives SG assembly.

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Section: Small But Not Large Ribosomal Subunits Are Components Of Sgsmentioning

confidence: 51%

Evidence That Ternary Complex (eIF2-GTP-tRNA_i^Met)–Deficient Preinitiation Complexes Are Core Constituents of Mammalian Stress Granules

Kedersha

Chen

Gilks

et al. 2002

MBoC

544

523

View full text Add to dashboard Cite

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“…53 The EIF3S3 gene encodes the p40 subunit of eukaryotic translation initiation factor 3. 54 In Addition, the PRL-3 gene has recently been demonstrated to be associated with metastasis of colorectal cancer. 55 Unfortunately, we were unable to detect any correlation between these changes and clinicopathologic factors.…”

Section: Discussionmentioning

confidence: 99%

Genetic alterations in 102 primary gastric cancers by comparative genomic hybridization: gain of 20q and loss of 18q are associated with tumor progression

et al. 2004

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Gastric cancer is one of the most common cancers. Molecular events in the carcinogenesis of gastric cancer remain, however, largely undefined. We investigated changes in DNA copy number in 102 gastric cancers by CGH. We found changes in DNA copy number in all cases, with frequent (^30% of patients) gains at 20q, 8q, 20p, 7q, 17q, 5p, and 13q. Frequent (^20%) losses were found at 19p, 18q, 5q, 21q, 4p, 4q, 15q, and 17p. The mean number of total alterations was significantly lower in grade 3 and scirrhous-type carcinomas (10.81 in grade 3 vs 13.98 in grade 1 and grade 2, 9.31 in scirrhous-type vs 13.18 in medullary-and intermediate-type). The mean number of losses and total alterations were higher in tumors at pT2, pT3 and pT4 (4.68 and 12.77 in pT2, pT3, and pT4 vs 2.55 and 9.22 in pT1). The mean number of losses was higher in carcinomas with lymph node metastasis (4.83). The mean number of gains and total alterations were higher in carcinomas with venous invasion (8.44 and 13.28). Several chromosomal alterations were linked in a statistically significant manner to specific clinicopathological parameters. Gain of 17q, 20p, and 20q and loss of 4p were associated with the pattern of the cancer-stroma relationship; loss of 18q was associated with pT category; gain of 5p was associated with pN category; loss of 4q and loss of 21q were associated with lymphatic invasion; gain of 7p and loss of 4q and 18q were associated with venous invasion; and loss of 18q was associated with pathological stage. These data suggest that gain of 20q and loss of 18q might play an important role in the development and progression of gastric cancer. Moreover, some genes on 20q and 18q might be target genes of gastric cancer.

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“…In this location, IF3 and its eukaryotic counterpart seem to perform their anti-association activity by affecting the conformational mobility of the small ribosomal subunit: in particular, suppressing the conformational mobility of the platform, essential for association of the two ribosomal subunits. Some aspects of the initiation process of protein biosynthesis were different in eukaryotic and prokaryotic systems (31). Nevertheless, neither indicate different locations of IF3.…”

Section: Conformational Mobility Governs Subunit Association and Dissmentioning

confidence: 95%

The Search and Its Outcome: High-Resolution Structures of Ribosomal Particles from Mesophilic, Thermophilic, and Halophilic Bacteria at Various Functional States

Yonath

2002

Annu. Rev. Biophys. Biomol. Struct.

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We determined the high-resolution structures of large and small ribosomal subunits from mesophilic and thermophilic bacteria and compared them with those of the thermophilic ribosome and the halophilic large subunit. We confirmed that the elements involved in intersubunit contacts and in substrate binding are inherently flexible and that a common ribosomal strategy is to utilize this conformational variability for optimizing its functional efficiency and minimizing nonproductive interactions. Under close-to-physiological conditions, these elements maintain well-ordered characteristic conformations. In unbound subunits, the features creating intersubunit bridges within associated ribosomes lie on the interface surface, and the features that bind factors and substrates reach toward the binding site only when conditions are ripe. 257 Annu. Rev. Biophys. Biomol. Struct. 2002.31:257-273. Downloaded from www.annualreviews.org Access provided by 54.191.190.102 on 05/12/18. For personal use only. 258 YONATH INTRODUCTIONRibosomes are the universal cellular organelles that catalyze the sequential polymerization of amino acids according to the genetic blueprint encoded in the mRNA. They are built of two subunits that associate for performing this task. The larger subunit creates the peptide bonds and provides the path for the progression of the nascent proteins. The smaller subunit has key roles in the initiation of the process, in decoding the genetic message, in discriminating against non-and near-cognate aminoacylated tRNA molecules, in controlling the fidelity of codon-anti-codon interactions, and in mRNA/tRNA translocation. The prokaryotic large ribosomal subunit (50S) has a molecular weight of 1.5 × 10 6 Dalton and contains two RNA chains with a total of ∼3000 nucleotides and ∼35 proteins. The small ribosomal subunit (called 30S) has a molecular weight of 8.5 × 10 5 Dalton and contains one RNA chain of over 1500 nucleotides and ∼20 proteins.Over two decades ago, we initialized a long and demanding search for the determination of the three-dimensional structure of the ribosome by X-ray crystallography (74). The key to high-resolution data was to crystallize homogenous preparations under conditions similar to their in situ environments or to induce a selected conformation after the crystals were formed. Relatively robust ribosomal particles were chosen, assuming that they would deteriorate less during preparation and therefore provide more homogenous starting materials for crystallization.The first crystals to yield some crystallographic information (e.g., symmetry, unit cell parameters, and resolution) were of the large subunit from Bacillus stearothermophilus (71) and Haloarcula marismortui (H50S) (39,66). Shortly afterward, we characterized crystals of the small subunit from Thermus thermophilus (T30S) (72). Microcrystals of the same source were grown independently at approximately the same time (64).An alternative approach was to design complexes containing ribosomes at defined functional stages, such as o...

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Conservation and diversity in the structure of translation initiaton factor eIF3 from humans and yeast

Cited by 65 publications

References 17 publications

Evidence That Ternary Complex (eIF2-GTP-tRNA_i^Met)–Deficient Preinitiation Complexes Are Core Constituents of Mammalian Stress Granules

Evidence That Ternary Complex (eIF2-GTP-tRNA_i^Met)–Deficient Preinitiation Complexes Are Core Constituents of Mammalian Stress Granules

Genetic alterations in 102 primary gastric cancers by comparative genomic hybridization: gain of 20q and loss of 18q are associated with tumor progression

The Search and Its Outcome: High-Resolution Structures of Ribosomal Particles from Mesophilic, Thermophilic, and Halophilic Bacteria at Various Functional States

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Conservation and diversity in the structure of translation initiaton factor eIF3 from humans and yeast

Cited by 65 publications

References 17 publications

Evidence That Ternary Complex (eIF2-GTP-tRNAiMet)–Deficient Preinitiation Complexes Are Core Constituents of Mammalian Stress Granules

Evidence That Ternary Complex (eIF2-GTP-tRNAiMet)–Deficient Preinitiation Complexes Are Core Constituents of Mammalian Stress Granules

Genetic alterations in 102 primary gastric cancers by comparative genomic hybridization: gain of 20q and loss of 18q are associated with tumor progression

The Search and Its Outcome: High-Resolution Structures of Ribosomal Particles from Mesophilic, Thermophilic, and Halophilic Bacteria at Various Functional States

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Product

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Evidence That Ternary Complex (eIF2-GTP-tRNA_i^Met)–Deficient Preinitiation Complexes Are Core Constituents of Mammalian Stress Granules

Evidence That Ternary Complex (eIF2-GTP-tRNA_i^Met)–Deficient Preinitiation Complexes Are Core Constituents of Mammalian Stress Granules