Initiation of eukaryotic protein synthesis

Thomas, A.A.M; Benne, Rob; Voorma, Harry O.

doi:10.1016/0014-5793(81)80076-2

Cited by 58 publications

(10 citation statements)

References 107 publications

(28 reference statements)

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“…Rather, its activity in cell-free systems is limited to stimulating the formation of ApUpGp-dependent methionylpuromycin and the enhancement of poly(U)-dependent polyphenylalanine synthesis (5,6). At the present time, no function in intact cells has been identified, and the reality of a physiological role for this factor has been questioned (5, 6).…”

Section: Methodsmentioning

confidence: 99%

“…Of all the translation initiation factors, eIF-4D remains the most problematical, since no definite role has been determined for it in protein synthesis with natural messengers (5,6). Rather, its activity in cell-free systems is limited to stimulating the formation of ApUpGp-dependent methionylpuromycin and the enhancement of poly(U)-dependent polyphenylalanine synthesis (5,6).…”

Section: Methodsmentioning

confidence: 99%

“…Hypusine has thus far been shown to occur naturally as a post-translational modification in only one protein, which we have termed Hy' (Mr, 17,(0)(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)000; pI, =5. 1), in growing lymphocytes and fibroblasts of human and animal origin (2-4).…”

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confidence: 99%

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Identification of the hypusine-containing protein hy+ as translation initiation factor eIF-4D.

Cooper¹,

Park²,

Folk³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

193

109

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A single protein of Mr 17,000-19,000 and pI "-5. 1, found in all animal cells we have studied to date, undergoes posttranslational modification in growing cells to form the unusual amino acid hypusine. Because of the association of this modification with the increasing rate of protein synthesis during lymphocyte growth stimulation, its subcellular distribution, and its widespread occurrence and structural conservation among animal cells, we considered the possibility that this protein might be a translation initiation factor. Purified rabbit reticulocyte factors (eukaryote initiation factors) eIF4C and eIF-4D were chosen for study because of their Mr (17,000-19,000) and acidic pl. The hypusinecontaining protein and purified eIF-4D showed identity of electrophoretic mobility in both isoelectric focusing and NaDodSO4/ polyacrylamide gel electrophoresis dimensions, while eIF-4C was clearly nonidentical. Purified eIF-4D contained approximately 1 mol of hypusine per mol of protein. Since only one protein has thus far been observed to contain hypusine, we conclude that eIF-4D is the hypusine-containing protein. On the basis of relative synthesis among lymphocyte proteins and detection by Coomassie blue staining, we also conclude that eIF-4D is a major cell protein.It is possible that the activity of this factor is modulated by posttranslational hypusine formation, which may play a role in regulation of protein synthesis during lymphocyte growth stimulation.Hypusine [N6-(4-amino-2-hydroxybutyl)lysine] is an unusual amino acid (1) formed by the addition of a butylamino group, derived from spermidine, to the side chain of a lysine residue in a peptide chain followed by hydroxylation at carbon 2 of the added group (2, 3). Hypusine has thus far been shown to occur naturally as a post-translational modification in only one protein, which we have termed Hy' (Mr, 17,(0)(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)000; pI, =5. 1), in growing lymphocytes and fibroblasts of human and animal origin (2-4). This protein is probably formed in all growing eukaryotic cells. In quiescent lymphocytes and serum-deprived fibroblasts, hypusine formation is minimal although the substrate protein, Hy°, is continuously synthesized. On stimulation of lymphocytes with a mitogen, the conversion of Hy°to Hy' increases detectably within a few hours. The rate of hypusine formation increases in parallel with the increasing rate of protein synthesis characteristic of activated lymphocytes (4). Thus, the production of Hy' is one of the relatively early events characterizing the activation of quiescent lymphocytes.Hy from human lymphocytes and Chinese hamster ovary fibroblasts showed identical electrophoretic mobility in both electrofocusing and NaDodSO4/polyacrylamide gel electrophoresis dimensions (4), indicating a widely distributed protein with well-conserved structure. Our preliminary observations showed that the great bulk of Hy' was found free in the cytosol but that small amounts were found in ribosomal and cytosk...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Identification of the hypusine-containing protein hy+ as translation initiation factor eIF-4D.

Cooper¹,

Park²,

Folk³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

193

109

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“…The phosphorylation ofArtemia eEF 1Ba Ser-89 by casein kinase II inhibits its ability to catalyze guaninenucleotide exchange activity on eEF 1A [136]. In addition, phosphorylation of Ser-89 inhibits the formation of an Artemia eEF1AB complex [318]. Conspicuously missing in the rice and wheat eEFIBa sequence is a counterpart to Ser-89 of Artemia eEF1Ba.…”

Section: P Anserinamentioning

confidence: 99%

The plant translational apparatus

1996

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“…eIF1A is a small protein (17)(18)(19)(20)(21)(22) kDa) that appears to undergo no post-translational modification reactions (7). The initiation factor is implicated in 80 S ribosome dissociation, stabilizes initiator Met-tRNA i binding to 40 S ribosomal subunits, and facilitates mRNA binding to the 40 S preinitiation complex (2,8). Thus, eIF1A has pleiotropic effects at different steps of the initiation pathway.…”

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confidence: 99%

Characterization of Yeast Translation Initiation Factor 1A and Cloning of Its Essential Gene

Wei

Kainuma

Hershey

1995

Journal of Biological Chemistry

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Translation initiation factor eIF1A is required in vitro for maximal rates of protein synthesis in mammalian systems. It functions primarily by dissociating ribosomes and stabilizing 40 S preinitiation complexes. To better elucidate its precise role in promoting the translation initiation process, the yeast form of eIF1A has been identified in Saccharomyces cerevisiae and purified to homogenity on the basis of its cross-reaction with antibodies prepared against mammalian eIF1A. The apparent mass of yeast eIF1A (22 kDa) resembles that of the mammalian homolog (20 kDa), and the yeast factor is active in stimulating methionyl-puromycin synthesis in an assay composed of mammalian components. The gene encoding yeast eIF1A, named TIF11, was cloned and shown to be single copy. TIF11 encodes a protein comprising 153 amino acids (17.4 kDa); the deduced amino acid sequence exhibits 65% identity with the sequence of human eIF1A. Both human and yeast eIF1A contain clusters of positive residues at the N terminus and negative residues at the C terminus. Deletion/disruption of TIF11 demonstrates that eIF1A is essential for cell growth. Expression of human eIF1A cDNA rescues the growth defect of TIF11-disrupted cells, indicating that the structure/function of yeast and mammalian eIF1A is highly conserved.The initiation phase of protein synthesis in eukaryotic cells is promoted by a large number of proteins called initiation factors (eIF) 1 (for reviews, see Refs. 1 and 2). One of these, eIF1A (formerly eIF-4C), has been purified from both mammalian (3-5) and plant cells (6) and is essential for maximal in vitro protein synthesis. eIF1A is a small protein (17-22 kDa) that appears to undergo no post-translational modification reactions (7). The initiation factor is implicated in 80 S ribosome dissociation, stabilizes initiator Met-tRNA i binding to 40 S ribosomal subunits, and facilitates mRNA binding to the 40 S preinitiation complex (2, 8). Thus, eIF1A has pleiotropic effects at different steps of the initiation pathway. Purified eIF1A from wheat germ and rabbit reticulocytes functions interchangeably in vitro (6), suggesting that the functional domains are highly conserved. Nevertheless, a clear understanding of how eIF1A promotes the initiation phase of protein synthesis is lacking.The process of translation initiation appears to be very conserved between eukaryotes as distantly related as mammals and the yeast, Saccharomyces cerevisiae. This conclusion is based on similarities of mRNA structure and the basic mechanism of protein synthesis (9). Particularly striking are the structural similarities between yeast and mammalian initiation factors, which share amino acid sequence identities ranging from 26 to 71%. This strong conservation has made it possible to recognize several yeast genes as encoding specific initiation factors based on their sequence homology to mammalian cDNAs: eIF2␣ (10), eIF2␤ (11), eIF2␥ (12), eIF2B⑀ (13), eIF4A (14), eIF4B (15, 16), eIF4␣ (17), eIF4␥ (18), eIF5 (19), and eIF5A (20). In addition, there ar...

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Initiation of eukaryotic protein synthesis

Cited by 58 publications

References 107 publications

Identification of the hypusine-containing protein hy+ as translation initiation factor eIF-4D.

Identification of the hypusine-containing protein hy+ as translation initiation factor eIF-4D.

The plant translational apparatus

Characterization of Yeast Translation Initiation Factor 1A and Cloning of Its Essential Gene

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