Initiation of protein synthesis in mammalian cells

Pain, Virginia M.

doi:10.1042/bj2350625

Cited by 361 publications

(163 citation statements)

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“…There is good correspondence between the experimentally determined M, values of the eIF-2B in yeast and mammals (Pain, 1986), and, in addition, the human homolog of CCD6 (eIF-2Bt) has recently been cloned and sequenced (Bushman et al, 1993a). Thus, it is thought that eIF-2B is conserved throughout the evolution of eukaryotes (Cigan et al, 1993).…”

mentioning

confidence: 83%

Multidomain organization of eukaryotic guanine nucleotide exchange translation initiation factor eIF‐2B subunits revealed by analysis of conserved sequence motifs

Koonin

1995

Protein Science

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Computer-assisted analysis of amino acid sequences using methods for database screening with individual sequences and with multiple alignment blocks reveals a complex multidomain organization of yeast proteins CCD6 and CCD1 , and mammalian homolog of CCD6 -subunits of the eukaryotic translation initiation factor eIF-2B involved in GDP/GTP exchange on eIF-2. It is shown that these proteins contain a putative nucleotide-binding domain related to a variety of nucleotidyltransferases, most of which are involved in nucleoside diphosphate-sugar formation in bacteria. Three conserved motifs, one of which appears to be a variant of the phosphate-binding site (P-loop) and another that may be considered a specific version of the Mg2+-binding site of NTP-utilizing enzymes, were identified in the nucleotidyltransferase-related domain. Together with the third unique motif adjacent to the P-loop, these motifs comprise the signature of a new superfamily of nucleotide-binding domains. A domain consisting of hexapeptide amino acid repeats with a periodic distribution of bulky hydrophobic residues (isoleucine patch), which previously have been identified in bacterial acetyltransferases, is located toward the C-terminus from the nucleotidyltransferase-related domain. Finally, at the very C-termini of GCD6, ~I F -~B E , and two other eukaryotic translation initiation factors, eIF-4-y and eIF-5, there is a previously undetected, conserved domain. It is hypothesized that the nucleotidyltransferase-related domain is directly involved in the GDPIGTP exchange, whereas the C-terminal conserved domain may be involved in the interaction of eIF-2B, eIF-47, and eIF-5 with eIF-2.

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confidence: 83%

Multidomain organization of eukaryotic guanine nucleotide exchange translation initiation factor eIF‐2B subunits revealed by analysis of conserved sequence motifs

Koonin

1995

Protein Science

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“…The relative amounts of the ␣-subunit of eIF-2 (eIF-2␣), the phosphorylated form of eIF-2␣, and the ⑀-subunit of eIF-2B (eIF2-B⑀) in gastrocnemius and heart were estimated by protein immunoblot analysis, as described previously (30,32,54). eIF-2 and eIF-2B were chosen because change in the content and/or activity of these initiation factors correlates with alterations in protein synthesis (10,42). eIF-2 consists of three subunits of which the ␣-subunit appears important in regulating protein synthesis (42).…”

Section: Methodsmentioning

confidence: 99%

“…Translation initiation is regulated by a large number of protein factors termed eukaryotic initiation factors (eIFs). One of these initiation factors, eIF-2, mediates the first step in initiation and promotes the attachment of the initiator methionyl-tRNA (met-tRNA i ) to the 40S ribosomal subunit to form the 43S preinitiation complex (10,42). A second critical point of translational regulation involves the binding of the 5Ј-end of cellular mRNA to the 43S preinitiation complex, which is mediated by the cap-binding protein complex eIF-4F (42,44).…”

mentioning

confidence: 99%

“…One of these initiation factors, eIF-2, mediates the first step in initiation and promotes the attachment of the initiator methionyl-tRNA (met-tRNA i ) to the 40S ribosomal subunit to form the 43S preinitiation complex (10,42). A second critical point of translational regulation involves the binding of the 5Ј-end of cellular mRNA to the 43S preinitiation complex, which is mediated by the cap-binding protein complex eIF-4F (42,44). Although the decrease in muscle protein synthesis in various catabolic conditions has been generally linked to inhibition of peptide-chain initiation, the exact site of the molecular lesion often varies (10,31,44).…”

mentioning

confidence: 99%

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TNF-α impairs heart and skeletal muscle protein synthesis by altering translation initiation

Lang

Frost

Nairn

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

231

229

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This study examined potential mechanisms contributing to the inhibition of protein synthesis in skeletal muscle and heart after administration of tumor necrosis factor (TNF)-α. Rats had vascular catheters implanted, and TNF-α was infused continuously for 24 h. TNF-α decreased in vivo-determined rates of global protein synthesis in gastrocnemius (39%) and heart (25%). The TNF-α-induced decrease in protein synthesis in the gastrocnemius involved a reduction in the synthesis of both myofibrillar and sarcoplasmic proteins. To identify potential mechanisms responsible for regulating mRNA translation, we examined several eukaryotic initiation factors (eIFs) and elongation factors (eEFs). TNF-α decreased the activity of eIF-2B in muscle (39%) but not in heart. This diminished activity was not caused by a reduction in the content of eIF-2Bε or the content and phosphorylation state of eIF-2α. Skeletal muscle and heart from TNF-α-treated rats demonstrated 1) an increased binding of the translation repressor 4E-binding protein-1 (4E-BP1) with eIF-4E, 2) a decreased amount of eIF-4E associated with eIF-4G, and 3) a decreased content of the hyperphosphorylated γ-form of 4E-BP1. In contrast, the infusion of TNF-α did not alter the content of eEF-1α or eEF-2, or the phosphorylation state of eEF-2. In summary, these data suggest that TNF-α impairs skeletal muscle and heart protein synthesis, at least in part, by decreasing mRNA translational efficiency resulting from an impairment in translation initiation associated with alterations in eIF-4E availability.

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“…This compares with a 62-65% amino acid identity observed between the TIF1I/TIF2 and eIF4AI/II, which are proteins known to recognize mRNA cap structure, bind mRNA to ribosomes and catalyze RNA unwinding (25,26). A more striking homology was found between p54 and the recently reported Drosophila oocyte-specific ME31B gene.…”

Section: Transcription Of P54 Gene In Various Human Tissuesmentioning

confidence: 73%

Cloning, expression and localization of an RNA helicase gene from a human lymphoid cell line with chromosomal breakpoint 11q23.3

Lü

Yunis

1992

Nucl Acids Res

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A gene encoding a putative human RNA helicase, p54, has been cloned and mapped to the band q23.3 of chromosome 11. The predicted amino acid sequence shares a striking homology (75% identical) with the female germline-specific RNA helicase ME31B gene of Drosophila. Unlike ME31B, however, the new gene expresses an abundant transcript in a large number of adult tissues and its 5' non-coding region was found split in a t(11;14)(q23.3;q32.3) cell line from a diffuse large B-cell lymphoma.

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Initiation of protein synthesis in mammalian cells

Cited by 361 publications

References 155 publications

Multidomain organization of eukaryotic guanine nucleotide exchange translation initiation factor eIF‐2B subunits revealed by analysis of conserved sequence motifs

Multidomain organization of eukaryotic guanine nucleotide exchange translation initiation factor eIF‐2B subunits revealed by analysis of conserved sequence motifs

TNF-α impairs heart and skeletal muscle protein synthesis by altering translation initiation

Cloning, expression and localization of an RNA helicase gene from a human lymphoid cell line with chromosomal breakpoint 11q23.3

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