Translation Elongation Factor 1 Functions in the Yeast Saccharomyces cerevisiae

Anand, Monika; Valente, Louis; Carr-Schmid, Anne; Munshi, Raj; Olarewaju, Olubunmi; Ortiz, Pedro A.; Kinzy, Terri Goss

doi:10.1101/sqb.2001.66.439

Cited by 14 publications

(17 citation statements)

References 12 publications

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“…The crystal structure of the EF-Tu:GDPNP:Phe-tRNA Phe complex reveals aa-tRNA binding to EF-Tu requires only minor parts of both domain II and tRNA to sustain stable contacts (12). That eEF1A employs the same aa-tRNA binding site is supported by genetic and biochemical data (13)(14)(15). Interestingly, eEF1B␣ contacts many domain II eEF1A residues in the region hypothesized to be involved in the binding of the aatRNA CCA end (8).…”

mentioning

confidence: 93%

Coordination of Eukaryotic Translation Elongation Factor 1A (eEF1A) Function in Actin Organization and Translation Elongation by the Guanine Nucleotide Exchange Factor eEF1Bα

Pittman¹,

Kandl

Lewis³

et al. 2009

Journal of Biological Chemistry

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Eukaryotic translation elongation factor 1A (eEF1A) both shuttles aminoacyl-tRNA (aa-tRNA) to the ribosome and binds and bundles actin. A single domain of eEF1A is proposed to bind actin, aa-tRNA and the guanine nucleotide exchange factor eEF1B␣. We show that eEF1B␣ has the ability to disrupt eEF1A-induced actin organization. Mutational analysis of eEF1B␣ F163, which binds in this domain, demonstrates effects on growth, eEF1A binding, nucleotide exchange activity, and cell morphology. These phenotypes can be partially restored by an intragenic W130A mutation. Furthermore, the combination of F163A with the lethal K205A mutation restores viability by drastically reducing eEF1B␣ affinity for eEF1A. This also results in a consistent increase in actin bundling and partially corrected morphology. The consequences of the overlapping functions in this eEF1A domain and its unique differences from the bacterial homologs provide a novel function for eEF1B␣ to balance the dual roles in actin bundling and protein synthesis.

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confidence: 93%

Coordination of Eukaryotic Translation Elongation Factor 1A (eEF1A) Function in Actin Organization and Translation Elongation by the Guanine Nucleotide Exchange Factor eEF1Bα

Pittman¹,

Kandl

Lewis³

et al. 2009

Journal of Biological Chemistry

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“…While these include both catalytic and regulatory proteins, the C-terminal amino acids 544-704 of the eIF2Be subunit define the minimal catalytic region of the GEF in vitro and in vivo (Gomez et al 2002). The GEF for Saccharomyces cerevisiae eEF1A, eEF1B, is composed of two subunits (Anand et al 2001). The eEF1Ba subunit (formerly EF-1b) is catalytic whereas the eEF1Bg (formerly EF-1g) subunit appears to regulate the activity of eEF1Ba.…”

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confidence: 99%

Unique Classes of Mutations in the Saccharomyces cerevisiae G-Protein Translation Elongation Factor 1A Suppress the Requirement for Guanine Nucleotide Exchange

et al. 2006

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G-proteins play critical roles in many cellular processes and are regulated by accessory proteins that modulate the nucleotide-bound state. Such proteins, including eukaryotic translation elongation factor 1A (eEF1A), are frequently reactivated by guanine nucleotide exchange factors (GEFs). In the yeast Saccharomyces cerevisiae, only the catalytic subunit of the GEF complex, eEF1Ba, is essential for viability. The requirement for the TEF5 gene encoding eEF1Ba can be suppressed by the presence of excess substrate, eEF1A. These cells, however, have defects in growth and translation. Two independent unbiased screens performed to dissect the cause of these phenotypes yielded dominant suppressors that bypass the requirement for extra eEF1A. Surprisingly, all mutations are in the G-protein eEF1A and cluster in its GTP-binding domain. Five mutants were used to construct novel strains expressing only the eEF1A mutant at normal levels. These strains show no growth defects and little to no decreases in total translation, which raises questions as to the evolutionary expression of GEF complexity and other potential functions of this complex. The location of the mutations on the eEF1A-eEF1Ba structure suggests that their mechanism of suppression may depend on effects on the conserved G-protein elements: the P-loop and NKXD nucleotide-binding element.

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“…Recent studies showed that rad23D rpn10D is also extremely sensitive to inhibitors of protein synthesis (Chuang et al 2005), suggesting that Rad23 and Rpn10 perform an important role in the degradation of nascent, misfolded proteins. A genetic search for dosage (high-copy) suppressors yielded TEF1 (Chuang et al 2005), a gene encoding the translation elongation factor eEF1A (Anand et al 2001). We proposed that eEF1A provided a link between protein synthesis and protein degradation by promoting the transfer of nascent, damaged proteins to the proteasome (Chuang et al 2005).…”

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confidence: 99%

Saccharomyces cerevisiae Ub-Conjugating Enzyme Ubc4 Binds the Proteasome in the Presence of Translationally Damaged Proteins

Chuang

Madura

2005

Genetics

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Surveillance mechanisms that monitor protein synthesis can promote rapid elimination of misfolded nascent proteins. We showed that the translation elongation factor eEF1A and the proteasome subunit Rpt1 play a central role in the translocation of nascent-damaged proteins to the proteasome. We show here that multiubiquitinated proteins, and the ubiquitin-conjugating (E2) enzyme Ubc4, are rapidly detected in the proteasome following translational damage. However, Ubc4 levels in the proteasome were reduced significantly in a strain that expressed a mutant Rpt1 subunit. Ubc4 and Ubc5 are functionally redundant E2 enzymes that represent ideal candidates for ubiquitinating damaged nascent proteins because they lack significant substrate specificity, are required for the degradation of bulk, damaged proteins, and contribute to cellular stress-tolerance mechanisms. In agreement with this hypothesis, we determined that ubc4D ubc5D is exceedingly sensitive to protein translation inhibitors. Collectively, these studies suggest a specific role for Ubc4 and Ubc5 in the degradation of cotranslationally damaged proteins that are targeted to the proteasome.

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Translation Elongation Factor 1 Functions in the Yeast Saccharomyces cerevisiae

Cited by 14 publications

References 12 publications

Coordination of Eukaryotic Translation Elongation Factor 1A (eEF1A) Function in Actin Organization and Translation Elongation by the Guanine Nucleotide Exchange Factor eEF1Bα

Coordination of Eukaryotic Translation Elongation Factor 1A (eEF1A) Function in Actin Organization and Translation Elongation by the Guanine Nucleotide Exchange Factor eEF1Bα

Unique Classes of Mutations in the Saccharomyces cerevisiae G-Protein Translation Elongation Factor 1A Suppress the Requirement for Guanine Nucleotide Exchange

Saccharomyces cerevisiae Ub-Conjugating Enzyme Ubc4 Binds the Proteasome in the Presence of Translationally Damaged Proteins

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