Translation Initiation Requires Cell Division Cycle 123 (Cdc123) to Facilitate Biogenesis of the Eukaryotic Initiation Factor 2 (eIF2)

Perzlmaier, Angelika F.; Richter, Frank; Seufert, Wolfgang

doi:10.1074/jbc.m113.472290

Cited by 31 publications

(52 citation statements)

References 44 publications

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“…Based on structural studies of the archaeal and yeast complexes, eIF2g is the keystone of the eIF2 complex with separate docking sites for the eIF2a and eIF2b subunits (Schmitt et al 2012;Hussain et al 2014;Llacer et al 2015). The incorporation of eIF2g in the eIF2 complex is dependent on the apparently eIF2-specific chaperone Cdc123 (Perzlmaier et al 2013). The amino acid sequence and structure of eIF2g and aIF2g show striking similarity to elongation factor EF-Tu from bacteria (Hannig et al 1993;Schmitt et al 2002;Roll-Mecak et al 2004).…”

Section: Ternary Complex Formationmentioning

confidence: 99%

Mechanism and Regulation of Protein Synthesis in Saccharomyces cerevisiae

2016

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In this review, we provide an overview of protein synthesis in the yeast Saccharomyces cerevisiae. The mechanism of protein synthesis is well conserved between yeast and other eukaryotes, and molecular genetic studies in budding yeast have provided critical insights into the fundamental process of translation as well as its regulation. The review focuses on the initiation and elongation phases of protein synthesis with descriptions of the roles of translation initiation and elongation factors that assist the ribosome in binding the messenger RNA (mRNA), selecting the start codon, and synthesizing the polypeptide. We also examine mechanisms of translational control highlighting the mRNA cap-binding proteins and the regulation of GCN4 and CPA1 mRNAs.

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Section: Ternary Complex Formationmentioning

confidence: 99%

Mechanism and Regulation of Protein Synthesis in Saccharomyces cerevisiae

2016

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“…In vivo assembly of the eIF2 complex was shown to depend on Cdc123. Sc-Cdc123 activity involved an interaction with the unassembled eIF2γ subunit (Perzlmaier et al, 2013). eIF2γ is made of three domains: the GTP-binding domain, γDI, and the two β-barrels γDII and γDIII (Schmitt et al, 2010).…”

Section: Binding Of Cdc123 To Eif2γmentioning

confidence: 99%

“…eIF2γ is made of three domains: the GTP-binding domain, γDI, and the two β-barrels γDII and γDIII (Schmitt et al, 2010). Within eIF2γ, domain III was shown to be sufficient for binding to Cdc123 (Perzlmaier et al, 2013).…”

Section: Binding Of Cdc123 To Eif2γmentioning

confidence: 99%

“…Previous results had suggested that within domain III, the C-terminal tail, specific of eukaryotic eIF2γ was required for the interaction with Cdc123. Indeed, removal of thirteen amino acids at the C-terminal extremity of eIF2γ (residues 515 to 527) was sufficient to render the protein non-functional in the binding to Cdc123 or to eIF2α and eIF2β subunits (Perzlmaier et al, 2013). On the contrary, the removal of 4 amino acids from the C-terminus was tolerated, since binding to Cdc123 and assembly with α and γ subunit still occurred (Perzlmaier et al, 2013).…”

Section: Binding Of Cdc123 To Eif2γmentioning

confidence: 99%

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Cdc123, a Cell Cycle Regulator Needed for eIF2 Assembly, Is an ATP-Grasp Protein with Unique Features

et al. 2015

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Eukaryotic initiation factor 2 (eIF2), a heterotrimeric guanosine triphosphatase, has a central role in protein biosynthesis by supplying methionylated initiator tRNA to the ribosomal translation initiation complex and by serving as a target for translational control in response to stress. Recent work identified a novel step indispensable for eIF2 function: assembly of eIF2 from its three subunits by the cell proliferation protein Cdc123. We report the first crystal structure of a Cdc123 representative, that from Schizosaccharomyces pombe, both isolated and bound to domain III of Saccharomyces cerevisiae eIF2γ. The structures show that Cdc123 resembles enzymes of the ATP-grasp family. Indeed, Cdc123 binds ATP-Mg(2+), and conserved residues contacting ATP-Mg(2+) are essential for Cdc123 to support eIF2 assembly and cell viability. A docking of eIF2αγ onto Cdc123, combined with genetic and biochemical experiments, allows us to propose a model explaining how Cdc123 participates in the biogenesis of eIF2 through facilitating assembly of eIF2γ to eIF2α.

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“…P2RY14 (Supplemental Spreadsheet 1), a purinergic receptor for UDP-glucose and other UDP-sugars is an asthma risk gene (52) . Finally, CDC123 (Supplemental Spreadsheet 1) is critical for the eukaryotic translation initiation factor 2 (eIF2) activity, which is required for the onset of protein synthesis (53) . Conversely, EEF2K, a kinase inhibitor of protein translation elongation (54) was one of the top 30 proteins down-regulated by IL-3 (Supplemental Spreadsheet 1).…”

Section: Resultsmentioning

confidence: 99%

Proteomic and Phosphoproteomic Changes Induced by Prolonged Activation of Human Eosinophils with IL-3

et al. 2018

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Purified human eosinophils treated for 18-24 h with IL-3 adopt a unique activated phenotype marked by increased reactivity to aggregated immunoglobulin-G (IgG). To characterize this phenotype, we quantified protein abundance and phosphorylation by multi-plexed isobaric labeling combined with high-resolution mass spectrometry. Purified blood eosinophils of five individuals were treated with IL-3 or no cytokine for 20 hours, and comparative data were obtained on abundance of 5385 proteins and phosphorylation at 7330 sites. The 1150 proteins that were significantly up-regulated (q<0.05, pair-wise t test with Benjamini-Hoachberg correction) by IL-3 included the IL3RA and CSF2RB subunits of the IL-3 receptor, the low-affinity receptor for IgG (FCGR2B), 96 proteins involved in protein translation, and 55 proteins involved in cytoskeleton organization. Among the 703 proteins that decreased were 78 mitochondrial proteins. Dynamic regulation of protein phosphorylation was detected at 4218 sites. These included multiple serines in CSF2RB; Y694 of STAT5, a key site of activating phosphorylation downstream of IL3RA/CSF2RB; and multiple sites in RPS6KA1, RPS6, and EIF4B, which are responsible for translational initiation. We conclude that IL-3 up-regulates overall protein synthesis and targets specific proteins for up-regulation, including its own receptor.

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Translation Initiation Requires Cell Division Cycle 123 (Cdc123) to Facilitate Biogenesis of the Eukaryotic Initiation Factor 2 (eIF2)

Cited by 31 publications

References 44 publications

Mechanism and Regulation of Protein Synthesis in Saccharomyces cerevisiae

Mechanism and Regulation of Protein Synthesis in Saccharomyces cerevisiae

Cdc123, a Cell Cycle Regulator Needed for eIF2 Assembly, Is an ATP-Grasp Protein with Unique Features

Proteomic and Phosphoproteomic Changes Induced by Prolonged Activation of Human Eosinophils with IL-3

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