GCN2

Summary

Gene Symbol: GCN2
Description: serine/threonine-protein kinase GCN2
Alias: AAS1, AAS102, NDR2, serine/threonine-protein kinase GCN2
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Wek R, Ramirez M, Jackson B, Hinnebusch A. Identification of positive-acting domains in GCN2 protein kinase required for translational activation of GCN4 expression. Mol Cell Biol. 1990;10:2820-31 pubmed
    GCN4 is a transcriptional activator of amino acid-biosynthetic genes in the yeast Saccharomyces cerevisiae. GCN2, a translational activator of GCN4 expression, contains a domain homologous to the catalytic subunit of eucaryotic protein ..
  2. Diallinas G, Thireos G. Genetic and biochemical evidence for yeast GCN2 protein kinase polymerization. Gene. 1994;143:21-7 pubmed
    The GCN2 (general control kinase 2) protein is an eIF2-alpha (eukaryotic initiation factor alpha) kinase which mediates translational derepression of the yeast general control transcriptional activator, GCN4, upon amino-acid starvation...
  3. Ramirez M, Wek R, Hinnebusch A. Ribosome association of GCN2 protein kinase, a translational activator of the GCN4 gene of Saccharomyces cerevisiae. Mol Cell Biol. 1991;11:3027-36 pubmed
    ..b>GCN2 is a protein kinase required for increased translation of GCN4 mRNA in amino acid-starved cells...
  4. Singh C, Lee B, Udagawa T, Mohammad Qureshi S, Yamamoto Y, Pavitt G, et al. An eIF5/eIF2 complex antagonizes guanine nucleotide exchange by eIF2B during translation initiation. EMBO J. 2006;25:4537-46 pubmed
    ..We propose that the eIF2/eIF5 complex represents a cytoplasmic reservoir for eIF2 that antagonizes eIF2B-promoted guanine nucleotide exchange, enabling coordinated regulation of translation initiation. ..
  5. Padyana A, Qiu H, Roll Mecak A, Hinnebusch A, Burley S. Structural basis for autoinhibition and mutational activation of eukaryotic initiation factor 2alpha protein kinase GCN2. J Biol Chem. 2005;280:29289-99 pubmed
    The GCN2 protein kinase coordinates protein synthesis with levels of amino acid stores by phosphorylating eukaryotic translation initiation factor 2...
  6. Pavitt G, Yang W, Hinnebusch A. Homologous segments in three subunits of the guanine nucleotide exchange factor eIF2B mediate translational regulation by phosphorylation of eIF2. Mol Cell Biol. 1997;17:1298-313 pubmed
    ..Most of the eIF2 is phosphorylated in certain mutants, suggesting that these substitutions allow eIF2B to accept phosphorylated eIF2 as a substrate for nucleotide exchange. ..
  7. Dever T, Feng L, Wek R, Cigan A, Donahue T, Hinnebusch A. Phosphorylation of initiation factor 2 alpha by protein kinase GCN2 mediates gene-specific translational control of GCN4 in yeast. Cell. 1992;68:585-96 pubmed
    ..phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2) by the protein kinase GCN2 mediates translational control of the yeast transcriptional activator GCN4...
  8. Lageix S, Rothenburg S, Dever T, Hinnebusch A. Enhanced interaction between pseudokinase and kinase domains in Gcn2 stimulates eIF2? phosphorylation in starved cells. PLoS Genet. 2014;10:e1004326 pubmed publisher
    The stress-activated protein kinase Gcn2 regulates protein synthesis by phosphorylation of translation initiation factor eIF2?, from yeast to mammals...
  9. Sattlegger E, Hinnebusch A. Separate domains in GCN1 for binding protein kinase GCN2 and ribosomes are required for GCN2 activation in amino acid-starved cells. EMBO J. 2000;19:6622-33 pubmed
    b>GCN2 stimulates GCN4 translation in amino acid-starved cells by phosphorylating the alpha-subunit of translation initiation factor 2. GCN2 function in vivo requires the GCN1/GCN20 complex, which binds to the N-terminal domain of GCN2...

More Information

Publications70

  1. Hinnebusch A. Gene-specific translational control of the yeast GCN4 gene by phosphorylation of eukaryotic initiation factor 2. Mol Microbiol. 1993;10:215-23 pubmed
    ..Phosphorylation of eIF-2 by the protein kinase GCN2 decreases the concentration of eIF-2.GTP...
  2. Donze O, Picard D. Hsp90 binds and regulates Gcn2, the ligand-inducible kinase of the alpha subunit of eukaryotic translation initiation factor 2 [corrected]. Mol Cell Biol. 1999;19:8422-32 pubmed
    The protein kinase Gcn2 stimulates translation of the yeast transcription factor Gcn4 upon amino acid starvation...
  3. Qiu H, Garcia Barrio M, Hinnebusch A. Dimerization by translation initiation factor 2 kinase GCN2 is mediated by interactions in the C-terminal ribosome-binding region and the protein kinase domain. Mol Cell Biol. 1998;18:2697-711 pubmed
    The protein kinase GCN2 stimulates translation of the transcriptional activator GCN4 in yeast cells starved for amino acids by phosphorylating translation initiation factor 2...
  4. Garcia Barrio M, Dong J, Ufano S, Hinnebusch A. Association of GCN1-GCN20 regulatory complex with the N-terminus of eIF2alpha kinase GCN2 is required for GCN2 activation. EMBO J. 2000;19:1887-99 pubmed
    ..mRNA translation due to phosphorylation of the alpha-subunit of initiation factor 2 (eIF2) by its specific kinase, GCN2, requires binding of uncharged tRNA to a histidyl-tRNA synthetase (HisRS)-like domain in GCN2...
  5. Menacho Márquez M, Perez Valle J, Arino J, Gadea J, Murguía J. Gcn2p regulates a G1/S cell cycle checkpoint in response to DNA damage. Cell Cycle. 2007;6:2302-5 pubmed
  6. Jiménez Díaz A, Remacha M, Ballesta J, Berlanga J. Phosphorylation of initiation factor eIF2 in response to stress conditions is mediated by acidic ribosomal P1/P2 proteins in Saccharomyces cerevisiae. PLoS ONE. 2013;8:e84219 pubmed publisher
    ..in vitro phosphorylation of the initiation factor eIF2 by stimulating the autophosphorylation and activation of GCN2 kinase. Indeed, these ribosomal proteins do not stimulate other eIF2? kinases, such as PKR and HRI...
  7. Qiu H, Hu C, Anderson J, Björk G, Sarkar S, Hopper A, et al. Defects in tRNA processing and nuclear export induce GCN4 translation independently of phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2. Mol Cell Biol. 2000;20:2505-16 pubmed
    ..binding to eukaryotic translation initiation factor 2 (eIF2) in response to eIF2 phosphorylation by protein kinase GCN2. It was shown previously that GCN4 translation could be induced independently of GCN2 by overexpressing a mutant ..
  8. Visweswaraiah J, Lee S, Hinnebusch A, Sattlegger E. Overexpression of eukaryotic translation elongation factor 3 impairs Gcn2 protein activation. J Biol Chem. 2012;287:37757-68 pubmed publisher
    In eukaryotes, phosphorylation of translation initiation factor 2? (eIF2?) by the kinase Gcn2 (general control nonderepressible 2) is a key response to amino acid starvation...
  9. Hinnebusch A, Fink G. Positive regulation in the general amino acid control of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1983;80:5374-8 pubmed
    ..Either aas1- or aas2- in combination with tra3- has the Tra- phenotype, whereas aas3- in combination with tra3- has the Aas- ..
  10. He H, Singh I, Wek S, Dey S, Baird T, Wek R, et al. Crystal structures of GCN2 protein kinase C-terminal domains suggest regulatory differences in yeast and mammals. J Biol Chem. 2014;289:15023-34 pubmed publisher
    In response to amino acid starvation, GCN2 phosphorylation of eIF2 leads to repression of general translation and initiation of gene reprogramming that facilitates adaptation to nutrient stress...
  11. Goossens A, Dever T, Pascual Ahuir A, Serrano R. The protein kinase Gcn2p mediates sodium toxicity in yeast. J Biol Chem. 2001;276:30753-60 pubmed
    ..The gcn2 phenotype was not accompanied by changes in sodium or potassium homeostasis...
  12. Dever T, Yang W, Astrom S, Byström A, Hinnebusch A. Modulation of tRNA(iMet), eIF-2, and eIF-2B expression shows that GCN4 translation is inversely coupled to the level of eIF-2.GTP.Met-tRNA(iMet) ternary complexes. Mol Cell Biol. 1995;15:6351-63 pubmed
    ..Met-tRNA(iMet) ternary complexes is the cardinal parameter determining the site of reinitiation on GCN4 mRNA and support the idea that reinitiation at GCN4 is inversely related to the concentration of ternary complexes in the cell. ..
  13. Gárriz A, Qiu H, Dey M, Seo E, Dever T, Hinnebusch A. A network of hydrophobic residues impeding helix alphaC rotation maintains latency of kinase Gcn2, which phosphorylates the alpha subunit of translation initiation factor 2. Mol Cell Biol. 2009;29:1592-607 pubmed publisher
    Kinase Gcn2 is activated by amino acid starvation and downregulates translation initiation by phosphorylating the alpha subunit of translation initiation factor 2 (eIF2alpha)...
  14. Zhu S, Sobolev A, Wek R. Histidyl-tRNA synthetase-related sequences in GCN2 protein kinase regulate in vitro phosphorylation of eIF-2. J Biol Chem. 1996;271:24989-94 pubmed
    In yeast, starvation for amino acids stimulates GCN2 phosphorylation of the alpha subunit of eukaryotic initiation factor-2 (eIF-2)...
  15. Harashima S, Hinnebusch A. Multiple GCD genes required for repression of GCN4, a transcriptional activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. Mol Cell Biol. 1986;6:3990-8 pubmed
    ..GCN4 is coupled to amino acid availability by a control mechanism involving GCD1 as a negative effector and GCN1, GCN2, and GCN3 as positive effectors of GCN4 expression...
  16. Wek S, Zhu S, Wek R. The histidyl-tRNA synthetase-related sequence in the eIF-2 alpha protein kinase GCN2 interacts with tRNA and is required for activation in response to starvation for different amino acids. Mol Cell Biol. 1995;15:4497-506 pubmed
    Protein kinase GCN2 is a multidomain protein that contains a region homologous to histidyl-tRNA synthetases juxtaposed to the kinase catalytic moiety...
  17. Zaborske J, Narasimhan J, Jiang L, Wek S, Dittmar K, Freimoser F, et al. Genome-wide analysis of tRNA charging and activation of the eIF2 kinase Gcn2p. J Biol Chem. 2009;284:25254-67 pubmed publisher
    ..These results also depict a complex cellular relationship between tRNA charging, amino acid availability, and non-nutrient stress. These relationships are best revealed by simultaneous monitoring of the charging level of all tRNAs. ..
  18. Visweswaraiah J, Lageix S, Castilho B, Izotova L, Kinzy T, Hinnebusch A, et al. Evidence that eukaryotic translation elongation factor 1A (eEF1A) binds the Gcn2 protein C terminus and inhibits Gcn2 activity. J Biol Chem. 2011;286:36568-79 pubmed publisher
    ..To ensure a continuous supply of amino acids, cells harbor the kinase Gcn2 and its effector protein Gcn1. The ultimate signal for amino acid shortage is uncharged tRNAs...
  19. Daugeron M, Lenstra T, Frizzarin M, El Yacoubi B, Liu X, Baudin Baillieu A, et al. Gcn4 misregulation reveals a direct role for the evolutionary conserved EKC/KEOPS in the t6A modification of tRNAs. Nucleic Acids Res. 2011;39:6148-60 pubmed publisher
    ..Overall, our data provide a novel twist to understanding the primary function of the EKC/KEOPS and its impact on several essential cellular functions like transcription and telomere homeostasis. ..
  20. Cherkasova V, Qiu H, Hinnebusch A. Snf1 promotes phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 by activating Gcn2 and inhibiting phosphatases Glc7 and Sit4. Mol Cell Biol. 2010;30:2862-73 pubmed publisher
    ..a regulator of general and gene-specific translation, by stimulating the function of eIF2alpha kinase Gcn2 during histidine starvation of glucose-grown cells...
  21. Lee S, Swanson M, Sattlegger E. Gcn1 contacts the small ribosomal protein Rps10, which is required for full activation of the protein kinase Gcn2. Biochem J. 2015;466:547-59 pubmed publisher
    In eukaryotes, amino acid deprivation leads to the accumulation of uncharged tRNAs that are detected by Gcn2 (general control non-derepressible 2), which in turn phosphorylates eIF2α (α-subunit of eukaryotic translation initiation ..
  22. Paddon C, Hannig E, Hinnebusch A. Amino acid sequence similarity between GCN3 and GCD2, positive and negative translational regulators of GCN4: evidence for antagonism by competition. Genetics. 1989;122:551-9 pubmed
    ..A gcd2 deletion and gcd2-1 are each expected to inactivate a second domain for which GCN3 cannot substitute, accounting for the inability of GCN3 to mask the phenotypes associated with these mutations. ..
  23. Richardson J, Mohammad S, Pavitt G. Mutations causing childhood ataxia with central nervous system hypomyelination reduce eukaryotic initiation factor 2B complex formation and activity. Mol Cell Biol. 2004;24:2352-63 pubmed
    ..Altered protein folding is characteristic of other diseases, including cystic fibrosis and neurodegenerative disorders such as Huntington, Alzheimer's, and prion diseases. ..
  24. Wu Z, Song L, Liu S, Huang D. Independent and additive effects of glutamic acid and methionine on yeast longevity. PLoS ONE. 2013;8:e79319 pubmed publisher
    ..This study may help to fill a gap in yeast model for the fast developing view that nutrient balance is a critical factor to extend lifespan. ..
  25. Vazquez de Aldana C, Dever T, Hinnebusch A. Mutations in the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2 alpha) that overcome the inhibitory effect of eIF-2 alpha phosphorylation on translation initiation. Proc Natl Acad Sci U S A. 1993;90:7215-9 pubmed
    Phosphorylation of eIF-2 alpha in Saccharomyces cerevisiae by the protein kinase GCN2 leads to inhibition of general translation initiation and a specific increase in translation of GCN4 mRNA...
  26. Vazquez de Aldana C, Hinnebusch A. Mutations in the GCD7 subunit of yeast guanine nucleotide exchange factor eIF-2B overcome the inhibitory effects of phosphorylated eIF-2 on translation initiation. Mol Cell Biol. 1994;14:3208-22 pubmed
    ..In Saccharomyces cerevisiae, phosphorylation of eIF-2 alpha by the protein kinase GCN2 specifically stimulates translation of GCN4 mRNA in addition to reducing general protein synthesis...
  27. Hoffmann B, Mösch H, Sattlegger E, Barthelmess I, Hinnebusch A, Braus G. The WD protein Cpc2p is required for repression of Gcn4 protein activity in yeast in the absence of amino-acid starvation. Mol Microbiol. 1999;31:807-22 pubmed
    ..Loss of CPC2 gene function suppresses a deletion of the GCN2 gene encoding the general control sensor kinase, but not a deletion in the GCN4 gene...
  28. Greenberg M, Myers P, Skvirsky R, Greer H. New positive and negative regulators for general control of amino acid biosynthesis in Saccharomyces cerevisiae. Mol Cell Biol. 1986;6:1820-9 pubmed
    ..A mutation in the negative regulator GCD5 was isolated on the basis of its suppression of a gcn2 mutation. The effect of gcd5 is a posttranscriptional increase in histidine biosynthetic enzyme activity...
  29. Hinnebusch A. Evidence for translational regulation of the activator of general amino acid control in yeast. Proc Natl Acad Sci U S A. 1984;81:6442-6 pubmed
    ..Starvation for histidine leads to derepression of the fusion enzyme in the wild type but not in a gcn2- strain...
  30. Cuesta R, Hinnebusch A, Tamame M. Identification of GCD14 and GCD15, novel genes required for translational repression of GCN4 mRNA in Saccharomyces cerevisiae. Genetics. 1998;148:1007-20 pubmed
    ..Like other known GCD genes, GCD14 and GCD15 are therefore probably required for general translation initiation in addition to their roles in GCN4-specific translational control. ..
  31. Hueso G, Aparicio Sanchis R, Montesinos C, Lorenz S, Murguía J, Serrano R. A novel role for protein kinase Gcn2 in yeast tolerance to intracellular acid stress. Biochem J. 2012;441:255-64 pubmed publisher
    ..Another acid-tolerance gene is GCN2, encoding a protein kinase activated by uncharged tRNAs during amino acid starvation...
  32. Deplazes A, Möckli N, Luke B, Auerbach D, Peter M. Yeast Uri1p promotes translation initiation and may provide a link to cotranslational quality control. EMBO J. 2009;28:1429-41 pubmed publisher
    ..Together with genetic data, these interactions indicate that Uri1p may coordinate translation initiation and cotranslational quality control. ..
  33. Feng L, Yoon H, Donahue T. Casein kinase II mediates multiple phosphorylation of Saccharomyces cerevisiae eIF-2 alpha (encoded by SUI2), which is required for optimal eIF-2 function in S. cerevisiae. Mol Cell Biol. 1994;14:5139-53 pubmed
    ..2 (eIF-2 alpha), encoded by the SUI2 gene in the yeast Saccharomyces cerevisiae, is phosphorylated at Ser-51 by the GCN2 kinase in response to general amino acid control...
  34. Jennings M, Pavitt G. eIF5 has GDI activity necessary for translational control by eIF2 phosphorylation. Nature. 2010;465:378-81 pubmed publisher
    ..Together our studies define a new step in the translation initiation pathway, one that is critical for normal translational controls. ..
  35. Rivera Ruiz M, Rodríguez Quiñones J, Akamine P, RODRIGUEZ MEDINA J. Post-transcriptional regulation in the myo1? mutant of Saccharomyces cerevisiae. BMC Genomics. 2010;11:690 pubmed publisher
    ..Deletion of GCN2 in myo1? abolished eIF2?p phosphorylation, and showed a severe growth defect...
  36. Shin B, Kim J, Walker S, Dong J, Lorsch J, Dever T. Initiation factor eIF2γ promotes eIF2-GTP-Met-tRNAi(Met) ternary complex binding to the 40S ribosome. Nat Struct Mol Biol. 2011;18:1227-34 pubmed publisher
    ..Thus, despite their structural similarity, eIF2 and EF-Tu bind tRNAs in substantially different manners, and we propose that the tRNA-binding domain III of EF-Tu has acquired a new ribosome-binding function in eIF2γ. ..
  37. Tate J, Buford D, Rai R, Cooper T. General Amino Acid Control and 14-3-3 Proteins Bmh1/2 Are Required for Nitrogen Catabolite Repression-Sensitive Regulation of Gln3 and Gat1 Localization. Genetics. 2017;205:633-655 pubmed publisher
    ..Present experiments demonstrate that the other previously elusive component is uncharged transfer RNA-activated, Gcn2 protein kinase-mediated general amino acid control (GAAC)...
  38. Yuan W, Guo S, Gao J, Zhong M, Yan G, Wu W, et al. General Control Nonderepressible 2 (GCN2) Kinase Inhibits Target of Rapamycin Complex 1 in Response to Amino Acid Starvation in Saccharomyces cerevisiae. J Biol Chem. 2017;292:2660-2669 pubmed publisher
    In eukaryotic cells, two conserved protein kinases, Gcn2 and TOR complex 1 (TORC1), couple amino acid conditions to protein translation...
  39. Zaborske J, Wu X, Wek R, Pan T. Selective control of amino acid metabolism by the GCN2 eIF2 kinase pathway in Saccharomyces cerevisiae. BMC Biochem. 2010;11:29 pubmed publisher
    When eukaryotic cells are deprived of amino acids, uncharged tRNAs accumulate and activate the conserved GCN2 protein kinase...
  40. Kubota H, Sakaki Y, Ito T. GI domain-mediated association of the eukaryotic initiation factor 2alpha kinase GCN2 with its activator GCN1 is required for general amino acid control in budding yeast. J Biol Chem. 2000;275:20243-6 pubmed
    ..is based on de-repressed translation of GCN4 mRNA, which is induced by the activation of the eIF2alpha kinase, GCN2. Although it is known that in vivo activation of GCN2 requires GCN1, the mode of GCN1 action remains to be ..
  41. Wang H, Kakaradov B, Collins S, Karotki L, Fiedler D, Shales M, et al. A complex-based reconstruction of the Saccharomyces cerevisiae interactome. Mol Cell Proteomics. 2009;8:1361-81 pubmed publisher
  42. Kubota H, Ota K, Sakaki Y, Ito T. Budding yeast GCN1 binds the GI domain to activate the eIF2alpha kinase GCN2. J Biol Chem. 2001;276:17591-6 pubmed
    ..the budding yeast Saccharomyces cerevisiae activates the eukaryotic initiation factor 2alpha (eIF2alpha) kinase GCN2 in a GCN1-dependent manner...
  43. Dev K, Qiu H, Dong J, Zhang F, Barthlme D, Hinnebusch A. The beta/Gcd7 subunit of eukaryotic translation initiation factor 2B (eIF2B), a guanine nucleotide exchange factor, is crucial for binding eIF2 in vivo. Mol Cell Biol. 2010;30:5218-33 pubmed publisher
    ..In aggregate, these findings provide compelling evidence that ?/Gcd7 is crucial for binding of substrate by eIF2B in vivo, beyond its dispensable regulatory role in the inhibition of eIF2B by eIF (?P). ..
  44. Ballester Tomás L, Prieto J, Alepuz P, González A, Garre E, Randez Gil F. Inappropriate translation inhibition and P-body formation cause cold-sensitivity in tryptophan-auxotroph yeast mutants. Biochim Biophys Acta Mol Cell Res. 2017;1864:314-323 pubmed publisher
    ..downregulate protein synthesis through the phosphorylation of eIF2? (eukaryotic initiation factor 2?) by Gcn2, a highly conserved protein kinase...
  45. Perez W, Kinzy T. Translation elongation factor 1A mutants with altered actin bundling activity show reduced aminoacyl-tRNA binding and alter initiation via eIF2? phosphorylation. J Biol Chem. 2014;289:20928-38 pubmed
    ..Deletion of GCN2 from the eEF1A actin bundling mutant strains revealed a second defect in translation...
  46. Valerius O, Kleinschmidt M, Rachfall N, Schulze F, López Marín S, Hoppert M, et al. The Saccharomyces homolog of mammalian RACK1, Cpc2/Asc1p, is required for FLO11-dependent adhesive growth and dimorphism. Mol Cell Proteomics. 2007;6:1968-79 pubmed
    ..A crucial role of Cpc2p/Asc1p at the ribosomal interface coordinating signal transduction, translation initiation, and transcription factor formation was corroborated. ..
  47. Kimpe M, Voordeckers K, Thevelein J, Van Zeebroeck G. Pkh1 interacts with and phosphorylates components of the yeast Gcn2/eIF2? system. Biochem Biophys Res Commun. 2012;419:89-94 pubmed publisher
    ..Accumulation of uncharged tRNAs activates the Gcn2 protein kinase, which phosphorylates the alpha subunit of the eukaryotic initiation factor 2 (eIF2?)...
  48. Waller T, Lee S, Sattlegger E. Evidence that Yih1 resides in a complex with ribosomes. FEBS J. 2012;279:1761-76 pubmed publisher
    ..The eIF2? kinase Gcn2 is essential for overcoming amino acid starvation in all eukaryotes...
  49. Patil C, Li H, Walter P. Gcn4p and novel upstream activating sequences regulate targets of the unfolded protein response. PLoS Biol. 2004;2:E246 pubmed
    ..The discovery of a role for Gcn4p in the yeast UPR reveals an additional level of complexity and demonstrates a surprising conservation of the signaling circuit between yeast and metazoan cells. ..
  50. Zinshteyn B, Gilbert W. Loss of a conserved tRNA anticodon modification perturbs cellular signaling. PLoS Genet. 2013;9:e1003675 pubmed publisher
    ..Instead, we observed activation of the GCN4-mediated stress response by a non-canonical pathway. Thus, loss of mcm(5)s(2)U causes global effects on gene expression due to perturbation of cellular signaling. ..
  51. Yang W, Hinnebusch A. Identification of a regulatory subcomplex in the guanine nucleotide exchange factor eIF2B that mediates inhibition by phosphorylated eIF2. Mol Cell Biol. 1996;16:6603-16 pubmed
    ..Together, our results provide strong evidence that GCN3, GCD7, and the C-terminal half of GCD2 comprise the regulatory domain in eIF2B. ..
  52. Wout P, Sattlegger E, Sullivan S, Maddock J. Saccharomyces cerevisiae Rbg1 protein and its binding partner Gir2 interact on Polyribosomes with Gcn1. Eukaryot Cell. 2009;8:1061-71 pubmed publisher
    ..Gir2 contains a GI (Gcn2 and Impact) domain similar to that of Gcn2, an essential factor of the general amino acid control pathway required ..
  53. VALASEK L, Nielsen K, Zhang F, Fekete C, Hinnebusch A. Interactions of eukaryotic translation initiation factor 3 (eIF3) subunit NIP1/c with eIF1 and eIF5 promote preinitiation complex assembly and regulate start codon selection. Mol Cell Biol. 2004;24:9437-55 pubmed
    ..Thus, the NIP1-NTD is required for efficient assembly of preinitiation complexes and also regulates the selection of AUG start codons in vivo. ..
  54. Rodriguez Hernandez C, Guinovart J, Murguia J. Anti-diabetic and anti-obesity agent sodium tungstate enhances GCN pathway activation through Glc7p inhibition. FEBS Lett. 2012;586:270-6 pubmed publisher
    ..Tungstate relieved the sensitivity to starvation of a gcn2-507 yeast hypomorphic mutant, indicating that tungstate modulated the GCN pathway downstream of Gcn2p...
  55. Aparicio F, Aparicio Sanchis R, Gadea J, Sanchez Navarro J, Pallas V, Murguia J. A plant virus movement protein regulates the Gcn2p kinase in budding yeast. PLoS ONE. 2011;6:e27409 pubmed publisher
    ..Overall, these findings uncover a previously uncharacterised function for PNRSV MP viral protein, and point out at Tor1p and Gcn2p kinases as candidate susceptibility factors for plant viral infections. ..
  56. Sattlegger E, Barbosa J, Moraes M, Martins R, Hinnebusch A, Castilho B. Gcn1 and actin binding to Yih1: implications for activation of the eIF2 kinase GCN2. J Biol Chem. 2011;286:10341-55 pubmed publisher
    Yeast Yih1 protein and its mammalian ortholog IMPACT, abundant in neurons, are inhibitors of Gcn2, a kinase involved in amino acid homeostasis, stress response, and memory formation...
  57. Rojas M, Gingras A, Dever T. Protein phosphatase PP1/GLC7 interaction domain in yeast eIF2? bypasses targeting subunit requirement for eIF2? dephosphorylation. Proc Natl Acad Sci U S A. 2014;111:E1344-53 pubmed publisher
    Whereas the protein kinases GCN2, HRI, PKR, and PERK specifically phosphorylate eukaryotic translation initiation factor 2 (eIF2?) on Ser51 to regulate global and gene-specific mRNA translation, eIF2? is dephosphorylated by the broadly ..
  58. Schäfer T, Strauss D, Petfalski E, Tollervey D, Hurt E. The path from nucleolar 90S to cytoplasmic 40S pre-ribosomes. EMBO J. 2003;22:1370-80 pubmed
    ..Our data provide an initial biochemical map of the pre-40S ribosomal subunit on its path from the nucleolus to the cytoplasm. This pathway involves fewer changes in composition than seen during 60S biogenesis. ..
  59. Lageix S, Zhang J, Rothenburg S, Hinnebusch A. Interaction between the tRNA-binding and C-terminal domains of Yeast Gcn2 regulates kinase activity in vivo. PLoS Genet. 2015;11:e1004991 pubmed publisher
    The stress-activated protein kinase Gcn2 regulates protein synthesis by phosphorylation of translation initiation factor eIF2α...
  60. Dey M, Cao C, Sicheri F, Dever T. Conserved intermolecular salt bridge required for activation of protein kinases PKR, GCN2, and PERK. J Biol Chem. 2007;282:6653-60 pubmed
    The protein kinases PKR, GCN2, and PERK phosphorylate translation initiation factor eIF2alpha to regulate general and genespecific protein synthesis under various cellular stress conditions...
  61. Mascarenhas C, Edwards Ingram L, Zeef L, Shenton D, Ashe M, Grant C. Gcn4 is required for the response to peroxide stress in the yeast Saccharomyces cerevisiae. Mol Biol Cell. 2008;19:2995-3007 pubmed publisher
    ..is entirely dependent on phosphorylation of the alpha subunit of eukaryotic initiation factor (eIF)2 by the Gcn2 kinase...