GCN4

Summary

Gene Symbol: GCN4
Description: amino acid starvation-responsive transcription factor GCN4
Alias: AAS101, AAS3, ARG9, amino acid starvation-responsive transcription factor GCN4
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Qiu H, Hu C, Zhang F, Hwang G, Swanson M, Boonchird C, et al. Interdependent recruitment of SAGA and Srb mediator by transcriptional activator Gcn4p. Mol Cell Biol. 2005;25:3461-74 pubmed
    ..Thus, while Tra1p can bind directly to Gcn4p in vitro, it requires other SAGA subunits for efficient recruitment in vivo. ..
  2. Meimoun A, Holtzman T, Weissman Z, McBride H, Stillman D, Fink G, et al. Degradation of the transcription factor Gcn4 requires the kinase Pho85 and the SCF(CDC4) ubiquitin-ligase complex. Mol Biol Cell. 2000;11:915-27 pubmed
    b>Gcn4, a yeast transcriptional activator that promotes the expression of amino acid and purine biosynthesis genes, is rapidly degraded in rich medium...
  3. Govind C, Yoon S, Qiu H, Govind S, Hinnebusch A. Simultaneous recruitment of coactivators by Gcn4p stimulates multiple steps of transcription in vivo. Mol Cell Biol. 2005;25:5626-38 pubmed
    ..Our findings reveal a program of coactivator recruitment and PIC assembly that distinguishes Gcn4p from other yeast activators studied thus far. ..
  4. Steffen K, MacKay V, Kerr E, Tsuchiya M, Hu D, Fox L, et al. Yeast life span extension by depletion of 60s ribosomal subunits is mediated by Gcn4. Cell. 2008;133:292-302 pubmed publisher
    ..One mechanism by which reduced 60S subunit levels leads to life span extension is through induction of Gcn4, a nutrient-responsive transcription factor...
  5. Szamecz B, Rutkai E, Cuchalová L, Munzarová V, Herrmannová A, Nielsen K, et al. eIF3a cooperates with sequences 5' of uORF1 to promote resumption of scanning by post-termination ribosomes for reinitiation on GCN4 mRNA. Genes Dev. 2008;22:2414-25 pubmed publisher
    ..Strikingly, it also severely blocks the induction of GCN4 translation that occurs via reinitiation...
  6. Kornitzer D, Raboy B, Kulka R, Fink G. Regulated degradation of the transcription factor Gcn4. EMBO J. 1994;13:6021-30 pubmed
    We report that Gcn4, a yeast transcriptional activator of the bZIP family involved in the regulation of the biosynthesis of amino acids and purines, is rapidly turned over...
  7. Yoon S, Qiu H, Swanson M, Hinnebusch A. Recruitment of SWI/SNF by Gcn4p does not require Snf2p or Gcn5p but depends strongly on SWI/SNF integrity, SRB mediator, and SAGA. Mol Cell Biol. 2003;23:8829-45 pubmed
    ..We suggest that SWI/SNF recruitment is enhanced by cooperative interactions with subunits of SRB mediator and SAGA recruited by Gcn4p to the same promoter but is insensitive to histone H3 acetylation by Gcn5p. ..
  8. Qiu H, Hu C, Yoon S, Natarajan K, Swanson M, Hinnebusch A. An array of coactivators is required for optimal recruitment of TATA binding protein and RNA polymerase II by promoter-bound Gcn4p. Mol Cell Biol. 2004;24:4104-17 pubmed
    ..Our results reveal an unexpected complexity in the cofactor requirements for the enhancement of PIC assembly by a single activator protein. ..
  9. Pries R, Bömeke K, Irniger S, Grundmann O, Braus G. Amino acid-dependent Gcn4p stability regulation occurs exclusively in the yeast nucleus. Eukaryot Cell. 2002;1:663-72 pubmed
    ..Therefore, there is a strict spatial separation of protein synthesis and degradation of Gcn4p in yeast. Control of protein stabilization which antagonizes Gcn4p function is restricted to the nucleus. ..

More Information

Publications91

  1. Shemer R, Meimoun A, Holtzman T, Kornitzer D. Regulation of the transcription factor Gcn4 by Pho85 cyclin PCL5. Mol Cell Biol. 2002;22:5395-404 pubmed
    The yeast transcription factor Gcn4 is regulated by amino acid starvation at the levels of both protein synthesis and stability...
  2. Chi Y, Huddleston M, Zhang X, Young R, Annan R, Carr S, et al. Negative regulation of Gcn4 and Msn2 transcription factors by Srb10 cyclin-dependent kinase. Genes Dev. 2001;15:1078-92 pubmed
    The budding yeast transcriptional activator Gcn4 is rapidly degraded in an SCF(Cdc4)-dependent manner in vivo...
  3. Kim S, Swanson M, Qiu H, Govind C, Hinnebusch A. Activator Gcn4p and Cyc8p/Tup1p are interdependent for promoter occupancy at ARG1 in vivo. Mol Cell Biol. 2005;25:11171-83 pubmed
    ..Our findings reveal a novel coactivator function for Cyc8p/Tup1p at the level of activator binding and suggest that Gcn4p may enhance its own binding to the UAS by recruiting Cyc8p/Tup1p. ..
  4. Zhang F, Gaur N, Hasek J, Kim S, Qiu H, Swanson M, et al. Disrupting vesicular trafficking at the endosome attenuates transcriptional activation by Gcn4. Mol Cell Biol. 2008;28:6796-818 pubmed publisher
    ..genes involved in vesicle fusion at the MVB (class C/D vps mutations) impairs transcriptional activation by Gcn4, a global regulator of amino acid biosynthetic genes, by decreasing the ability of chromatin-bound Gcn4 to ..
  5. Cuchalová L, Kouba T, Herrmannová A, Dányi I, Chiu W, Valásek L. The RNA recognition motif of eukaryotic translation initiation factor 3g (eIF3g) is required for resumption of scanning of posttermination ribosomes for reinitiation on GCN4 and together with eIF3i stimulates linear scanning. Mol Cell Biol. 2010;30:4671-86 pubmed publisher
    ..Both mutations also diminish induction of GCN4 expression, which occurs upon starvation via reinitiation...
  6. Rosonina E, Duncan S, Manley J. Sumoylation of transcription factor Gcn4 facilitates its Srb10-mediated clearance from promoters in yeast. Genes Dev. 2012;26:350-5 pubmed publisher
    ..Here we show that the transcriptional activator Gcn4 is sumoylated on two specific lysine residues and in a manner that depends on its ability to bind DNA, indicating ..
  7. Aviram S, Simon E, Gildor T, Glaser F, Kornitzer D. Autophosphorylation-induced degradation of the Pho85 cyclin Pcl5 is essential for response to amino acid limitation. Mol Cell Biol. 2008;28:6858-69 pubmed publisher
    ..Different Pcls target Pho85 to distinct substrates. Pcl5 targets Pho85 specifically to Gcn4, a yeast transcription factor involved in the response to amino acid starvation, eventually causing the degradation ..
  8. Todeschini A, Condon C, Benard L. Sodium-induced GCN4 expression controls the accumulation of the 5' to 3' RNA degradation inhibitor, 3'-phosphoadenosine 5'-phosphate. J Biol Chem. 2006;281:3276-82 pubmed
  9. Yoon S, Hinnebusch A. Mcm1p binding sites in ARG1 positively regulate Gcn4p binding and SWI/SNF recruitment. Biochem Biophys Res Commun. 2009;381:123-8 pubmed publisher
    ..We propose that Mcm1p contributes to active transcription at the ARG1 promoter by increasing the binding of the activator Gcn4p and by recruiting the co-activator complex SWI/SNF at ARG1 under Gcn4p-induced conditions. ..
  10. Ciani B, Bjelic S, Honnappa S, Jawhari H, Jaussi R, Payapilly A, et al. Molecular basis of coiled-coil oligomerization-state specificity. Proc Natl Acad Sci U S A. 2010;107:19850-5 pubmed publisher
    ..By using the archetype coiled-coil domain of the yeast transcriptional activator GCN4 as a model system, we show that well-established trimer-specific oligomerization-state determinants switch the ..
  11. Knutson B, Hahn S. Domains of Tra1 important for activator recruitment and transcription coactivator functions of SAGA and NuA4 complexes. Mol Cell Biol. 2011;31:818-31 pubmed publisher
    ..Our results show that Tra1 recruitment at Gcn4-dependent and Rap1-dependent promoters requires the same regions of Tra1 and that separate regions of Tra1 ..
  12. Pries R, Bömeke K, Draht O, Kunzler M, Braus G. Nuclear import of yeast Gcn4p requires karyopherins Srp1p and Kap95p. Mol Genet Genomics. 2004;271:257-66 pubmed
    ..We have thus identified Gcn4p as a substrate for the Srp1p/Kap95p transport complex. Our data suggest that NLS2 is the essential and specific nuclear transport signal; NLS1 may play only an unspecific or accessory role. ..
  13. Kishi T, Ikeda A, Koyama N, Fukada J, Nagao R. A refined two-hybrid system reveals that SCF(Cdc4)-dependent degradation of Swi5 contributes to the regulatory mechanism of S-phase entry. Proc Natl Acad Sci U S A. 2008;105:14497-502 pubmed publisher
    ..These findings indicate that the SCF(Cdc4) complex regulates S phase entry not only through degradation of Sic1, but also through degradation of Swi5. ..
  14. Melcher K, Johnston S. GAL4 interacts with TATA-binding protein and coactivators. Mol Cell Biol. 1995;15:2839-48 pubmed
    ..This suggests that these two prototypic activators make similar contacts with TBP. ..
  15. Moretto F, Sagot I, Daignan Fornier B, Pinson B. A pharmaco-epistasis strategy reveals a new cell size controlling pathway in yeast. Mol Syst Biol. 2013;9:707 pubmed publisher
    ..This study sheds light on a pathway of >50 genes and illustrates how pharmaco-epistasis applied to yeast offers a potent experimental framework to explore complex genotype/phenotype relationships...
  16. Khakhina S, Johnson S, Manoharlal R, Russo S, Blugeon C, Lemoine S, et al. Control of Plasma Membrane Permeability by ABC Transporters. Eukaryot Cell. 2015;14:442-53 pubmed publisher
  17. Joo Y, Kim J, Kang U, Yu M, Kim J. Gcn4p-mediated transcriptional repression of ribosomal protein genes under amino-acid starvation. EMBO J. 2011;30:859-72 pubmed publisher
    ..Moreover, our results showed evidence of a novel link between general control of amino-acid biosynthesis and ribosome biogenesis mediated by Gcn4p at an early stage of adaptation to amino-acid starvation. ..
  18. Tang X, Orlicky S, Liu Q, Willems A, Sicheri F, Tyers M. Genome-wide surveys for phosphorylation-dependent substrates of SCF ubiquitin ligases. Methods Enzymol. 2005;399:433-58 pubmed
    ..Both methods have identified novel substrates of Cdc4 and may, in principle, be used to identify numerous new substrates of other SCF and SCF-like complexes from yeast to humans. ..
  19. Brandl C, Struhl K. Yeast GCN4 transcriptional activator protein interacts with RNA polymerase II in vitro. Proc Natl Acad Sci U S A. 1989;86:2652-6 pubmed
    ..One such factor, the yeast GCN4 activator protein, binds to the upstream promoter elements of many amino acid biosynthetic genes and induces their ..
  20. Nielsen K, Szamecz B, VALASEK L, Jivotovskaya A, Shin B, Hinnebusch A. Functions of eIF3 downstream of 48S assembly impact AUG recognition and GCN4 translational control. EMBO J. 2004;23:1166-77 pubmed
    ..was rate-limiting in prt1-1 cells, overexpressing TC should suppress the temperature-sensitive phenotype and GCN4 translation should be strongly derepressed in this mutant, but neither was observed...
  21. Yadav K, Rajasekharan R. The transcription factor GCN4 regulates PHM8 and alters triacylglycerol metabolism in Saccharomyces cerevisiae. Curr Genet. 2016;62:841-851 pubmed
    ..General control nonderepressible (GCN4), a basic leucine-zipper transcription factor activates the transcription of amino acids, purine biosynthesis genes ..
  22. Herbig E, Warfield L, Fish L, Fishburn J, Knutson B, Moorefield B, et al. Mechanism of Mediator recruitment by tandem Gcn4 activation domains and three Gal11 activator-binding domains. Mol Cell Biol. 2010;30:2376-90 pubmed publisher
    Targets of the tandem Gcn4 acidic activation domains in transcription preinitiation complexes were identified by site-specific cross-linking...
  23. Gunisova S, Valášek L. Fail-safe mechanism of GCN4 translational control--uORF2 promotes reinitiation by analogous mechanism to uORF1 and thus secures its key role in GCN4 expression. Nucleic Acids Res. 2014;42:5880-93 pubmed publisher
    ..Here, we took advantage of the exemplary model system of reinitiation, the mRNA of yeast transcriptional activator GCN4 containing four short uORFs, and show that contrary to previous reports, not only the first but the first two of ..
  24. Rawal Y, Qiu H, Hinnebusch A. Accumulation of a threonine biosynthetic intermediate attenuates general amino acid control by accelerating degradation of Gcn4 via Pho85 and Cdk8. PLoS Genet. 2014;10:e1004534 pubmed publisher
    b>Gcn4 is a master transcriptional regulator of amino acid and vitamin biosynthetic enzymes subject to the general amino acid control (GAAC), whose expression is upregulated in response to amino acid starvation in Saccharomyces cerevisiae...
  25. Hernández H, Aranda C, Riego L, Gonzalez A. Gln3-Gcn4 hybrid transcriptional activator determines catabolic and biosynthetic gene expression in the yeast Saccharomyces cerevisiae. Biochem Biophys Res Commun. 2011;404:859-64 pubmed publisher
    ..of genes encoding enzymes involved in the amino acid biosynthetic pathways is achieved through the action of the GCN4-encoded transcriptional modulator whose transcriptional activation is induced at the translational level by ..
  26. Bömeke K, Pries R, Korte V, Scholz E, Herzog B, Schulze F, et al. Yeast Gcn4p stabilization is initiated by the dissociation of the nuclear Pho85p/Pcl5p complex. Mol Biol Cell. 2006;17:2952-62 pubmed
  27. Natarajan K, Jackson B, Rhee E, Hinnebusch A. yTAFII61 has a general role in RNA polymerase II transcription and is required by Gcn4p to recruit the SAGA coactivator complex. Mol Cell. 1998;2:683-92 pubmed
    ..Our results provide strong evidence that recruitment of SAGA, in addition to holoenzyme, is crucial for activation by Gcn4p in vivo and that yTAFII61 plays a key role in this process. ..
  28. Neely K, Hassan A, Wallberg A, Steger D, Cairns B, Wright A, et al. Activation domain-mediated targeting of the SWI/SNF complex to promoters stimulates transcription from nucleosome arrays. Mol Cell. 1999;4:649-55 pubmed
    ..The acidic activation domains of VP16, Gcn4, Swi5, and Hap4 interacted directly with the purified SWI/SNF complex and with the SWI/SNF complex in whole-cell ..
  29. McCormick M, Delaney J, Tsuchiya M, Tsuchiyama S, Shemorry A, Sim S, et al. A Comprehensive Analysis of Replicative Lifespan in 4,698 Single-Gene Deletion Strains Uncovers Conserved Mechanisms of Aging. Cell Metab. 2015;22:895-906 pubmed publisher
    ..Moreover, lifespan extension from deletion of LOS1 is nonadditive with DR or mTOR inhibition, and results in Gcn4 transcription factor activation...
  30. 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. ..
  31. Gunišová S, Beznosková P, Mohammad M, Vlčková V, Valášek L. In-depth analysis of cis-determinants that either promote or inhibit reinitiation on GCN4 mRNA after translation of its four short uORFs. RNA. 2016;22:542-58 pubmed publisher
    ..The mRNA of yeast transcriptional activator GCN4 contains four uORFs of both types that together compose an intriguing regulatory mechanism of its expression ..
  32. Kanazawa S, Driscoll M, Struhl K. ATR1, a Saccharomyces cerevisiae gene encoding a transmembrane protein required for aminotriazole resistance. Mol Cell Biol. 1988;8:664-73 pubmed
    ..However, strains containing gcn4 mutations are unable to grow in medium containing aminotriazole because they lack the GCN4 transcriptional ..
  33. Wands A, Wang N, Lum J, Hsieh J, Fierke C, Mapp A. Transient-state kinetic analysis of transcriptional activator·DNA complexes interacting with a key coactivator. J Biol Chem. 2011;286:16238-45 pubmed publisher
    Several lines of evidence suggest that the prototypical amphipathic transcriptional activators Gal4, Gcn4, and VP16 interact with the key coactivator Med15 (Gal11) during transcription initiation despite little sequence homology...
  34. Takemaru K, Harashima S, Ueda H, Hirose S. Yeast coactivator MBF1 mediates GCN4-dependent transcriptional activation. Mol Cell Biol. 1998;18:4971-6 pubmed
    ..Here we provide evidence acquired in vitro and in vivo that yeast MBF1 mediates GCN4-dependent transcriptional activation by bridging the DNA-binding region of GCN4 and TBP...
  35. Hope I, Struhl K. GCN4, a eukaryotic transcriptional activator protein, binds as a dimer to target DNA. EMBO J. 1987;6:2781-4 pubmed
    The eukaryotic transcriptional activator protein, GCN4, synthesized in vitro from the cloned gene, binds specifically to the promoters of yeast amino acid biosynthetic genes...
  36. Peiró Chova L, Estruch F. The yeast RNA polymerase II-associated factor Iwr1p is involved in the basal and regulated transcription of specific genes. J Biol Chem. 2009;284:28958-67 pubmed publisher
  37. Fishburn J, Mohibullah N, Hahn S. Function of a eukaryotic transcription activator during the transcription cycle. Mol Cell. 2005;18:369-78 pubmed
    Site-specific photocrosslinkers positioned within the central transcription-activating region of yeast Gcn4 were used to identify, in an unbiased way, three polypeptides in direct physical proximity to the activator during the process of ..
  38. Valenzuela L, Aranda C, Gonzalez A. TOR modulates GCN4-dependent expression of genes turned on by nitrogen limitation. J Bacteriol. 2001;183:2331-4 pubmed
    ..The results presented in this paper indicate that GCN4 plays a role in the rapamycin-sensitive signaling pathway, regulating the expression of genes involved in the ..
  39. Roussou I, Thireos G, Hauge B. Transcriptional-translational regulatory circuit in Saccharomyces cerevisiae which involves the GCN4 transcriptional activator and the GCN2 protein kinase. Mol Cell Biol. 1988;8:2132-9 pubmed
    b>GCN4 protein mediates the transcriptional activation of amino acid biosynthetic genes in Saccharomyces cerevisiae by specifically binding to DNA sequences in their 5'-regulatory regions...
  40. Torbensen R, Møller H, Gresham D, Alizadeh S, Ochmann D, Boles E, et al. Amino acid transporter genes are essential for FLO11-dependent and FLO11-independent biofilm formation and invasive growth in Saccharomyces cerevisiae. PLoS ONE. 2012;7:e41272 pubmed publisher
    ..Increased intracellular amino acid pools in the PTR3(647::CWNKNPLSSIN)-containing strain opens the possibility that Gap1 regulates the FLO genes through alteration of the amino acid pool sizes. ..
  41. Lin L, Chamberlain L, Zhu L, Green M. Analysis of Gal4-directed transcription activation using Tra1 mutants selectively defective for interaction with Gal4. Proc Natl Acad Sci U S A. 2012;109:1997-2002 pubmed publisher
    ..Finally, we show that although Tra1 is targeted by other activators, these interactions are unaffected by GID mutations, revealing an unanticipated specificity of the Gal4-Tra1 interaction. ..
  42. Crisucci E, Arndt K. Paf1 restricts Gcn4 occupancy and antisense transcription at the ARG1 promoter. Mol Cell Biol. 2012;32:1150-63 pubmed publisher
    ..Rather, by promoting histone H2B lysine 123 ubiquitylation, Paf1 represses the ARG1 gene by negatively affecting Gcn4 occupancy at the promoter...
  43. Herzog B, Popova B, Jakobshagen A, Shahpasandzadeh H, Braus G. Mutual cross talk between the regulators Hac1 of the unfolded protein response and Gcn4 of the general amino acid control of Saccharomyces cerevisiae. Eukaryot Cell. 2013;12:1142-54 pubmed publisher
    ..Hac1 function requires the activity of Gcn4, which mainly acts as a regulator of the general amino acid control network providing Saccharomyces cerevisiae ..
  44. Akhter A, Rosonina E. Chromatin Association of Gcn4 Is Limited by Post-translational Modifications Triggered by its DNA-Binding in Saccharomyces cerevisiae. Genetics. 2016;204:1433-1445 pubmed
    The Saccharomyces cerevisiae transcription factor Gcn4 is expressed during amino acid starvation, and its abundance is controlled by ubiquitin-mediated proteolysis...
  45. Lord C, Ospovat O, Wente S. Nup100 regulates Saccharomyces cerevisiae replicative life span by mediating the nuclear export of specific tRNAs. RNA. 2017;23:365-377 pubmed publisher
    ..Protein levels of the transcription factor Gcn4 are increased when NUP100 is deleted, and GCN4 is required for the elevated life spans of nup100
  46. Tobe B, Kitazono A, Garcia J, Gerber R, Bevis B, Choy J, et al. Morphogenesis signaling components influence cell cycle regulation by cyclin dependent kinase. Cell Div. 2009;4:12 pubmed publisher
    ..The dynamic balance between Cks1- and Swe1-dependent regulation of Cdc28 and, thereby, the timing of mitosis during yeast dimorphism is regulated in part by Ras2/cAMP-mediated PKA signaling, a key pathway controlling filamentous growth. ..
  47. Moxley J, Jewett M, Antoniewicz M, Villas Boas S, Alper H, Wheeler R, et al. Linking high-resolution metabolic flux phenotypes and transcriptional regulation in yeast modulated by the global regulator Gcn4p. Proc Natl Acad Sci U S A. 2009;106:6477-82 pubmed publisher
    ..We anticipate that an integrated approach focusing on metabolic measurements will facilitate construction of more realistic models of cellular regulation for understanding diseases and constructing strains for industrial applications. ..
  48. Swanson M, Qiu H, Sumibcay L, Krueger A, Kim S, Natarajan K, et al. A multiplicity of coactivators is required by Gcn4p at individual promoters in vivo. Mol Cell Biol. 2003;23:2800-20 pubmed
    ..We observed considerable differences in coactivator requirements among several Gcn4p-dependent promoters; thus, only a subset of the array of coactivators that can be recruited by Gcn4p is required at a given target gene in vivo. ..
  49. Bunagan M, Cristian L, Degrado W, Gai F. Truncation of a cross-linked GCN4-p1 coiled coil leads to ultrafast folding. Biochemistry. 2006;45:10981-6 pubmed
    ..Here we have used N-terminal truncation on a cross-linked variant of the GCN4-p1 leucine zipper, aiming to develop a better understanding of the folding mechanism of the coiled-coil motif...
  50. Qiu H, Hu C, Wong C, Hinnebusch A. The Spt4p subunit of yeast DSIF stimulates association of the Paf1 complex with elongating RNA polymerase II. Mol Cell Biol. 2006;26:3135-48 pubmed
    ..spt4Delta reduces trimethylation of Lys4 on histone H3, demonstrating a new role for yeast DSIF in promoting a Paf1C-dependent function in elongation. ..
  51. Wang C, Skinner C, Easlon E, Lin S. Deleting the 14-3-3 protein Bmh1 extends life span in Saccharomyces cerevisiae by increasing stress response. Genetics. 2009;183:1373-84 pubmed publisher
    ..Deleting Bmh1 may eliminate the inhibitory effects of Bmh1 on these longevity factors and therefore extends life span. ..
  52. Streckfuss Bömeke K, Schulze F, Herzog B, Scholz E, Braus G. Degradation of Saccharomyces cerevisiae transcription factor Gcn4 requires a C-terminal nuclear localization signal in the cyclin Pcl5. Eukaryot Cell. 2009;8:496-510 pubmed publisher
    ..cerevisiae cyclin that directs the phosphorylation of the general amino acid control transcriptional activator Gcn4 by the cyclin-dependent kinase (CDK) Pho85...
  53. Mitchell A, Magasanik B. Three regulatory systems control production of glutamine synthetase in Saccharomyces cerevisiae. Mol Cell Biol. 1984;4:2767-73 pubmed
    ..This system operates through the positive regulatory element GCN4. Expression of histidinol dehydrogenase, which is under general control, is not stimulated by glutamine limitation...
  54. Utley R, Ikeda K, Grant P, Cote J, Steger D, Eberharter A, et al. Transcriptional activators direct histone acetyltransferase complexes to nucleosomes. Nature. 1998;394:498-502 pubmed
    ..acetyltransferase (HAT) complexes to the herpesvirus VP16 activation domain and the yeast transcriptional activator Gcn4, and show that it is their interaction with the VP16 activation domain that targets Gal4-VP16-bound nucleosomes for ..
  55. Seong K, Baek J, Ahn B, Yu M, Kim J. Rpn10p is a receptor for ubiquitinated Gcn4p in proteasomal proteolysis. Mol Cells. 2007;24:194-9 pubmed
    b>GCN4 is a typical eukaryotic transcriptional activator that is implicated in the expression of many genes involved in amino acids and purine biosyntheses under stress conditions. It is degraded by 26S proteasomes following ubiquitination...
  56. Vitiello S, Wolfe D, Pearce D. Absence of Btn1p in the yeast model for juvenile Batten disease may cause arginine to become toxic to yeast cells. Hum Mol Genet. 2007;16:1007-16 pubmed
    ..Moreover, deletion of GCN4 (gcn4-Delta), in combination with btn1-Delta, results in a very specific growth requirement for arginine...
  57. Kim Y, McLaughlin N, Lindstrom K, Tsukiyama T, Clark D. Activation of Saccharomyces cerevisiae HIS3 results in Gcn4p-dependent, SWI/SNF-dependent mobilization of nucleosomes over the entire gene. Mol Cell Biol. 2006;26:8607-22 pubmed
    ..We propose that Gcn4p stimulates nucleosome mobilization over the entire HIS3 gene by the SWI/SNF complex. We suggest that the net effect of interplay among remodeling machines at HIS3 is to create a highly dynamic chromatin structure. ..
  58. Teixeira M, Cabrito T, Hanif Z, Vargas R, Tenreiro S, Sá Correia I. Yeast response and tolerance to polyamine toxicity involving the drug : H+ antiporter Qdr3 and the transcription factors Yap1 and Gcn4. Microbiology. 2011;157:945-56 pubmed publisher
    ..is upregulated in yeast cells exposed to spermine or spermidine dependent on the transcription factors Gcn4, which controls amino acid homeostasis, and Yap1, the main regulator of oxidative stress response...
  59. Sosa E, Aranda C, Riego L, Valenzuela L, DeLuna A, Cantu J, et al. Gcn4 negatively regulates expression of genes subjected to nitrogen catabolite repression. Biochem Biophys Res Commun. 2003;310:1175-80 pubmed
    ..Our results uncover the fact that NCR is not solely achieved through the action of Gln3, Gat1, and Ure2. Since Gcn4 regulates the expression of a broad spectrum of genes, the lack of this transcriptional activator could prevent the ..
  60. Saint M, Sawhney S, Sinha I, Singh R, Dahiya R, Thakur A, et al. The TAF9 C-terminal conserved region domain is required for SAGA and TFIID promoter occupancy to promote transcriptional activation. Mol Cell Biol. 2014;34:1547-63 pubmed publisher
    ..Transcriptome profiling performed under Gcn4-activating conditions showed that the Taf9 CRD is required for induced expression of ?9% of the yeast genome...
  61. Barlev N, Candau R, Wang L, Darpino P, Silverman N, Berger S. Characterization of physical interactions of the putative transcriptional adaptor, ADA2, with acidic activation domains and TATA-binding protein. J Biol Chem. 1995;270:19337-44 pubmed
    ..ADA2 associated with the herpesvirus VP16 and yeast GCN4 activation domains but not with the activation domain of yeast HAP4, which previously was shown to be independent ..
  62. Sellers J, Vincent A, Struhl K. Mutations that define the optimal half-site for binding yeast GCN4 activator protein and identify an ATF/CREB-like repressor that recognizes similar DNA sites. Mol Cell Biol. 1990;10:5077-86 pubmed
    The yeast GCN4 transcriptional activator protein binds as a dimer to a dyad-symmetric sequence, indicative of a protein-DNA complex in which two protein monomers interact with adjacent half-sites...
  63. Ng C, Akhter A, Yurko N, Burgener J, Rosonina E, Manley J. Sumoylation controls the timing of Tup1-mediated transcriptional deactivation. Nat Commun. 2015;6:6610 pubmed publisher
    ..We previously showed that the yeast activator Gcn4 becomes sumoylated during activation, facilitating its eventual promoter eviction and transcriptional shut off...
  64. Brzovic P, Heikaus C, Kisselev L, Vernon R, Herbig E, Pacheco D, et al. The acidic transcription activator Gcn4 binds the mediator subunit Gal11/Med15 using a simple protein interface forming a fuzzy complex. Mol Cell. 2011;44:942-53 pubmed publisher
    The structural basis for binding of the acidic transcription activator Gcn4 and one activator-binding domain of the Mediator subunit Gal11/Med15 was examined by NMR...
  65. Batenchuk C, Tepliakova L, Kaern M. Identification of response-modulated genetic interactions by sensitivity-based epistatic analysis. BMC Genomics. 2010;11:493 pubmed publisher
    ..While the method was developed for growth phenotype, it should apply equally well for other phenotypes, including the expression of fluorescent reporters. ..
  66. Nikolaev Y, Pervushin K. Structural basis of RNA binding by leucine zipper GCN4. Protein Sci. 2012;21:667-76 pubmed publisher
    Recently, we showed that leucine zipper (LZ) motifs of basic leucine zipper (bZIP) transcription factors GCN4 and c-Jun are capable of catalyzing degradation of RNA (Nikolaev et al., PLoS ONE 2010; 5:e10765)...
  67. Prochasson P, Neely K, Hassan A, Li B, Workman J. Targeting activity is required for SWI/SNF function in vivo and is accomplished through two partially redundant activator-interaction domains. Mol Cell. 2003;12:983-90 pubmed
    ..Thus, two distinct activator-interaction domains play overlapping roles in the targeting activity of SWI/SNF, which is essential for its function in vivo. ..
  68. Drysdale C, Jackson B, McVeigh R, Klebanow E, Bai Y, Kokubo T, et al. The Gcn4p activation domain interacts specifically in vitro with RNA polymerase II holoenzyme, TFIID, and the Adap-Gcn5p coactivator complex. Mol Cell Biol. 1998;18:1711-24 pubmed
  69. Hope I, Struhl K. Functional dissection of a eukaryotic transcriptional activator protein, GCN4 of yeast. Cell. 1986;46:885-94 pubmed
    Yeast GCN4 protein binds specifically to the promoters of amino acid biosynthetic genes and coordinately induces their transcription...
  70. Tian C, Kasuga T, Sachs M, Glass N. Transcriptional profiling of cross pathway control in Neurospora crassa and comparative analysis of the Gcn4 and CPC1 regulons. Eukaryot Cell. 2007;6:1018-29 pubmed
    ..cerevisiae experiences amino acid starvation. In the filamentous ascomycete Neurospora crassa, the ortholog of GCN4 is called the cross pathway control-1 (cpc-1) gene; it is required for the ability of N...
  71. Arndt K, Fink G. GCN4 protein, a positive transcription factor in yeast, binds general control promoters at all 5' TGACTC 3' sequences. Proc Natl Acad Sci U S A. 1986;83:8516-20 pubmed
    The GCN4 gene is required for the general amino acid control derepression response in yeast. GCN4 protein protects a repeated sequence motif in the 5'-untranslated region of HIS4, HIS3, ILV1, and ILV2 genes subject to general control...
  72. Ulmer T, Yaspan B, Ginsberg M, Campbell I. NMR analysis of structure and dynamics of the cytosolic tails of integrin alpha IIb beta 3 in aqueous solution. Biochemistry. 2001;40:7498-508 pubmed
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    ..activates the GAAC through Gcn2p phosphorylation of translation factor eIF2 and preferential translation of GCN4, a transcription activator. TOR senses nitrogen availability and regulates transcription factors such as Gln3p...
  74. 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
    ..Furthermore, Gcn4 is translationally up-regulated in response to H(2)O(2), and it is required for hydroperoxide resistance...
  75. Martinez J, Bordel S, Hong K, Nielsen J. Gcn4p and the Crabtree effect of yeast: drawing the causal model of the Crabtree effect in Saccharomyces cerevisiae and explaining evolutionary trade-offs of adaptation to galactose through systems biology. FEMS Yeast Res. 2014;14:654-62 pubmed publisher
    ..This was done by showing that the point mutation in RAS2 does not result in a lower growth rate on glucose if it is introduced in a GCN4-negative background.
  76. Howard G, Tansey W. Interaction of Gcn4 with target gene chromatin is modulated by proteasome function. Mol Biol Cell. 2016;27:2735-41 pubmed publisher
    ..Activation of transcription by the yeast activator Gcn4, for example, is attenuated by mutations in the ubiquitin ligase that mediates Gcn4 ubiquitylation or by inhibition ..
  77. Matsuo R, Kubota H, Obata T, Kito K, Ota K, Kitazono T, et al. The yeast eIF4E-associated protein Eap1p attenuates GCN4 translation upon TOR-inactivation. FEBS Lett. 2005;579:2433-8 pubmed
    ..the putative TOR-regulated eIF4E-associated protein Eap1p likely functions downstream of Gcn2p to attenuate GCN4 translation via a mechanism independent of eIF4E-binding, thereby constituting another interface between the two ..
  78. Yao Z, Delorme Axford E, Backues S, Klionsky D. Atg41/Icy2 regulates autophagosome formation. Autophagy. 2015;11:2288-99 pubmed publisher
    ..conditions the expression level of Atg41 increases dramatically and is regulated by the transcription factor Gcn4. This work provides further insight into the mechanism of Atg9 function and the dynamics of sequestering membrane ..
  79. Mösch H, Graf R, Braus G. Sequence-specific initiator elements focus initiation of transcription to distinct sites in the yeast TRP4 promoter. EMBO J. 1992;11:4583-90 pubmed
    Transcription from the yeast TRP4 promoter initiates at two basal (i127 and i76) and three GCN4 dependent (i31, i25 and i12) initiator elements...
  80. Setiaputra D, Ross J, Lu S, Cheng D, Dong M, Yip C. Conformational flexibility and subunit arrangement of the modular yeast Spt-Ada-Gcn5 acetyltransferase complex. J Biol Chem. 2015;290:10057-70 pubmed publisher
    ..Our results relate information of overall SAGA structure with detailed subunit level interactions, improving our understanding of its architecture and flexibility. ..
  81. Law M, Ciccaglione K. Fine-tuning of histone H3 Lys4 methylation during pseudohyphal differentiation by the CDK submodule of RNA polymerase II. Genetics. 2015;199:435-53 pubmed publisher
    ..Interestingly, deleting known FLO11 activators including FLO8, MSS11, MFG1, TEC1, SNF1, KSS1, and GCN4 results in a range of phenotypic suppression...
  82. Joo Y, Kim J, Baek J, Seong K, Han K, Song J, et al. Cooperative regulation of ADE3 transcription by Gcn4p and Bas1p in Saccharomyces cerevisiae. Eukaryot Cell. 2009;8:1268-77 pubmed publisher
    ..Taking these results together, we concluded that Gcn4p is responsible for the basal and inducible expression of the ADE3 gene, while Bas1p is required for its basal expression. ..