Gcn4p, a Master Regulator of Gene Expression, Is Controlled at Multiple Levels by Diverse Signals of Starvation and Stress

All cells undergo rapid transcriptional reprogramming in response to environmental changes by mobilizing transcriptional activators and repressors. Transcriptional activator proteins function by binding to specific DNA sequences and recruiting the transcriptional machinery to the promoters of genes

[1]  M. Stitzel,et al.  The proteasome regulates the UV-induced activation of the AP-1-like transcription factor Gcn4. , 2001, Genes & development.

[2]  A. Hinnebusch,et al.  The tRNA‐binding moiety in GCN2 contains a dimerization domain that interacts with the kinase domain and is required for tRNA binding and kinase activation , 2001, The EMBO journal.

[3]  K. Zhou,et al.  Structure of yeast regulatory gene LEU3 and evidence that LEU3 itself is under general amino acid control , 1987, Nucleic Acids Res..

[4]  G. Braus,et al.  Repression of GCN4 mRNA Translation by Nitrogen Starvation in Saccharomyces cerevisiae * , 2001, The Journal of Biological Chemistry.

[5]  D. Botstein,et al.  The transcriptional program of sporulation in budding yeast. , 1998, Science.

[6]  A. Hinnebusch 5 Mechanism and Regulation of Initiator Methionyl-tRNA Binding to Ribosomes , 2000 .

[7]  P. Brown,et al.  Exploring the metabolic and genetic control of gene expression on a genomic scale. , 1997, Science.

[8]  P. Brown,et al.  Identification of the Copper Regulon in Saccharomyces cerevisiae by DNA Microarrays* , 2000, The Journal of Biological Chemistry.

[9]  G. Fink,et al.  Degradation of the transcription factor Gcn4 requires the kinase Pho85 and the SCF(CDC4) ubiquitin-ligase complex. , 2000, Molecular biology of the cell.

[10]  R. Marians,et al.  A complex containing two transcription factors regulates peroxisome proliferation and the coordinate induction of beta-oxidation enzymes in Saccharomyces cerevisiae , 1997, Molecular and cellular biology.

[11]  A. Schmidt,et al.  The TOR nutrient signalling pathway phosphorylates NPR1 and inhibits turnover of the tryptophan permease , 1998, The EMBO journal.

[12]  M. Proft,et al.  The Sko1p Repressor and Gcn4p Activator Antagonistically Modulate Stress-Regulated Transcription inSaccharomyces cerevisiae , 2001, Molecular and Cellular Biology.

[13]  L. Samson,et al.  Global response of Saccharomyces cerevisiae to an alkylating agent. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[14]  G. Fink,et al.  BAS1 has a Myb motif and activates HIS4 transcription only in combination with BAS2. , 1989, Science.

[15]  D. Botstein,et al.  Genomic expression programs in the response of yeast cells to environmental changes. , 2000, Molecular biology of the cell.

[16]  S. Han,et al.  An Activator Binding Module of Yeast RNA Polymerase II Holoenzyme , 1999, Molecular and Cellular Biology.

[17]  A. Hinnebusch,et al.  The WD protein Cpc2p is required for repression of Gcn4 protein activity in yeast in the absence of amino‐acid starvation , 1999, Molecular microbiology.

[18]  R. Sood,et al.  A Mammalian Homologue of GCN 2 Protein Kinase Important for Translational Control by Phosphorylation of Eukaryotic Initiation Factor-2 a , 2000 .

[19]  J. Caldwell,et al.  Cloning of an intracellular receptor for protein kinase C: a homolog of the beta subunit of G proteins. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[20]  M. Künzler,et al.  Amino Acid and Adenine Cross-pathway Regulation Act through the Same 5′-TGACTC-3′ Motif in the Yeast HIS7 Promoter* , 1996, The Journal of Biological Chemistry.

[21]  Three regulatory systems control production of glutamine synthetase in Saccharomyces cerevisiae. , 1984, Molecular and cellular biology.

[22]  G. Church,et al.  Finding DNA regulatory motifs within unaligned noncoding sequences clustered by whole-genome mRNA quantitation , 1998, Nature Biotechnology.

[23]  D. Lockhart,et al.  Expression monitoring by hybridization to high-density oligonucleotide arrays , 1996, Nature Biotechnology.

[24]  R. Young,et al.  RNA Polymerase II Holoenzymes and Subcomplexes* , 1998, The Journal of Biological Chemistry.

[25]  C. de Haro,et al.  Characterization of a mammalian homolog of the GCN2 eukaryotic initiation factor 2alpha kinase. , 1999, European journal of biochemistry.

[26]  E. Dubois,et al.  Control of enzyme synthesis in the lysine biosynthetic pathway of Saccharomyces cerevisiae. Evidence for a regulatory role of gene LYS14. , 1988, European journal of biochemistry.

[27]  A. Hinnebusch,et al.  7 Translational Control of GCN4: Gene-specific Regulation by Phosphorylation of elF2 , 1996 .

[28]  B. Daignan-Fornier,et al.  Coregulation of purine and histidine biosynthesis by the transcriptional activators BAS1 and BAS2. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[29]  A. Hinnebusch,et al.  Translation of the yeast transcriptional activator GCN4 is stimulated by purine limitation: implications for activation of the protein kinase GCN2 , 1993, Molecular and cellular biology.

[30]  J. Yates,et al.  Direct analysis of protein complexes using mass spectrometry , 1999, Nature Biotechnology.

[31]  J. Broach,et al.  The Molecular biology of the yeast Saccharomyces : metabolism and gene expression , 1982 .

[32]  D. Sterner,et al.  Inhibition of TATA-Binding Protein Function by SAGA Subunits Spt3 and Spt8 at Gcn4-Activated Promoters , 2000, Molecular and Cellular Biology.

[33]  E. Lander,et al.  Remodeling of yeast genome expression in response to environmental changes. , 2001, Molecular biology of the cell.

[34]  G. Welsh,et al.  Regulation of eukaryotic initiation factor eIF2B: glycogen synthase kinase‐3 phosphorylates a conserved serine which undergoes dephosphorylation in response to insulin , 1998, FEBS letters.

[35]  Y. Ohsumi Molecular mechanism of autophagy in yeast, Saccharomyces cerevisiae. , 1999, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[36]  B. Daignan-Fornier,et al.  Synthesis of glutamine, glycine and 10-formyl tetrahydrofolate is coregulated with purine biosynthesis in Saccharomyces cerevisiae , 1998, Molecular and General Genetics MGG.

[37]  A. Hinnebusch A hierarchy of trans-acting factors modulates translation of an activator of amino acid biosynthetic genes in Saccharomyces cerevisiae , 1985, Molecular and cellular biology.

[38]  C. R. Vázquez de Aldana,et al.  GCN20, a novel ATP binding cassette protein, and GCN1 reside in a complex that mediates activation of the eIF‐2 alpha kinase GCN2 in amino acid‐starved cells. , 1995, The EMBO journal.

[39]  H. Tabak,et al.  Pip2p: a transcriptional regulator of peroxisome proliferation in the yeast Saccharomyces cerevisiae. , 1996, The EMBO journal.

[40]  Y. Sakaki,et al.  GI Domain-mediated Association of the Eukaryotic Initiation Factor 2α Kinase GCN2 with Its Activator GCN1 Is Required for General Amino Acid Control in Budding Yeast* , 2000, The Journal of Biological Chemistry.

[41]  R. Wek,et al.  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 , 1995, Molecular and cellular biology.

[42]  I. Barthelmess,et al.  cpc-2, a new locus involved in general control of amino acid synthetic enzymes in Neurospora crassa , 1990, Current Genetics.

[43]  D. Botstein,et al.  Genomic binding sites of the yeast cell-cycle transcription factors SBF and MBF , 2001, Nature.

[44]  M. Ptashne,et al.  Activators and targets , 1990, Nature.

[45]  D. Botstein,et al.  Genome-wide characterization of the Zap1p zinc-responsive regulon in yeast. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[46]  M. Marton,et al.  Transcriptional Profiling Shows that Gcn4p Is a Master Regulator of Gene Expression during Amino Acid Starvation in Yeast , 2001, Molecular and Cellular Biology.

[47]  S. Schreiber,et al.  Rapamycin-modulated transcription defines the subset of nutrient-sensitive signaling pathways directly controlled by the Tor proteins. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[48]  A. Hinnebusch,et al.  Defects in tRNA Processing and Nuclear Export InduceGCN4 Translation Independently of Phosphorylation of the α Subunit of Eukaryotic Translation Initiation Factor 2 , 2000, Molecular and Cellular Biology.

[49]  A. Hinnebusch,et al.  Association of GCN1–GCN20 regulatory complex with the N‐terminus of eIF2α kinase GCN2 is required for GCN2 activation , 2000, The EMBO journal.

[50]  K. Natarajan,et al.  Transcriptional activation by Gcn4p involves independent interactions with the SWI/SNF complex and the SRB/mediator. , 1999, Molecular cell.

[51]  G. Braus Aromatic amino acid biosynthesis in the yeast Saccharomyces cerevisiae: a model system for the regulation of a eukaryotic biosynthetic pathway. , 1991, Microbiological reviews.

[52]  M. De Rijcke,et al.  The ARG11 Gene of Saccharomyces cerevisiae Encodes a Mitochondrial Integral Membrane Protein Required for Arginine Biosynthesis* , 1996, The Journal of Biological Chemistry.

[53]  H. Frohnmeyer,et al.  Gcn2 Mediates Gcn4 Activation in Response to Glucose Stimulation or UV Radiation Not via GCN4 Translation* , 2001, The Journal of Biological Chemistry.

[54]  M. Schapira,et al.  Regulated translation initiation controls stress-induced gene expression in mammalian cells. , 2000, Molecular cell.

[55]  A. Hinnebusch,et al.  Separate domains in GCN1 for binding protein kinase GCN2 and ribosomes are required for GCN2 activation in amino acid‐starved cells , 2000, The EMBO journal.

[56]  C. Lions,et al.  The transcriptional regulator Hap1p (Cyp1p) is essential for anaerobic or heme-deficient growth of Saccharomyces cerevisiae: Genetic and molecular characterization of an extragenic suppressor that encodes a WD repeat protein. , 1998, Genetics.

[57]  J. Heitman,et al.  The TOR signaling cascade regulates gene expression in response to nutrients. , 1999, Genes & development.

[58]  John J. Wyrick,et al.  Genome-wide location and function of DNA binding proteins. , 2000, Science.

[59]  A. Hinnebusch,et al.  Association of RAP1 binding sites with stringent control of ribosomal protein gene transcription in Saccharomyces cerevisiae , 1991, Molecular and cellular biology.

[60]  T. Powers,et al.  MOLECULAR BIOLOGY OF THE CELL , 1999 .

[61]  S. Emr,et al.  Autophagy as a regulated pathway of cellular degradation. , 2000, Science.

[62]  G. Fink,et al.  Multiple global regulators control HIS4 transcription in yeast. , 1987, Science.

[63]  Cloning of an intracellular receptor for protein kinase C: A homolog of the β subunit of G proteins , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[64]  G. Fink,et al.  Regulated degradation of the transcription factor Gcn4. , 1994, The EMBO journal.

[65]  M. Marton,et al.  Evidence that GCN1 and GCN20, translational regulators of GCN4, function on elongating ribosomes in activation of eIF2alpha kinase GCN2 , 1997, Molecular and cellular biology.

[66]  D. Ron,et al.  15 PERK and Translational Control by Stress in the Endoplasmic Reticulum , 2000 .

[67]  G. Braus,et al.  Monitoring the Gcn4 Protein-mediated Response in the YeastSaccharomyces cerevisiae * , 1998, The Journal of Biological Chemistry.

[68]  P. Hieter,et al.  Detecting patterns of protein distribution and gene expression in silico. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[69]  A. Hinnebusch,et al.  7 General and Pathway-specific Regulatory Mechanisms Controlling the Synthesis of Amino Acid Biosynthetic Enzymes in Saccharomyces cerevisiae , 1992 .

[70]  Mark Johnston,et al.  5 Regulation of Carbon and Phosphate Utilization , 1992 .

[71]  J. D. de Winde,et al.  Involvement of distinct G‐proteins, Gpa2 and Ras, in glucose‐ and intracellular acidification‐induced cAMP signalling in the yeast Saccharomyces cerevisiae , 1998, The EMBO journal.

[72]  L S Robertson,et al.  The yeast A kinases differentially regulate iron uptake and respiratory function. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[73]  Ronald W. Davis,et al.  Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarray , 1995, Science.

[74]  A. Hinnebusch,et al.  The general control of amino acid biosynthetic genes in the yeast Saccharomyces cerevisiae. , 1986, CRC critical reviews in biochemistry.

[75]  A. Hinnebusch,et al.  Uncharged tRNA activates GCN2 by displacing the protein kinase moiety from a bipartite tRNA-binding domain. , 2000, Molecular cell.

[76]  David Botstein,et al.  Promoter-specific binding of Rap1 revealed by genome-wide maps of protein–DNA association , 2001, Nature Genetics.

[77]  A. Hinnebusch Evidence for translational regulation of the activator of general amino acid control in yeast. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[78]  R. Serrano,et al.  The Protein Kinase Gcn2p Mediates Sodium Toxicity in Yeast* , 2001, The Journal of Biological Chemistry.

[79]  R. Young,et al.  Negative regulation of Gcn4 and Msn2 transcription factors by Srb10 cyclin-dependent kinase. , 2001, Genes & development.

[80]  N. Sonenberg,et al.  Translational control of gene expression , 2000 .

[81]  George M. Church,et al.  Regulatory Networks Revealed by Transcriptional Profiling of Damaged Saccharomyces cerevisiae Cells: Rpn4 Links Base Excision Repair with Proteasomes , 2000, Molecular and Cellular Biology.

[82]  K. Struhl,et al.  The UV response involving the ras signaling pathway and AP-1 transcription factors is conserved between yeast and mammals , 1994, Cell.

[83]  A. T.,et al.  On Stringent Response , 1972, Nature.

[84]  A. Hinnebusch,et al.  Multicopy tRNA genes functionally suppress mutations in yeast eIF-2 alpha kinase GCN2: evidence for separate pathways coupling GCN4 expression to unchanged tRNA , 1994, Molecular and cellular biology.

[85]  Dmitrij Frishman,et al.  MIPS: a database for protein sequences and complete genomes , 1998, Nucleic Acids Res..

[86]  L. Yu,et al.  Molecular cloning and mapping of the brain-abundant B1gamma subunit of protein phosphatase 2A, PPP2R2C, to human chromosome 4p16. , 2000, Genomics.

[87]  William Arbuthnot Sir Lane,et al.  Activator-Specific Requirement of Yeast Mediator Proteins for RNA Polymerase II Transcriptional Activation , 1999, Molecular and Cellular Biology.

[88]  M H Saier,et al.  Unified inventory of established and putative transporters encoded within the complete genome of Saccharomyces cerevisiae , 1998, FEBS letters.

[89]  B. M. Jackson,et al.  The Gcn4p Activation Domain Interacts Specifically In Vitro with RNA Polymerase II Holoenzyme, TFIID, and the Adap-Gcn5p Coactivator Complex , 1998, Molecular and Cellular Biology.

[90]  G. Braus,et al.  Transcriptional activation of yeast nucleotide biosynthetic gene ADE4 by GCN4. , 1991, The Journal of biological chemistry.

[91]  G. Thireos,et al.  Coupling of GCN4 mRNA translational activation with decreased rates of polypeptide chain initiation , 1989, Cell.

[92]  A. Goffeau,et al.  Genome microarray analysis of transcriptional activation in multidrug resistance yeast mutants , 2000, FEBS letters.

[93]  G. Fink,et al.  Regulation of Amino Acid and Nucleotide Biosynthesis in Yeast , 1982 .

[94]  R. Sood,et al.  A mammalian homologue of GCN2 protein kinase important for translational control by phosphorylation of eukaryotic initiation factor-2alpha. , 2000, Genetics.

[95]  F. Neidhardt,et al.  Escherichia Coli and Salmonella: Typhimurium Cellular and Molecular Biology , 1987 .

[96]  Cristina Aranda,et al.  TOR Modulates GCN4-Dependent Expression of Genes Turned on by Nitrogen Limitation , 2001, Journal of bacteriology.

[97]  E. O’Shea,et al.  Regulation of nuclear localization: a key to a door. , 1999, Annual review of cell and developmental biology.

[98]  Y. Sakaki,et al.  Budding Yeast GCN1 Binds the GI Domain to Activate the eIF2α Kinase GCN2* , 2001, The Journal of Biological Chemistry.

[99]  M. Jia,et al.  Global expression profiling of yeast treated with an inhibitor of amino acid biosynthesis, sulfometuron methyl. , 2000, Physiological genomics.

[100]  Ruojing Yang,et al.  Glucose Limitation Induces GCN4Translation by Activation of Gcn2 Protein Kinase , 2000, Molecular and Cellular Biology.

[101]  Michael R. Green,et al.  Dissecting the Regulatory Circuitry of a Eukaryotic Genome , 1998, Cell.

[102]  Michael N. Hall,et al.  The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors , 1999, Nature.