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PMID: 16397762 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S.

Coordinate regulation of multiple and distinct biosynthetic pathways by TOR and PKA kinases in S. cerevisiae.

Current genetics ·Vol. 49 ·No. 5 ·2006-05-00 ·Pages 281-93

Chen JC, Powers T

Abstract

The target of rapamycin (TOR) signaling pathway is an essential regulator of cell growth in eukaryotic cells. In Saccharomyces cerevisiae, TOR controls the expression of many genes involved in a wide array of distinct nutrient-responsive metabolic pathways. By exploring the TOR pathway under different growth conditions, we have identified novel TOR-regulated genes, including genes required for branched-chain amino acid biosynthesis as well as lysine biosynthesis (LYS genes). We show that TOR-dependent control of LYS gene expression occurs independently from previously identified LYS gene regulators and is instead coupled to cAMP-regulated protein kinase A (PKA). Additional genome-wide expression analyses reveal that TOR and PKA coregulate LYS gene expression in a pattern that is remarkably similar to genes within the ribosomal protein and "Ribi" regulon genes required for ribosome biogenesis. Moreover, this pattern of coregulation is distinct from other clusters of TOR/PKA coregulated genes, which includes genes involved in fermentation as well as aerobic respiration, suggesting that control of gene expression by TOR and PKA involves multiple modes of crosstalk. Our results underscore how multiple signaling pathways, general growth conditions, as well as the availability of specific nutrients contribute to the maintenance of appropriate patterns of gene activity in yeast.

MeSH Terms
Cyclic AMP-Dependent Protein Kinases Gene Expression Regulation, Fungal Lysine/biosynthesis,genetics Oligonucleotide Array Sequence Analysis Protein Serine-Threonine Kinases/genetics,physiology Saccharomyces cerevisiae/enzymology,genetics Saccharomyces cerevisiae Proteins/genetics,physiology Signal Transduction
Chemicals
Saccharomyces cerevisiae Proteins Protein Serine-Threonine Kinases target of rapamycin protein, S cerevisiae Cyclic AMP-Dependent Protein Kinases Lysine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Chen Jenny C-Y
Section of Molecular and Cellular Biology, College of Biological Sciences, University of California, Davis, CA 95616, USA.
Powers Ted
References (70)
70 references, click to expand
  1. Rap1p requires Gcr1p and Gcr2p homodimers to activate ribosomal protein and glycolytic genes, respectively.
    Genetics. 2001 May;158(1):133-43 PMID: 11333224
  2. The identification of a second cell cycle control on the HO promoter in yeast: cell cycle regulation of SW15 nuclear entry.
    Cell. 1990 Aug 24;62(4):631-47 PMID: 2167175
  3. Mechanism of metabolic control. Target of rapamycin signaling links nitrogen quality to the activity of the Rtg1 and Rtg3 transcription factors.
    J Cell Biol. 2000 Nov 13;151(4):863-78 PMID: 11076970
  4. Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast.
    Science. 1991 Aug 23;253(5022):905-9 PMID: 1715094
  5. Rpd3p relocation mediates a transcriptional response to rapamycin in yeast.
    Chem Biol. 2004 Mar;11(3):295-9 PMID: 15123258
  6. Tor proteins and protein phosphatase 2A reciprocally regulate Tap42 in controlling cell growth in yeast.
    EMBO J. 1999 May 17;18(10 ):2782-92 PMID: 10329624
  7. Getting started with yeast.
    Methods Enzymol. 1991;194:3-21 PMID: 2005794
  8. Yeast PKA represses Msn2p/Msn4p-dependent gene expression to regulate growth, stress response and glycogen accumulation.
    EMBO J. 1998 Jul 1;17(13):3556-64 PMID: 9649426
  9. Novel sensing mechanisms and targets for the cAMP-protein kinase A pathway in the yeast Saccharomyces cerevisiae.
    Mol Microbiol. 1999 Sep;33(5):904-18 PMID: 10476026
  10. TOR regulates ribosomal protein gene expression via PKA and the Forkhead transcription factor FHL1.
    Cell. 2004 Dec 29;119(7):969-79 PMID: 15620355
  11. Protein kinase A mediates growth-regulated expression of yeast ribosomal protein genes by modulating RAP1 transcriptional activity.
    Mol Cell Biol. 1994 Mar;14(3):1920-8 PMID: 8114723
  12. Partitioning the transcriptional program induced by rapamycin among the effectors of the Tor proteins.
    Curr Biol. 2000 Dec 14-28;10(24):1574-81 PMID: 11137008
  13. Global phenotypic analysis and transcriptional profiling defines the weak acid stress response regulon in Saccharomyces cerevisiae.
    Mol Biol Cell. 2004 Feb;15(2):706-20 PMID: 14617816
  14. Tor signaling and nutrient-based signals converge on Mks1p phosphorylation to regulate expression of Rtg1.Rtg3p-dependent target genes.
    J Biol Chem. 2004 Nov 5;279(45):46527-35 PMID: 15326168
  15. Nutrient availability and the RAS/cyclic AMP pathway both induce expression of ribosomal protein genes in Saccharomyces cerevisiae but by different mechanisms.
    Mol Cell Biol. 1995 Jun;15(6):3187-96 PMID: 7760815
  16. A dynamic transcriptional network communicates growth potential to ribosome synthesis and critical cell size.
    Genes Dev. 2004 Oct 15;18(20):2491-505 PMID: 15466158
  17. Acute glucose starvation activates the nuclear localization signal of a stress-specific yeast transcription factor.
    EMBO J. 2002 Jan 15;21(1-2):135-44 PMID: 11782433
  18. Computational identification of cis-regulatory elements associated with groups of functionally related genes in Saccharomyces cerevisiae.
    J Mol Biol. 2000 Mar 10;296(5):1205-14 PMID: 10698627
  19. Sfp1 is a stress- and nutrient-sensitive regulator of ribosomal protein gene expression.
    Proc Natl Acad Sci U S A. 2004 Oct 5;101(40):14315-22 PMID: 15353587
  20. Transcriptome profiling of a Saccharomyces cerevisiae mutant with a constitutively activated Ras/cAMP pathway.
    Physiol Genomics. 2003 Dec 16;16(1):107-18 PMID: 14570984
  21. GCR1, a transcriptional activator in Saccharomyces cerevisiae, complexes with RAP1 and can function without its DNA binding domain.
    EMBO J. 1993 Jun;12(6):2431-7 PMID: 8508768
  22. Transformation of yeast by lithium acetate/single-stranded carrier DNA/polyethylene glycol method.
    Methods Enzymol. 2002;350:87-96 PMID: 12073338
  23. Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration.
    Nature. 2002 Jul 18;418(6895):344-8 PMID: 12124627
  24. Genomic expression programs in the response of yeast cells to environmental changes.
    Mol Biol Cell. 2000 Dec;11(12):4241-57 PMID: 11102521
  25. Lys80p of Saccharomyces cerevisiae, previously proposed as a specific repressor of LYS genes, is a pleiotropic regulatory factor identical to Mks1p.
    Yeast. 1997 Nov;13(14 ):1337-46 PMID: 9392078
  26. Gcn4p, a master regulator of gene expression, is controlled at multiple levels by diverse signals of starvation and stress.
    Eukaryot Cell. 2002 Feb;1(1):22-32 PMID: 12455968
  27. Growth-regulated recruitment of the essential yeast ribosomal protein gene activator Ifh1.
    Nature. 2004 Dec 23;432(7020):1058-61 PMID: 15616569
  28. The expanding TOR signaling network.
    Curr Opin Cell Biol. 2005 Apr;17(2):158-66 PMID: 15780592
  29. Global nucleosome occupancy in yeast.
    Genome Biol. 2004;5(9):R62 PMID: 15345046
  30. Mitochondrial signaling: the retrograde response.
    Mol Cell. 2004 Apr 9;14(1):1-15 PMID: 15068799
  31. In Saccharomyces cerevisae, feedback inhibition of homocitrate synthase isoenzymes by lysine modulates the activation of LYS gene expression by Lys14p.
    Eur J Biochem. 1999 Apr;261(1):163-70 PMID: 10103047
  32. The tor pathway regulates gene expression by linking nutrient sensing to histone acetylation.
    Mol Cell Biol. 2003 Jan;23(2):629-35 PMID: 12509460
  33. PKA and Sch9 control a molecular switch important for the proper adaptation to nutrient availability.
    Mol Microbiol. 2005 Feb;55(3):862-80 PMID: 15661010
  34. Rapamycin-modulated transcription defines the subset of nutrient-sensitive signaling pathways directly controlled by the Tor proteins.
    Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14866-70 PMID: 10611304
  35. ParaMEME: a parallel implementation and a web interface for a DNA and protein motif discovery tool.
    Comput Appl Biosci. 1996 Aug;12(4):303-10 PMID: 8902357
  36. The Sch9 protein kinase in the yeast Saccharomyces cerevisiae controls cAPK activity and is required for nitrogen activation of the fermentable-growth-medium-induced (FGM) pathway.
    Microbiology. 1997 Aug;143 ( Pt 8):2627-37 PMID: 9274016
  37. The TOR signaling cascade regulates gene expression in response to nutrients.
    Genes Dev. 1999 Dec 15;13(24):3271-9 PMID: 10617575
  38. Functional profiling of the Saccharomyces cerevisiae genome.
    Nature. 2002 Jul 25;418(6896):387-91 PMID: 12140549
  39. The transcription factor Ifh1 is a key regulator of yeast ribosomal protein genes.
    Nature. 2004 Dec 23;432(7020):1054-8 PMID: 15616568
  40. Retrograde signaling is regulated by the dynamic interaction between Rtg2p and Mks1p.
    Mol Cell. 2003 Aug;12(2):401-11 PMID: 14536080
  41. The economics of ribosome biosynthesis in yeast.
    Trends Biochem Sci. 1999 Nov;24(11):437-40 PMID: 10542411
  42. Elucidating TOR signaling and rapamycin action: lessons from Saccharomyces cerevisiae.
    Microbiol Mol Biol Rev. 2002 Dec;66(4):579-91, table of contents PMID: 12456783
  43. Glucose-sensing and -signalling mechanisms in yeast.
    FEMS Yeast Res. 2002 May;2(2):183-201 PMID: 12702307
  44. Central role of Ifh1p-Fhl1p interaction in the synthesis of yeast ribosomal proteins.
    EMBO J. 2005 Feb 9;24(3):533-42 PMID: 15692568
  45. TOR and PKA signaling pathways converge on the protein kinase Rim15 to control entry into G0.
    Mol Cell. 2003 Dec;12 (6):1607-13 PMID: 14690612
  46. The genome-wide localization of Rsc9, a component of the RSC chromatin-remodeling complex, changes in response to stress.
    Mol Cell. 2002 Mar;9(3):563-73 PMID: 11931764
  47. Transcriptional profiling shows that Gcn4p is a master regulator of gene expression during amino acid starvation in yeast.
    Mol Cell Biol. 2001 Jul;21(13):4347-68 PMID: 11390663
  48. Exploring the metabolic and genetic control of gene expression on a genomic scale.
    Science. 1997 Oct 24;278(5338):680-6 PMID: 9381177
  49. EBP2 is a member of the yeast RRB regulon, a transcriptionally coregulated set of genes that are required for ribosome and rRNA biosynthesis.
    Mol Cell Biol. 2001 Dec;21(24):8638-50 PMID: 11713296
  50. Nutrients, via the Tor proteins, stimulate the association of Tap42 with type 2A phosphatases.
    Genes Dev. 1996 Aug 1;10(15):1904-16 PMID: 8756348
  51. Regulation of longevity and stress resistance by Sch9 in yeast.
    Science. 2001 Apr 13;292(5515):288-90 PMID: 11292860
  52. Tor and cyclic AMP-protein kinase A: two parallel pathways regulating expression of genes required for cell growth.
    Eukaryot Cell. 2005 Jan;4(1):63-71 PMID: 15643061
  53. Two yeast homologs of ECA39, a target for c-Myc regulation, code for cytosolic and mitochondrial branched-chain amino acid aminotransferases.
    J Biol Chem. 1996 Aug 23;271(34):20242-5 PMID: 8702755
  54. Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae.
    Yeast. 1998 Jul;14(10):953-61 PMID: 9717241
  55. Regulation of ribosome biogenesis by the rapamycin-sensitive TOR-signaling pathway in Saccharomyces cerevisiae.
    Mol Biol Cell. 1999 Apr;10(4):987-1000 PMID: 10198052
  56. Activation of the RAS/cyclic AMP pathway suppresses a TOR deficiency in yeast.
    Mol Cell Biol. 2004 Jan;24(1):338-51 PMID: 14673167
  57. The GCR1 gene encodes a positive transcriptional regulator of the enolase and glyceraldehyde-3-phosphate dehydrogenase gene families in Saccharomyces cerevisiae.
    Mol Cell Biol. 1987 Feb;7(2):813-20 PMID: 3547083
  58. TIP41 interacts with TAP42 and negatively regulates the TOR signaling pathway.
    Mol Cell. 2001 Nov;8(5):1017-26 PMID: 11741537
  59. Sfp1 plays a key role in yeast ribosome biogenesis.
    Eukaryot Cell. 2003 Oct;2(5):1061-8 PMID: 14555489
  60. Repression of the genes for lysine biosynthesis in Saccharomyces cerevisiae is caused by limitation of Lys14-dependent transcriptional activation.
    Mol Cell Biol. 1994 Oct;14(10):6411-8 PMID: 7935367
  61. Identification of a novel one-carbon metabolism regulon in Saccharomyces cerevisiae.
    J Biol Chem. 2004 Feb 20;279(8):7072-81 PMID: 14645232
  62. Nutrient-regulated protein kinases in budding yeast.
    Cell. 2002 Oct 18;111(2):155-8 PMID: 12408859
  63. Chromatin-mediated regulation of nucleolar structure and RNA Pol I localization by TOR.
    EMBO J. 2003 Nov 17;22(22):6045-56 PMID: 14609951
  64. Nutrient signaling through TOR kinases controls gene expression and cellular differentiation in fungi.
    Curr Top Microbiol Immunol. 2004;279:53-72 PMID: 14560951
  65. Designer deletion strains derived from Saccharomyces cerevisiae S288C: a useful set of strains and plasmids for PCR-mediated gene disruption and other applications.
    Yeast. 1998 Jan 30;14(2):115-32 PMID: 9483801
  66. Multiple roles of Tap42 in mediating rapamycin-induced transcriptional changes in yeast.
    Mol Cell. 2003 Jun;11(6):1467-78 PMID: 12820961
  67. Mks1 in concert with TOR signaling negatively regulates RTG target gene expression in S. cerevisiae.
    Curr Biol. 2002 Mar 5;12(5):389-95 PMID: 11882290
  68. Integration of growth factor and nutrient signaling: implications for cancer biology.
    Mol Cell. 2003 Aug;12(2):271-80 PMID: 14536067
  69. Loss of compartmentalization causes misregulation of lysine biosynthesis in peroxisome-deficient yeast cells.
    Eukaryot Cell. 2002 Dec;1(6):978-86 PMID: 12477798
  70. Ras and Gpa2 mediate one branch of a redundant glucose signaling pathway in yeast.
    PLoS Biol. 2004 May;2(5):E128 PMID: 15138498
Article Info
Journal
Current genetics
Abbr.
Curr Genet
ISSN
0172-8083
Published
2006-05-00
Epub
2006-00-06
Pages
281-93
Language
English
Region
United States
NLM ID
8004904
Subset
IM
Analysis Services
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