Home LiteratureArticle Details
PMID: 1652057 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Physiological and genetic analysis of the carbon regulation of the NAD-dependent glutamate dehydrogenase of Saccharomyces cerevisiae.

Molecular and cellular biology ·Vol. 11 ·No. 9 ·1991-09-00 ·Pages 4455-65

Coschigano PW, Miller SM, Magasanik B

Abstract

We found that cells of Saccharomyces cerevisiae have an elevated level of the NAD-dependent glutamate dehydrogenase (NAD-GDH; encoded by the GDH2 gene) when grown with a nonfermentable carbon source or with limiting amounts of glucose, even in the presence of the repressing nitrogen source glutamine. This regulation was found to be transcriptional, and an upstream activation site (GDH2 UASc) sufficient for activation of transcription during respiratory growth conditions was identified. This UAS was found to be separable from a neighboring element which is necessary for the nitrogen source regulation of the gene, and strains deficient for the GLN3 gene product, required for expression of NAD-GDH during growth with the activating nitrogen source glutamate, were unaffected for the expression of NAD-GDH during growth with activating carbon sources. Two classes of mutations which prevented the normal activation of NAD-GDH in response to growth with nonfermentable carbon sources, but which did not affect the nitrogen-regulated expression of NAD-GDH, were found and characterized. Carbon regulation of GDH2 was found to be normal in hxk2, hap3, and hap4 strains and to be only slightly altered in a ssn6 strain; thus, in comparison with the regulation of previously identified glucose-repressed genes, a new pathway appears to be involved in the regulation of GDH2.

Related Genes
MeSH Terms
Blotting, Northern Carbon/metabolism Cloning, Molecular Cytochrome c Group/genetics Cytochromes c DNA-Binding Proteins Fungal Proteins/metabolism Gene Expression Regulation, Enzymologic Gene Expression Regulation, Fungal Genes, Fungal Glucose/metabolism Glutamate Dehydrogenase/genetics,metabolism Glycoside Hydrolases/genetics Mutation NAD/metabolism Nuclear Proteins Plasmids Repressor Proteins Saccharomyces cerevisiae/enzymology,genetics Saccharomyces cerevisiae Proteins beta-Fructofuranosidase
Chemicals
CYC1 protein, S cerevisiae CYC8 protein, S cerevisiae Cytochrome c Group DNA-Binding Proteins Fungal Proteins Nuclear Proteins Repressor Proteins Saccharomyces cerevisiae Proteins NAD Carbon Cytochromes c Glutamate Dehydrogenase Glycoside Hydrolases beta-Fructofuranosidase Glucose
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Coschigano P W
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
Miller S M
Magasanik B
References (56)
56 references, click to expand
  1. Ammonia assimilation in Saccharomyces cerevisiae as mediated by the two glutamate dehydrogenases. Evidence for the gdhA locus being a structural gene for the NADP-dependent glutamate dehydrogenase.
    Mol Gen Genet. 1974;128(1):73-85 PMID: 4150855
  2. NAD and NADP l-glutamate dehydrogenase activity and ammonium regulation in Aspergillus nidulans.
    J Gen Microbiol. 1973 Sep;78(1):39-46 PMID: 4148302
  3. The structural gene for yeast cytochrome C.
    Proc Natl Acad Sci U S A. 1966 Jun;55(6):1498-504 PMID: 5227668
  4. Isolation of the nuclear yeast genes for citrate synthase and fifteen other mitochondrial proteins by a new screening method.
    EMBO J. 1984 Aug;3(8):1773-81 PMID: 6090126
  5. Upstream activation sites of the CYC1 gene of Saccharomyces cerevisiae are active when inverted but not when placed downstream of the "TATA box".
    Proc Natl Acad Sci U S A. 1984 Dec;81(24):7860-4 PMID: 6096863
  6. Purification and properties of glutamine synthetase from Saccharomyces cerevisiae.
    J Biol Chem. 1983 Jan 10;258(1):119-24 PMID: 6129248
  7. Identification of a glutaminyl-tRNA synthetase mutation Saccharomyces cerevisiae.
    J Bacteriol. 1984 May;158(2):530-4 PMID: 6144664
  8. Biochemical and physiological aspects of glutamine synthetase inactivation in Saccharomyces cerevisiae.
    J Biol Chem. 1984 Oct 10;259(19):12054-62 PMID: 6148344
  9. Regulation of glutamine-repressible gene products by the GLN3 function in Saccharomyces cerevisiae.
    Mol Cell Biol. 1984 Dec;4(12):2758-66 PMID: 6152012
  10. A rapid boiling method for the preparation of bacterial plasmids.
    Anal Biochem. 1981 Jun;114(1):193-7 PMID: 6269464
  11. Heme regulates transcription of the CYC1 gene of S. cerevisiae via an upstream activation site.
    Cell. 1983 Apr;32(4):1279-86 PMID: 6301690
  12. Yeast promoters and lacZ fusions designed to study expression of cloned genes in yeast.
    Methods Enzymol. 1983;101:181-91 PMID: 6310321
  13. One-step gene disruption in yeast.
    Methods Enzymol. 1983;101:202-11 PMID: 6310324
  14. An integrated and simplified approach to cloning into plasmids and single-stranded phages.
    Methods Enzymol. 1983;101:78-89 PMID: 6310343
  15. Distinctly regulated tandem upstream activation sites mediate catabolite repression of the CYC1 gene of S. cerevisiae.
    Cell. 1984 Feb;36(2):503-11 PMID: 6319028
  16. Transformation of intact yeast cells treated with alkali cations.
    J Bacteriol. 1983 Jan;153(1):163-8 PMID: 6336730
  17. A suppressor of SNF1 mutations causes constitutive high-level invertase synthesis in yeast.
    Genetics. 1984 May;107(1):19-32 PMID: 6373495
  18. SUC1 gene of Saccharomyces: a structural gene for the large (glycoprotein) and small (carbohydrate-free) forms of invertase.
    Mol Cell Biol. 1981 May;1(5):469-74 PMID: 6765604
  19. Genetic and biochemical evidence for hexokinase PII as a key enzyme involved in carbon catabolite repression in yeast.
    Mol Gen Genet. 1980;178(3):633-7 PMID: 6993859
  20. Two differentially regulated mRNAs with different 5' ends encode secreted with intracellular forms of yeast invertase.
    Cell. 1982 Jan;28(1):145-54 PMID: 7039847
  21. Mutants of yeast defective in sucrose utilization.
    Genetics. 1981 May;98(1):25-40 PMID: 7040163
  22. Utilization of L-glutamic and 2-oxoglutaric acid as sole sources of carbon by Escherichia coli.
    J Gen Microbiol. 1961 Oct;26:175-83 PMID: 13904003
  23. [REPRESSION OF THE SYNTHESIS OF DPN-DEPENDENT GLUTAMIC ACID DEHYDROGENASE IN SACCHAROMYCES CEREVISIAE BY AMMONIUM IONS].
    Biochem Z. 1963 Dec 3;339:175-85 PMID: 14206226
  24. Genetics of yeast hexokinase.
    Genetics. 1977 Aug;86(4):727-44 PMID: 17248750
  25. Regulation of glutamate dehydrogenases in nit-2 and am mutants of Neurospora crassa.
    J Bacteriol. 1979 Mar;137(3):1333-9 PMID: 35517
  26. Isolation and characterization of yeast mutants defective in intermediary carbon metabolism and in carbon catabolite derepression.
    Mol Gen Genet. 1977 Jul 20;154(2):213-20 PMID: 197391
  27. Beta-D-fructofuranoside fructohydrolase from yeast.
    Methods Enzymol. 1975;42:504-11 PMID: 237205
  28. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  29. Glutamine and ammonia in nitrogen catabolite repression of Saccharomyces cerevisiae.
    Biochem Biophys Res Commun. 1977 Mar 21;75(2):233-9 PMID: 322661
  30. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I.
    J Mol Biol. 1977 Jun 15;113(1):237-51 PMID: 881736
  31. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination.
    Biochemistry. 1977 Oct 18;16(21):4743-51 PMID: 911786
  32. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
    Anal Biochem. 1976 May 7;72:248-54 PMID: 942051
  33. Molecular cloning of the yeast mitochondrial aconitase gene (ACO1) and evidence of a synergistic regulation of expression by glucose plus glutamate.
    Mol Cell Biol. 1990 Jul;10(7):3551-61 PMID: 1972545
  34. Role of NAD-linked glutamate dehydrogenase in nitrogen metabolism in Saccharomyces cerevisiae.
    J Bacteriol. 1990 Sep;172(9):4927-35 PMID: 1975578
  35. The URE2 gene product of Saccharomyces cerevisiae plays an important role in the cellular response to the nitrogen source and has homology to glutathione s-transferases.
    Mol Cell Biol. 1991 Feb;11(2):822-32 PMID: 1990286
  36. Release of two Saccharomyces cerevisiae cytochrome genes, COX6 and CYC1, from glucose repression requires the SNF1 and SSN6 gene products.
    Mol Cell Biol. 1990 Mar;10(3):1297-300 PMID: 2154683
  37. Expression of the gene encoding subunit II of yeast QH2: cytochrome c oxidoreductase is regulated by multiple factors.
    Curr Genet. 1990 Jun;17(6):459-64 PMID: 2167771
  38. Cloning and characterization of the iron-sulfur subunit gene of succinate dehydrogenase from Saccharomyces cerevisiae.
    J Biol Chem. 1990 Jun 25;265(18):10419-23 PMID: 2191948
  39. Structure and regulation of KGD1, the structural gene for yeast alpha-ketoglutarate dehydrogenase.
    Mol Cell Biol. 1989 Jun;9(6):2695-705 PMID: 2503710
  40. Three regulatory systems control expression of glutamine synthetase in Saccharomyces cerevisiae at the level of transcription.
    Mol Gen Genet. 1989 Jun;217(2-3):370-7 PMID: 2570348
  41. Glutamine assimilation pathways in Neurospora crassa growing on glutamine as sole nitrogen and carbon source.
    J Gen Microbiol. 1989 Oct;135(10):2699-707 PMID: 2576659
  42. Identification and characterization of HAP4: a third component of the CCAAT-bound HAP2/HAP3 heteromer.
    Genes Dev. 1989 Aug;3(8):1166-78 PMID: 2676721
  43. Yeast HAP2 and HAP3 activators both bind to the CYC1 upstream activation site, UAS2, in an interdependent manner.
    Cell. 1987 Dec 24;51(6):953-61 PMID: 2826015
  44. Mutational analysis of upstream activation sequence 2 of the CYC1 gene of Saccharomyces cerevisiae: a HAP2-HAP3-responsive site.
    Mol Cell Biol. 1988 Feb;8(2):647-54 PMID: 2832731
  45. The HAP3 regulatory locus of Saccharomyces cerevisiae encodes divergent overlapping transcripts.
    Mol Cell Biol. 1988 Feb;8(2):655-63 PMID: 2832732
  46. Yeast HAP2 and HAP3: transcriptional activators in a heteromeric complex.
    Science. 1988 Apr 15;240(4850):317-21 PMID: 2832951
  47. Regulation of nitrogen assimilation in Saccharomyces cerevisiae: roles of the URE2 and GLN3 genes.
    J Bacteriol. 1988 Feb;170(2):708-13 PMID: 2892826
  48. The SPT6 gene is essential for growth and is required for delta-mediated transcription in Saccharomyces cerevisiae.
    Mol Cell Biol. 1987 Feb;7(2):679-86 PMID: 3029564
  49. The nucleotide sequence of the LPD1 gene encoding lipoamide dehydrogenase in Saccharomyces cerevisiae: comparison between eukaryotic and prokaryotic sequences for related enzymes and identification of potential upstream control sites.
    J Gen Microbiol. 1988 May;134(5):1131-9 PMID: 3058861
  50. Regulation of sugar utilization in Saccharomyces species.
    J Bacteriol. 1987 Nov;169(11):4873-7 PMID: 3312161
  51. Molecular analysis of SSN6, a gene functionally related to the SNF1 protein kinase of Saccharomyces cerevisiae.
    Mol Cell Biol. 1987 Oct;7(10):3637-45 PMID: 3316983
  52. A yeast gene that is essential for release from glucose repression encodes a protein kinase.
    Science. 1986 Sep 12;233(4769):1175-80 PMID: 3526554
  53. Effects of null mutations in the hexokinase genes of Saccharomyces cerevisiae on catabolite repression.
    Mol Cell Biol. 1986 Nov;6(11):4046-52 PMID: 3540605
  54. Cloning and molecular analysis of the HAP2 locus: a global regulator of respiratory genes in Saccharomyces cerevisiae.
    Mol Cell Biol. 1985 Dec;5(12):3410-6 PMID: 3915775
  55. Yeast mutants pleiotropically impaired in the regulation of the two glutamate dehydrogenases.
    Biochem Biophys Res Commun. 1973 Jul 17;53(2):367-72 PMID: 4146147
  56. Absence of involvement of glutamine synthetase and of NAD-linked glutamate dehydrogenase in the nitrogen catabolite repression of arginase and other enzymes in Saccharomyces cerevisiae.
    Biochem Biophys Res Commun. 1974 Sep 9;60(1):150-7 PMID: 4153896
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
1991-09-00
Pages
4455-65
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC361309
Subset
IM
Grants
NIGMS NIH HHS · GM-07446 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]