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PMID: 7523855 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Two FK506 resistance-conferring genes in Saccharomyces cerevisiae, TAT1 and TAT2, encode amino acid permeases mediating tyrosine and tryptophan uptake.

Molecular and cellular biology ·Vol. 14 ·No. 10 ·1994-10-00 ·Pages 6597-606

Schmidt A, Hall MN, Koller A

Abstract

The macrocyclic lactone FK506 exerts immunosuppressive effects on T lymphocytes by interfering with signal transduction leading to T-cell activation and also inhibits the growth of eukaryotic microorganisms, including Saccharomyces cerevisiae. We reported previously that an FK506-sensitive target in S. cerevisiae is required for amino acid import and that overexpression of two new genes, TAT1 and TAT2 (formerly called TAP1 and TAP2), confers resistance to the drug. Here we report that TAT1 and TAT2 encode novel members of the yeast amino acid permease family composed of integral membrane proteins that share 30 to 40% identity. TAT1 is the tyrosine high-affinity transporter, which also mediates low-affinity or low-capacity uptake of tryptophan. TAT2 is the tryptophan high-affinity transporter. FK506 does not reduce the levels of TAT1 and TAT2 transcripts, indicating that the inhibition of amino acid transport by the drug is posttranscriptional.

Related Genes
TAT1 TAT2
MeSH Terms
ATP-Binding Cassette Transporters/genetics Amino Acid Sequence Amino Acid Transport Systems Amino Acids/metabolism Base Sequence Biological Transport/genetics Chromosome Mapping Chromosomes, Fungal Drug Resistance, Microbial/genetics Exoribonucleases Fungal Proteins/genetics Genes, Fungal/genetics Membrane Transport Proteins/genetics,metabolism Molecular Sequence Data Mutagenesis Saccharomyces cerevisiae/genetics Saccharomyces cerevisiae Proteins Sequence Analysis, DNA Sequence Homology, Amino Acid Tacrolimus/pharmacology Trans-Activators/genetics Transcription, Genetic Tryptophan/analogs & derivatives,metabolism,pharmacology Tyrosine/metabolism
Chemicals
ATP-Binding Cassette Transporters Amino Acid Transport Systems Amino Acids Fungal Proteins Membrane Transport Proteins Saccharomyces cerevisiae Proteins TAT2 protein, S cerevisiae Trans-Activators RAT1 protein, S cerevisiae 5-fluorotryptophan Tyrosine Tryptophan Exoribonucleases Tacrolimus
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Schmidt A
Department of Biochemistry, Biozentrum, University of Basel, Switzerland.
Hall M N
Koller A
References (41)
41 references, click to expand
  1. Amino acid transport in eucaryotic microorganisms.
    Biochim Biophys Acta. 1986 Dec 22;864(3-4):223-56 PMID: 2947629
  2. Inactivation-reactivation process and repression of permease formation regulate several ammonia-sensitive permeases in the yeast Saccharomyces cerevisiae.
    Eur J Biochem. 1983 Jun 1;133(1):135-9 PMID: 6343083
  3. Isolation of the NPR1 gene responsible for the reactivation of ammonia-sensitive amino-acid permeases in Saccharomyces cerevisiae. RNA analysis and gene dosage effects.
    Eur J Biochem. 1987 May 4;164(3):607-12 PMID: 3552673
  4. Yeast arginine permease: nucleotide sequence of the CAN1 gene.
    Curr Genet. 1986;10(8):587-92 PMID: 3327612
  5. New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base pair restriction sites.
    Gene. 1988 Dec 30;74(2):527-34 PMID: 3073106
  6. Nucleotide sequence of the Saccharomyces cerevisiae PUT4 proline-permease-encoding gene: similarities between CAN1, HIP1 and PUT4 permeases.
    Gene. 1989 Nov 15;83(1):153-9 PMID: 2687114
  7. Mutations in Saccharomyces cerevisiae which confer resistance to several amino acid analogs.
    Mol Cell Biol. 1990 Jun;10(6):2941-9 PMID: 2188104
  8. GAP1, the general amino acid permease gene of Saccharomyces cerevisiae. Nucleotide sequence, protein similarity with the other bakers yeast amino acid permeases, and nitrogen catabolite repression.
    Eur J Biochem. 1990 May 31;190(1):39-44 PMID: 2194797
  9. Chemistry and biology of the immunophilins and their immunosuppressive ligands.
    Science. 1991 Jan 18;251(4991):283-7 PMID: 1702904
  10. The Saccharomyces cerevisiae NPR1 gene required for the activity of ammonia-sensitive amino acid permeases encodes a protein kinase homologue.
    Mol Gen Genet. 1990 Jul;222(2-3):393-9 PMID: 2125693
  11. FK 506-binding protein proline rotamase is a target for the immunosuppressive agent FK 506 in Saccharomyces cerevisiae.
    Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1948-52 PMID: 1705713
  12. DNA of Saccharomyces cerevisiae.
    Methods Enzymol. 1991;194:169-82 PMID: 2005785
  13. Getting started with yeast.
    Methods Enzymol. 1991;194:3-21 PMID: 2005794
  14. Transcriptional activation of yeast nucleotide biosynthetic gene ADE4 by GCN4.
    J Biol Chem. 1991 Oct 25;266(30):20453-6 PMID: 1939099
  15. Aromatic amino acid biosynthesis in the yeast Saccharomyces cerevisiae: a model system for the regulation of a eukaryotic biosynthetic pathway.
    Microbiol Rev. 1991 Sep;55(3):349-70 PMID: 1943992
  16. The complete DNA sequence of yeast chromosome III.
    Nature. 1992 May 7;357(6373):38-46 PMID: 1574125
  17. Structure of the yeast TAP1 protein: dependence of transcription activation on the DNA context of the target gene.
    Mol Cell Biol. 1993 Jun;13(6):3434-44 PMID: 8497260
  18. The immunosuppressant FK506 inhibits amino acid import in Saccharomyces cerevisiae.
    Mol Cell Biol. 1993 Aug;13(8):5010-9 PMID: 7687745
  19. Cloning and sequencing of the Saccharomyces cerevisiae gene LYP1 coding for a lysine-specific permease.
    Yeast. 1993 Jul;9(7):771-82 PMID: 8368011
  20. Cyclosporin A, FK506 and rapamycin: more than just immunosuppression.
    Trends Biochem Sci. 1993 Sep;18(9):334-8 PMID: 7694398
  21. Regulation of the ADE2 gene from Saccharomyces cerevisiae.
    Curr Genet. 1993 Dec;24(6):472-80 PMID: 8299166
  22. Regulation of histidine uptake by specific feedback inhibition of two histidine permeases in Saccharomyces cerevisiae.
    Eur J Biochem. 1970 May 1;14(1):197-204 PMID: 5447432
  23. Amino acid transport in a polyaromatic amino acid auxotroph of Saccharomyces cerevisiae.
    J Bacteriol. 1973 Sep;115(3):975-81 PMID: 4580574
  24. Study of the positive control of the general amino-acid permease and other ammonia-sensitive uptake systems by the product of the NPR1 gene in the yeast Saccharomyces cerevisiae.
    Eur J Biochem. 1983 Jun 1;133(1):141-4 PMID: 6343084
  25. Ammonia regulation of amino acid permeases in Saccharomyces cerevisiae.
    Mol Cell Biol. 1983 Apr;3(4):672-83 PMID: 6343842
  26. Positive regulation in the general amino acid control of Saccharomyces cerevisiae.
    Proc Natl Acad Sci U S A. 1983 Sep;80(17):5374-8 PMID: 6351059
  27. A comprehensive set of sequence analysis programs for the VAX.
    Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 PMID: 6546423
  28. Lariat structures are in vivo intermediates in yeast pre-mRNA splicing.
    Cell. 1984 Dec;39(3 Pt 2):611-21 PMID: 6096014
  29. Molecular characterization of the CAN1 locus in Saccharomyces cerevisiae. A transmembrane protein without N-terminal hydrophobic signal sequence.
    J Biol Chem. 1985 Sep 25;260(21):11831-7 PMID: 3900064
  30. The histidine permease gene (HIP1) of Saccharomyces cerevisiae.
    Gene. 1985;38(1-3):205-14 PMID: 3905514
  31. GCN4 protein, synthesized in vitro, binds HIS3 regulatory sequences: implications for general control of amino acid biosynthetic genes in yeast.
    Cell. 1985 Nov;43(1):177-88 PMID: 3907851
  32. Nitrogen catabolite repression in yeasts and filamentous fungi.
    Adv Microb Physiol. 1985;26:1-88 PMID: 2869649
  33. Saturation mutagenesis of the yeast his3 regulatory site: requirements for transcriptional induction and for binding by GCN4 activator protein.
    Science. 1986 Oct 24;234(4775):451-7 PMID: 3532321
  34. 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 Nov;83(22):8516-20 PMID: 3464968
  35. Possible site-specific reagent for the general amino acid transport system of Saccharomyces cerevisiae.
    Biochemistry. 1978 Feb 7;17(3):431-6 PMID: 339948
  36. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  37. Action of tryptophan analogues in Saccharomyces cerevisiae.
    Arch Microbiol. 1977 Dec 15;115(3):307-16 PMID: 341826
  38. Membrane proteins associated with amino acid transport by yeast (Saccharomyces cerevisiae).
    Biochem J. 1980 Nov 15;192(2):659-64 PMID: 7016114
  39. Transformation of intact yeast cells treated with alkali cations.
    J Bacteriol. 1983 Jan;153(1):163-8 PMID: 6336730
  40. Repeated DNA sequences upstream from HIS1 also occur at several other co-regulated genes in Saccharomyces cerevisiae.
    J Biol Chem. 1983 Apr 25;258(8):5238-47 PMID: 6300123
  41. Nitrogen catabolite regulation of proline permease in Saccharomyces cerevisiae. Cloning of the PUT4 gene and study of PUT4 RNA levels in wild-type and mutant strains.
    Eur J Biochem. 1987 May 4;164(3):601-6 PMID: 3552672
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.14.10.6597-6606.1994
Published
1994-10-00
Pages
6597-606
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC359189
Subset
IM
Databases
GENBANK
X79150, X79151
External Links
PubMed source DOI: 10.1128/mcb.14.10.6597-6606.1994 PMC Full Text View journal details
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