• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
Mol Cell Biol. Sep 1989; 9(9): 4091–4095.
PMCID: PMC362479

The CUP2 gene product, regulator of yeast metallothionein expression, is a copper-activated DNA-binding protein.

Abstract

CUP2 is a regulatory gene controlling expression of CUP1, which encodes the Cu-binding yeast metallothionein. CUP2, which is identical to the ACE1 gene, encodes a Cu-regulated DNA-binding protein. The CUP2 protein contains a cysteine-rich DNA-binding domain dependent on Cu+ and Ag+ ions which bind the cysteine residues and direct the refolding of the metal-free apoprotein. CUP2 mutant alleles from Cu-sensitive yeast strains have point mutations affecting the DNA-binding activity. These results establish CUP2 as the primary sensor of intracellular Cu+ in the yeast Saccharomyces cerevisiae, functioning as a Cu+-regulated transcriptional activator.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.2M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Angel P, Allegretto EA, Okino ST, Hattori K, Boyle WJ, Hunter T, Karin M. Oncogene jun encodes a sequence-specific trans-activator similar to AP-1. Nature. 1988 Mar 10;332(6160):166–171. [PubMed]
  • Byrd J, Berger RM, McMillin DR, Wright CF, Hamer D, Winge DR. Characterization of the copper-thiolate cluster in yeast metallothionein and two truncated mutants. J Biol Chem. 1988 May 15;263(14):6688–6694. [PubMed]
  • Fogel S, Welch JW. Tandem gene amplification mediates copper resistance in yeast. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5342–5346. [PMC free article] [PubMed]
  • Fried M, Crothers DM. Equilibria and kinetics of lac repressor-operator interactions by polyacrylamide gel electrophoresis. Nucleic Acids Res. 1981 Dec 11;9(23):6505–6525. [PMC free article] [PubMed]
  • Fürst P, Hu S, Hackett R, Hamer D. Copper activates metallothionein gene transcription by altering the conformation of a specific DNA binding protein. Cell. 1988 Nov 18;55(4):705–717. [PubMed]
  • Garner MM, Revzin A. A gel electrophoresis method for quantifying the binding of proteins to specific DNA regions: application to components of the Escherichia coli lactose operon regulatory system. Nucleic Acids Res. 1981 Jul 10;9(13):3047–3060. [PMC free article] [PubMed]
  • George GN, Byrd J, Winge DR. X-ray absorption studies of yeast copper metallothionein. J Biol Chem. 1988 Jun 15;263(17):8199–8203. [PubMed]
  • Hamer DH. Metallothionein. Annu Rev Biochem. 1986;55:913–951. [PubMed]
  • Hope IA, Struhl K. Functional dissection of a eukaryotic transcriptional activator protein, GCN4 of yeast. Cell. 1986 Sep 12;46(6):885–894. [PubMed]
  • Huibregtse JM, Engelke DR, Thiele DJ. Copper-induced binding of cellular factors to yeast metallothionein upstream activation sequences. Proc Natl Acad Sci U S A. 1989 Jan;86(1):65–69. [PMC free article] [PubMed]
  • Karin M. Metallothioneins: proteins in search of function. Cell. 1985 May;41(1):9–10. [PubMed]
  • Karin M, Najarian R, Haslinger A, Valenzuela P, Welch J, Fogel S. Primary structure and transcription of an amplified genetic locus: the CUP1 locus of yeast. Proc Natl Acad Sci U S A. 1984 Jan;81(2):337–341. [PMC free article] [PubMed]
  • Ma J, Ptashne M. Deletion analysis of GAL4 defines two transcriptional activating segments. Cell. 1987 Mar 13;48(5):847–853. [PubMed]
  • Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, Arnheim N. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science. 1985 Dec 20;230(4732):1350–1354. [PubMed]
  • Szczypka MS, Thiele DJ. A cysteine-rich nuclear protein activates yeast metallothionein gene transcription. Mol Cell Biol. 1989 Feb;9(2):421–429. [PMC free article] [PubMed]
  • Thiele DJ. ACE1 regulates expression of the Saccharomyces cerevisiae metallothionein gene. Mol Cell Biol. 1988 Jul;8(7):2745–2752. [PMC free article] [PubMed]
  • Thiele DJ, Hamer DH. Tandemly duplicated upstream control sequences mediate copper-induced transcription of the Saccharomyces cerevisiae copper-metallothionein gene. Mol Cell Biol. 1986 Apr;6(4):1158–1163. [PMC free article] [PubMed]
  • Welch J, Fogel S, Buchman C, Karin M. The CUP2 gene product regulates the expression of the CUP1 gene, coding for yeast metallothionein. EMBO J. 1989 Jan;8(1):255–260. [PMC free article] [PubMed]
  • Welch JW, Fogel S, Cathala G, Karin M. Industrial yeasts display tandem gene iteration at the CUP1 region. Mol Cell Biol. 1983 Aug;3(8):1353–1361. [PMC free article] [PubMed]
  • Welch JW, Maloney DH, Fogel S. Synaptic relations in meiotic gene conversion at the iterated CUP1r locus of S. cerevisiae. Experientia Suppl. 1987;52:431–437. [PubMed]
  • Winge DR, Nielson KB, Gray WR, Hamer DH. Yeast metallothionein. Sequence and metal-binding properties. J Biol Chem. 1985 Nov 25;260(27):14464–14470. [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • Gene
    Gene
    Gene links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • MedGen
    MedGen
    Related information in MedGen
  • Nucleotide
    Nucleotide
    Published Nucleotide sequences
  • Pathways + GO
    Pathways + GO
    Pathways, annotations and biological systems (BioSystems) that cite the current article.
  • Protein
    Protein
    Published protein sequences
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links
  • Taxonomy
    Taxonomy
    Related taxonomy entry
  • Taxonomy Tree
    Taxonomy Tree

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...