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Gene Review

GAL80  -  Gal80p

Saccharomyces cerevisiae S288c

Synonyms: Galactose/lactose metabolism regulatory protein GAL80, YM9827.01, YM9958.12, YML051W
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Disease relevance of GAL80


High impact information on GAL80

  • The yeast genetic network regulating galactose metabolism involves two proteins, Gal3p and Gal80p, that feed back positively and negatively, respectively, on GAL gene expression [3].
  • Direct repeat recombination leading either to plasmid loss or conversion was examined in isogenic strains containing null mutations in the positive activator, GAL4, or the repressor, GAL80 [4].
  • Transcriptional regulation in the galactose regulon of yeast is determined by an interplay between a positive regulatory protein, GAL4, and a negative regulatory protein, GAL80 [5].
  • Moreover, GAL4 fragments bearing these 30 amino acids, when expressed from a strong promoter on multicopy plasmids, free the endogenous GAL4 from inhibition by GAL80 [6].
  • Our studies demonstrate that a given promoter can adapt either binary or graded behavior, and identify the Mig1 and Gal80 genes as necessary for binary versus graded behavior of the Gal1 promoter [7].

Biological context of GAL80

  • The transcriptional activation function of the Saccharomyces cerevisiae GAL4 protein is modulated by the GAL80 and GAL3 proteins [8].
  • The chromosomal and single-copy centromeric plasmid locations of GAL7 were indistinguishable in their response to growth conditions (induction by galactose, repression by glucose) and positive and negative regulatory factors (GAL4 and GAL80) [9].
  • Next we constructed GAL7'-'lacZ fusions, whose upstream activating sequence (UAS) from GAL7 was replaced with a GAL80 fragment containing a UAS-like sequence located in the 5' flanking region of GAL80 [10].
  • To study further the controlled expression of GAL80, we have exploited the gene fusion technique [10].
  • The locations of the various mutations in the modelled Gal1p structure identify domains involved in the interaction with Gal80p and provide a structural explanation for the phenotype of constitutive GAL1 mutations [11].

Anatomical context of GAL80

  • We conclude from our analysis that the ultrasensitivity of the GAL genetic switch is solely because of the shuttling phenomena of the repressor Gal80p across the nuclear membrane [12].

Associations of GAL80 with chemical compounds

  • In the yeast Saccharomyces cerevisiae regulation of the galactose/melibiose regulon rests on a dosage-dependent functional interplay between the positive regulator of transcription, the GAL4 protein, and the negative regulator, GAL80 protein [13].
  • When the chromosomal GAL80 gene in wild-type yeast was replaced with the hybrid gene, the uninduced level, but not the induced level, of the GAL10-encoded enzyme (uridine diphosphoglucose-4-epimerase) was significantly increased [10].
  • By mutating the Lac9 binding sites of the GAL80 promoter, we could show that induction of GAL80 is required to prevent activation of the lactose/galactose regulon in glycerol or glucose plus galactose, whereas the noninduced level of Gal80 is sufficient to completely block Lac9 function in glucose [14].
  • The amino-terminal residue of GAL80 was found to be acetylmethionine [15].
  • Such a gene dosage effect of GAL80 was further pronounced if sucrose, a sugar causing catabolite repression, was added to the growth medium [16].

Physical interactions of GAL80

  • We have found that immunoprecipitation of full-length Gal4p from yeast extracts coprecipitates less Gal80p in the presence than in the absence of Gal3p, galactose, and ATP [17].
  • How GAL3 and galactose activate GAL4 is not understood, but the long-standing notion has been that a galactose derivative formed by catalytic activity of GAL3 is the inducer that interacts with GAL80 or the GAL80-GAL4 complex [8].
  • A disruption of MIG1 interacts synergistically with a disruption of GAL80, a gene involved in galactose induction [18].
  • Gal3p and Gal1p interact with the transcriptional repressor Gal80p to form a complex of 1:1 stoichiometry [19].
  • Crosslinking experiments show that a defined position in the activating peptide is in close proximity to TBP and Gal80 in the two separate reactions and show that binding of the inhibitor blocks binding to TBP [20].

Regulatory relationships of GAL80

  • However, GAL4 strongly activated UAS(G)-SNR6 when GAL80, an interacting protein, was fused to TFIIIC [21].
  • We have reported previously that multiple copies of MRG19 suppress GAL genes in a wild-type but not in a gal80 strain of Saccharomyces cerevisiae [22].

Other interactions of GAL80

  • Experiments employing strains inducible (GAL80) or constitutive (gal80) for GAL10 expression indicate that an additional component of glucose repression is inducer exclusion [23].
  • We have also found that retention of Gal80p by GSTG4AD (amino acids [aa] 768 to 881) is markedly reduced in the presence compared to the absence of Gal3p, galactose, and ATP [17].
  • Here, we describe the isolation and characterization of new interaction mutants of K.lactis GAL1 and GAL80 using a two-hybrid screen [11].
  • The concentration of GAL80 mRNA (determined by a quantitative blot hybridization) was nearly comparable to that of URA3 mRNA, in the wild-type yeast grown in medium with glucose or glycerol [24].
  • In agreement with this idea, multiple copies of MRG19 also suppress beta-galactosidase expression driven by the GAL1 promoter in a GAL80-dependent manner [25].

Analytical, diagnostic and therapeutic context of GAL80


  1. Mutational hypersensitivity of a gene regulatory protein: Saccharomyces cerevisiae Gal80p. Melcher, K. Genetics (2005) [Pubmed]
  2. Peptides selected to bind the Gal80 repressor are potent transcriptional activation domains in yeast. Han, Y., Kodadek, T. J. Biol. Chem. (2000) [Pubmed]
  3. Dual feedback loops in the GAL regulon suppress cellular heterogeneity in yeast. Ramsey, S.A., Smith, J.J., Orrell, D., Marelli, M., Petersen, T.W., de Atauri, P., Bolouri, H., Aitchison, J.D. Nat. Genet. (2006) [Pubmed]
  4. Elevated recombination rates in transcriptionally active DNA. Thomas, B.J., Rothstein, R. Cell (1989) [Pubmed]
  5. Interaction of positive and negative regulatory proteins in the galactose regulon of yeast. Johnston, S.A., Salmeron, J.M., Dincher, S.S. Cell (1987) [Pubmed]
  6. The carboxy-terminal 30 amino acids of GAL4 are recognized by GAL80. Ma, J., Ptashne, M. Cell (1987) [Pubmed]
  7. Cell signaling can direct either binary or graded transcriptional responses. Biggar, S.R., Crabtree, G.R. EMBO J. (2001) [Pubmed]
  8. Overproduction of the GAL1 or GAL3 protein causes galactose-independent activation of the GAL4 protein: evidence for a new model of induction for the yeast GAL/MEL regulon. Bhat, P.J., Hopper, J.E. Mol. Cell. Biol. (1992) [Pubmed]
  9. Expression of the Saccharomyces cerevisiae GAL7 gene on autonomous plasmids. Baker, S.M., Okkema, P.G., Jaehning, J.A. Mol. Cell. Biol. (1984) [Pubmed]
  10. Autogenous regulation of the Saccharomyces cerevisiae regulatory gene GAL80. Igarashi, M., Segawa, T., Nogi, Y., Suzuki, Y., Fukasawa, T. Mol. Gen. Genet. (1987) [Pubmed]
  11. Sites for interaction between Gal80p and Gal1p in Kluyveromyces lactis: structural model of galactokinase based on homology to the GHMP protein family. Menezes, R.A., Amuel, C., Engels, R., Gengenbacher, U., Labahn, J., Hollenberg, C.P. J. Mol. Biol. (2003) [Pubmed]
  12. Quantitative analysis of GAL genetic switch of Saccharomyces cerevisiae reveals that nucleocytoplasmic shuttling of Gal80p results in a highly sensitive response to galactose. Verma, M., Bhat, P.J., Venkatesh, K.V. J. Biol. Chem. (2003) [Pubmed]
  13. Functional domains of the yeast regulatory protein GAL4. Johnston, S.A., Zavortink, M.J., Debouck, C., Hopper, J.E. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  14. Gal80 proteins of Kluyveromyces lactis and Saccharomyces cerevisiae are highly conserved but contribute differently to glucose repression of the galactose regulon. Zenke, F.T., Zachariae, W., Lunkes, A., Breunig, K.D. Mol. Cell. Biol. (1993) [Pubmed]
  15. Purification and characterization of the yeast negative regulatory protein GAL80. Yun, S.J., Hiraoka, Y., Nishizawa, M., Takio, K., Titani, K., Nogi, Y., Fukasawa, T. J. Biol. Chem. (1991) [Pubmed]
  16. Regulation of expression of the galactose gene cluster in Saccharomyces cerevisiae. II. The isolation and dosage effect of the regulatory gene GAL80. Nogi, Y., Shimada, H., Matsuzaki, Y., Hashimoto, H., Fukasawa, T. Mol. Gen. Genet. (1984) [Pubmed]
  17. The Gal3p-Gal80p-Gal4p transcription switch of yeast: Gal3p destabilizes the Gal80p-Gal4p complex in response to galactose and ATP. Sil, A.K., Alam, S., Xin, P., Ma, L., Morgan, M., Lebo, C.M., Woods, M.P., Hopper, J.E. Mol. Cell. Biol. (1999) [Pubmed]
  18. Control of yeast GAL genes by MIG1 repressor: a transcriptional cascade in the glucose response. Nehlin, J.O., Carlberg, M., Ronne, H. EMBO J. (1991) [Pubmed]
  19. Gal3p and Gal1p interact with the transcriptional repressor Gal80p to form a complex of 1:1 stoichiometry. Timson, D.J., Ross, H.C., Reece, R.J. Biochem. J. (2002) [Pubmed]
  20. A transcriptional activating region with two contrasting modes of protein interaction. Ansari, A.Z., Reece, R.J., Ptashne, M. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  21. A RNA polymerase III-based two-hybrid system to study RNA polymerase II transcriptional regulators. Marsolier, M.C., Prioleau, M.N., Sentenac, A. J. Mol. Biol. (1997) [Pubmed]
  22. Molecular characterization of MRG19 of Saccharomyces cerevisiae. Implication in the regulation of galactose and nonfermentable carbon source utilization. Khanday, F.A., Saha, M., Bhat, P.J. Eur. J. Biochem. (2002) [Pubmed]
  23. A GAL10-CYC1 hybrid yeast promoter identifies the GAL4 regulatory region as an upstream site. Guarente, L., Yocum, R.R., Gifford, P. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  24. Controlled transcription of the yeast regulatory gene GAL80. Shimada, H., Fukasawa, T. Gene (1985) [Pubmed]
  25. Multiple copies of MRG19 suppress transcription of the GAL1 promoter in a GAL80-dependent manner in Saccharomyces cerevisiae. Kabir, M.A., Khanday, F.A., Mehta, D.V., Bhat, P.J. Mol. Gen. Genet. (2000) [Pubmed]
  26. Purification and characterization of the yeast transcriptional activator GAL4. Parthun, M.R., Jaehning, J.A. J. Biol. Chem. (1990) [Pubmed]
  27. Replacement of a conserved tyrosine by tryptophan in Gal3p of Saccharomyces cerevisiae reduces constitutive activity: implications for signal transduction in the GAL regulon. Lakshminarasimhan, A., Bhat, P.J. Mol. Genet. Genomics (2005) [Pubmed]
  28. Interaction between transcriptional activator protein LAC9 and negative regulatory protein GAL80. Salmeron, J.M., Langdon, S.D., Johnston, S.A. Mol. Cell. Biol. (1989) [Pubmed]
  29. Reconstitution of mRNA editing in yeast using a Gal4-apoB-Gal80 fusion transcript as the selectable marker. Lellek, H., Welker, S., Diehl, I., Kirsten, R., Greeve, J. J. Biol. Chem. (2002) [Pubmed]
  30. Molecular cloning of the GAL80 gene from Saccharomyces cerevisiae and characterization of a gal80 deletion. Yocum, R.R., Johnston, M. Gene (1984) [Pubmed]
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