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Gene Review

GCR1  -  Gcr1p

Saccharomyces cerevisiae S288c

Synonyms: Glycolytic genes transcriptional activator GCR1, LPF10, LPF10W, SIT3, YPL075W
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Disease relevance of GCR1

  • In vivo analysis, using isogenic strains of yeast and Escherichia coli transformed with plasmid DNAs, confirmed the binding of both the trans-acting factor RAP1 and the transcriptional activator GCR1 to cis-acting recognition sites located within the PYK UAS element [1].

High impact information on GCR1

  • In Saccharomyces cerevisiae, efficient expression of glycolytic and translational component genes requires two DNA binding proteins, RAP1 (which binds to UASRPG) and GCR1 (which binds to the CT box) [2].
  • Full-length Rap1p and the amino- and carboxyl-truncated versions of Rap1p were each able to facilitate binding of Gcr1p at an appropriately spaced binding site [3].
  • GCR1 gene function is required for high-level glycolytic gene expression [4].
  • In this report, I demonstrate that GCR1 encodes a DNA binding protein whose ability to bind DNA is dependent on the CTTCC sequence motif [4].
  • Synthetic oligonucleotides, modeled on the UAS element of PYK1, in which the relative positions of the Rap1p- and Gcr1p-binding sites were varied prepared and tested for their ability to function as UAS elements [5].

Biological context of GCR1

  • Binding sites for the global regulatory protein known as repressor activator protein 1 (RAP1)/general regulatory factor 1 (GRF1)/translation upstream factor (TUF) are found in close proximity to one or more CTTCC sequence motifs in the controlling region of GCR1-dependent genes [4].
  • A complex regulatory element from the yeast gene ENO2 modulates GCR1-dependent transcriptional activation [6].
  • We show that, in addition to these factors, expression of SUC2 is affected by mutations in the gene GCR1 that encodes the glycolysis regulatory protein Gcr1p [7].
  • A series of in vivo G methylation protection experiments of the native TPI promoter were carried out with wild-type and gcr1 deletion mutant strains [8].
  • However, mutating both GCR1-binding sites resulted in a 68-fold reduction in the level of expression of the reporter gene [9].

Anatomical context of GCR1


Associations of GCR1 with chemical compounds

  • The GCR1 gene product is required for maximal transcription of yeast glycolytic genes and for growth of yeast strains in media containing glucose as a carbon source [11].
  • Ethanol, sucrose, and maltose continue to repress peroxisomes and peroxisomal enzymes normally and therefore, appear to have GCR1-independent repression mechanisms in H. polymorpha [10].
  • A mutant deleted for the GCR1 gene was additionally deficient in fructose repression [10].
  • The results obtained describe how the cells respond to different irradiation conditions by modulating important gene classes, including those associated with stress defense, ribosomal proteins, histones, ergosterol and GCR1-controlled sugar metabolism [12].
  • Screening of a mutagenized strain carrying a multicopy ENO1-'lacZ fusion plasmid revealed a new mutation affecting most glycolytic enzyme activities in a pattern resembling that caused by gcr1: levels in the range of 10% of wild-type levels on glycerol plus lactate but somewhat higher on glucose [13].

Physical interactions of GCR1

  • In this report we show by in vivo footprinting that the regulatory factor encoded by GCR1 binds to two elements in the 3' half of the PGK UAS [14].
  • Gcr1p is a DNA binding transcription factor that requires Gcr2p for its functions [15].

Regulatory relationships of GCR1

  • Together with use of the two-hybrid system of Fields and Song, they show that Gcr1p in its N-terminal half has a potential transcriptional activating function as well as elements for interaction with Gcr2p, which perhaps acts normally to expose an otherwise cryptic activation domain on Gcr1p [16].
  • DNA gel mobility shift assays and in-vitro DNase I protection experiments mapped a DNA binding site for Gcr1p in the transcriptional control region of the SUC2 gene, next to a previously mapped Mig1p binding site [7].
  • The GCR1 requirement for yeast glycolytic gene expression is suppressed by dominant mutations in the SGC1 gene, which encodes a novel basic-helix-loop-helix protein [11].
  • Transcription of the HXT4 gene is regulated by Gcr1p and Gcr2p in the yeast S. cerevisiae [17].
  • Furthermore, we find that Gcr1p positively influences PGK transcription, although it is not responsible for the carbon source dependent regulation of PGK mRNA synthesis [14].

Other interactions of GCR1


Analytical, diagnostic and therapeutic context of GCR1

  • We carried out a molecular dissection of Rap1p to identify domains contributing to its ability to facilitate binding of Gcr1p [3].
  • Using DNA microarrays, the genomic expression patterns of wild-type and gcr1 mutant yeast growing on various media, with and without glucose, were compared [20].


  1. A simple in vivo footprinting method to examine DNA-protein interactions over the yeast PYK UAS element. Dumitru, I., McNeil, J.B. Nucleic Acids Res. (1994) [Pubmed]
  2. GCR1, a transcriptional activator in Saccharomyces cerevisiae, complexes with RAP1 and can function without its DNA binding domain. Tornow, J., Zeng, X., Gao, W., Santangelo, G.M. EMBO J. (1993) [Pubmed]
  3. Multiple domains of repressor activator protein 1 contribute to facilitated binding of glycolysis regulatory protein 1. López, M.C., Smerage, J.B., Baker, H.V. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  4. GCR1 of Saccharomyces cerevisiae encodes a DNA binding protein whose binding is abolished by mutations in the CTTCC sequence motif. Baker, H.V. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  5. Activation mechanism of the multifunctional transcription factor repressor-activator protein 1 (Rap1p). Drazinic, C.M., Smerage, J.B., López, M.C., Baker, H.V. Mol. Cell. Biol. (1996) [Pubmed]
  6. A complex regulatory element from the yeast gene ENO2 modulates GCR1-dependent transcriptional activation. Willett, C.E., Gelfman, C.M., Holland, M.J. Mol. Cell. Biol. (1993) [Pubmed]
  7. Mutations in GCR1 affect SUC2 gene expression in Saccharomyces cerevisiae. Türkel, S., Turgut, T., López, M.C., Uemura, H., Baker, H.V. Mol. Genet. Genomics (2003) [Pubmed]
  8. Characterization of the DNA-binding activity of GCR1: in vivo evidence for two GCR1-binding sites in the upstream activating sequence of TPI of Saccharomyces cerevisiae. Huie, M.A., Scott, E.W., Drazinic, C.M., Lopez, M.C., Hornstra, I.K., Yang, T.P., Baker, H.V. Mol. Cell. Biol. (1992) [Pubmed]
  9. Concerted action of the transcriptional activators REB1, RAP1, and GCR1 in the high-level expression of the glycolytic gene TPI. Scott, E.W., Baker, H.V. Mol. Cell. Biol. (1993) [Pubmed]
  10. A hexose transporter homologue controls glucose repression in the methylotrophic yeast Hansenula polymorpha. Stasyk, O.V., Stasyk, O.G., Komduur, J., Veenhuis, M., Cregg, J.M., Sibirny, A.A. J. Biol. Chem. (2004) [Pubmed]
  11. The GCR1 requirement for yeast glycolytic gene expression is suppressed by dominant mutations in the SGC1 gene, which encodes a novel basic-helix-loop-helix protein. Nishi, K., Park, C.S., Pepper, A.E., Eichinger, G., Innis, M.A., Holland, M.J. Mol. Cell. Biol. (1995) [Pubmed]
  12. Cell cycle arrest determines the intensity of the global transcriptional response of Saccharomyces cerevisiae to ionizing radiation. De Sanctis, V., Bertozzi, C., Costanzo, G., Di Mauro, E., Negri, R. Radiat. Res. (2001) [Pubmed]
  13. gcr2, a new mutation affecting glycolytic gene expression in Saccharomyces cerevisiae. Uemura, H., Fraenkel, D.G. Mol. Cell. Biol. (1990) [Pubmed]
  14. The yeast protein Gcr1p binds to the PGK UAS and contributes to the activation of transcription of the PGK gene. Henry, Y.A., López, M.C., Gibbs, J.M., Chambers, A., Kingsman, S.M., Baker, H.V., Stanway, C.A. Mol. Gen. Genet. (1994) [Pubmed]
  15. The GCR2 gene is required for the transcriptional activation of retrotransposon Ty2-917 in Saccharomyces cerevisiae. Türkel, S. Biol. Pharm. Bull. (2002) [Pubmed]
  16. Mutations in GCR1, a transcriptional activator of Saccharomyces cerevisiae glycolytic genes, function as suppressors of gcr2 mutations. Uemura, H., Jigami, Y. Genetics (1995) [Pubmed]
  17. Transcription of the HXT4 gene is regulated by Gcr1p and Gcr2p in the yeast S. cerevisiae. Türkel, S., Bisson, L.F. Yeast (1999) [Pubmed]
  18. Role of GCR2 in transcriptional activation of yeast glycolytic genes. Uemura, H., Jigami, Y. Mol. Cell. Biol. (1992) [Pubmed]
  19. The GCR1 gene encodes a positive transcriptional regulator of the enolase and glyceraldehyde-3-phosphate dehydrogenase gene families in Saccharomyces cerevisiae. Holland, M.J., Yokoi, T., Holland, J.P., Myambo, K., Innis, M.A. Mol. Cell. Biol. (1987) [Pubmed]
  20. Understanding the growth phenotype of the yeast gcr1 mutant in terms of global genomic expression patterns. López, M.C., Baker, H.V. J. Bacteriol. (2000) [Pubmed]
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