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Gene Review

CYC8  -  Cyc8p

Saccharomyces cerevisiae S288c

Synonyms: CRT8, General transcriptional corepressor CYC8, Glucose repression mediator protein CYC8, SSN6, YBR0908, ...
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Disease relevance of CYC8

  • Mutations in either TUP1 or CYC8 eliminate or reduce glucose repression of many repressible genes and induce other phenotypes, including flocculence, failure to sporulate, and sterility of MAT alpha cells [1].
  • We raised polyclonal antibodies against TrpE-CYC8 and TrpE-TUP1 fusion proteins expressed in Escherichia coli [2].

High impact information on CYC8

  • Here we show that when it is bound upstream of a functional promoter through the LexA DNA-binding domain, Tup1 represses transcription in the absence of Cyc8 [3].
  • In addition, we show that the Cyc8-Tup1 complex functions both as a corepressor and an inhibitor of Mig1, a protein that binds to promoters of glucose-repressible genes [4].
  • We found Nhp6a/b yeast HMG-box chromatin-associated architectural factors and Ssn6 (Cyc8) corepressor to be crucial transcriptional coactivators of FRE2 gene [5].
  • DNA-bound LexA-MIG1 represses transcription of a target gene in glucose-grown cells, and repression requires SSN6 and TUP1 [6].
  • Here we present evidence that MIG1, a zinc-finger protein in the EGR1/Zif268 family, recruits SSN6-TUP1 to glucose-repressed promoters [6].

Biological context of CYC8


Associations of CYC8 with chemical compounds

  • The TUP1 and CYC8 (= SSN6) genes of Saccharomyces cerevisiae play a major role in glucose repression [1].
  • Deletion of CYC8 confers sensitivity to an inhibitor of isoleucine/valine biosynthesis and impairs activation of Gcn4p-dependent reporters and authentic amino acid biosynthetic target genes [8].
  • Also, the transcriptional regulator CYC8, which mediates glucose derepression, was required for adaptation to citric acid to allow cells to metabolize excess citrate via the tricarboxylic acid (TCA) cycle [9].
  • These data, together with previous genetic evidence, establish a functional and physical interaction between the Cyc8-Tup1 corepressor and the RNA pol II holoenzyme and support a central role of the Mediator complex in transcriptional repression [10].
  • The SFL2 gene encodes a 669-amino acid protein which has domains rich in glutamine, as does the SSN6 protein [11].

Physical interactions of CYC8

  • The Cyc8p/Tup1p complex mediates repression of diverse genes in Saccharomyces cerevisiae and is recruited by DNA binding proteins specific for the different sets of repressed genes [8].
  • Mig1p inhibits gene expression in glucose by binding the Cyc8p (Ssn6p)-Tup1p repressor to the promoter of glucose-repressible genes [12].

Enzymatic interactions of CYC8

  • Here, we show that the C terminus of SSN6 is phosphorylated in vivo and that the SNF1 kinase is not responsible for most of the phosphorylation [13].

Other interactions of CYC8

  • By screening the yeast deletion library, we identified Cyc8p as a coactivator for Gcn4p, a transcriptional activator of amino acid biosynthetic genes [8].
  • In the yeast Saccharomyces cerevisiae, glucose repression of SUC2 transcription requires the SSN6-TUP1 repressor complex [14].
  • We demonstrate that deletion of SSN6, TUP1 or CRT1 alleviated the TAF(II) dependence of the RNR genes, indicating that TAF(II) dependence requires the co-repressor complex [15].
  • The phosphorylation pattern is affected by mutations in the SNF1-SSN6 pathway, which is involved in glucose repression-depression [16].
  • Whereas a functional SNF1 gene, which encodes a protein kinase, is not required for the phosphorylation of ABF1, a functional SSN6 gene is required for itsd ephosphorylation [16].

Analytical, diagnostic and therapeutic context of CYC8


  1. Characterization of TUP1, a mediator of glucose repression in Saccharomyces cerevisiae. Williams, F.E., Trumbly, R.J. Mol. Cell. Biol. (1990) [Pubmed]
  2. The CYC8 and TUP1 proteins involved in glucose repression in Saccharomyces cerevisiae are associated in a protein complex. Williams, F.E., Varanasi, U., Trumbly, R.J. Mol. Cell. Biol. (1991) [Pubmed]
  3. Functional dissection of the yeast Cyc8-Tup1 transcriptional co-repressor complex. Tzamarias, D., Struhl, K. Nature (1994) [Pubmed]
  4. Distinct TPR motifs of Cyc8 are involved in recruiting the Cyc8-Tup1 corepressor complex to differentially regulated promoters. Tzamarias, D., Struhl, K. Genes Dev. (1995) [Pubmed]
  5. Nhp6 facilitates Aft1 binding and Ssn6 recruitment, both essential for FRE2 transcriptional activation. Fragiadakis, G.S., Tzamarias, D., Alexandraki, D. EMBO J. (2004) [Pubmed]
  6. Repression by SSN6-TUP1 is directed by MIG1, a repressor/activator protein. Treitel, M.A., Carlson, M. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  7. Cloning and characterization of the CYC8 gene mediating glucose repression in yeast. Trumbly, R.J. Gene (1988) [Pubmed]
  8. Activator Gcn4p and Cyc8p/Tup1p are interdependent for promoter occupancy at ARG1 in vivo. Kim, S.J., Swanson, M.J., Qiu, H., Govind, C.K., Hinnebusch, A.G. Mol. Cell. Biol. (2005) [Pubmed]
  9. Evidence of a new role for the high-osmolarity glycerol mitogen-activated protein kinase pathway in yeast: regulating adaptation to citric acid stress. Lawrence, C.L., Botting, C.H., Antrobus, R., Coote, P.J. Mol. Cell. Biol. (2004) [Pubmed]
  10. Hrs1/Med3 is a Cyc8-Tup1 corepressor target in the RNA polymerase II holoenzyme. Papamichos-Chronakis, M., Conlan, R.S., Gounalaki, N., Copf, T., Tzamarias, D. J. Biol. Chem. (2000) [Pubmed]
  11. Cloning of the yeast SFL2 gene: its disruption results in pleiotropic phenotypes characteristic for tup1 mutants. Fujita, A., Matsumoto, S., Kuhara, S., Misumi, Y., Kobayashi, H. Gene (1990) [Pubmed]
  12. Genomic footprinting of Mig1p in the MAL62 promoter. Binding is dependent upon carbon source and competitive with the Mal63p activator. Wang, J., Sirenko, O., Needleman, R. J. Biol. Chem. (1997) [Pubmed]
  13. The N-terminal TPR region is the functional domain of SSN6, a nuclear phosphoprotein of Saccharomyces cerevisiae. Schultz, J., Marshall-Carlson, L., Carlson, M. Mol. Cell. Biol. (1990) [Pubmed]
  14. Synergistic release from glucose repression by mig1 and ssn mutations in Saccharomyces cerevisiae. Vallier, L.G., Carlson, M. Genetics (1994) [Pubmed]
  15. Derepression of DNA damage-regulated genes requires yeast TAF(II)s. Li, B., Reese, J.C. EMBO J. (2000) [Pubmed]
  16. ABF1 is a phosphoprotein and plays a role in carbon source control of COX6 transcription in Saccharomyces cerevisiae. Silve, S., Rhode, P.R., Coll, B., Campbell, J., Poyton, R.O. Mol. Cell. Biol. (1992) [Pubmed]
  17. Role of alpha2 protein in donor locus selection during mating type interconversion. Szeto, L., Broach, J.R. Mol. Cell. Biol. (1997) [Pubmed]
  18. The Cyc8 (Ssn6)-Tup1 corepressor complex is composed of one Cyc8 and four Tup1 subunits. Varanasi, U.S., Klis, M., Mikesell, P.B., Trumbly, R.J. Mol. Cell. Biol. (1996) [Pubmed]
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