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

• Strains with deletions in both the CYC8 and TUP1 genes are viable, with phenotypes similar to those of strains with a single deletion [1].
• Mutations of yeast CYC8 or TUP1 genes greatly reduce the degree of glucose repression of many genes and affect other regulatory pathways, including mating type [2].
• The gene was further localized to 3.5 kb by mapping of the CYC8 mRNA and insertional mutagenesis [7].
• The CYC8 gene product lacks consensus sequences for DNA-binding domains, suggesting that its function may be different from classical repressor proteins [7].
• The nucleotide sequence of a 4866-bp fragment, including CYC8, was determined [7].

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

• The CYC8 and TUP1 proteins from yeast cells were detected as closely spaced doublets on Western immunoblots of sodium dodecyl sulfate-polyacrylamide gels [2].
• Functional dissection of the yeast Cyc8-Tup1 transcriptional co-repressor complex [3].
• In a similar vein, we find that TUP1, but not SSN6, is required for proper donor selection [17].
• Both SSN6 and a bifunctional SSN6-beta-galactosidase fusion protein were localized in the nucleus by immunofluorescence staining [13].
• Immunoprecipitation of epitope-tagged complex and reconstitution of the complex from in vitro-translated proteins demonstrated that only the Cyc8 and Tup1 proteins were present in the complex [18].

References