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Gene Review

DIG2  -  Dig2p

Saccharomyces cerevisiae S288c

Synonyms: D8035.23, Down-regulator of invasive growth 2, RST2, Regulator of STE12 protein 2, Regulator of sterile twelve 2, ...
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Disease relevance of DIG2


High impact information on DIG2

  • DIG2 is pheromone-inducible, whereas DIG1 is constitutively expressed [2].
  • Collectively, these findings indicate that Dig1, and most likely Dig2, are physiological substrates of Kssl and suggest that they regulate Ste12 function by direct protein-protein interaction [2].
  • Differential regulation of transcription: repression by unactivated mitogen-activated protein kinase Kss1 requires the Dig1 and Dig2 proteins [3].
  • Furthermore, disruption of dig1, but not dig2, causes elevated transcriptional activation by a LexA-Ste12p(216-688) fusion [4].
  • RST2 turned out to be identical to HRR25, a gene encoding a dual-specificity casein kinase I in yeast [5].

Biological context of DIG2

  • In the present study, we cloned the wild-type RST2 gene by complementation of the cold-sensitive phenotype of the rst2-1 mutant [5].
  • Homozygous deletion of both RST1 and RST2 (rst-) causes a/alpha diploid cells constitutively to express a-specific genes and mate preferentially as a-cells [1].
  • The encoded protein has a single DNA binding homeodomain but lacks both a C2H2 zinc finger DNA binding domain and an apparent Dig1/Dig2 regulatory motif [6].
  • The fbp1(+) promoter contains two regulatory elements, UAS1 and UAS2, one of which (UAS2) serves as a binding site for two antagonizing C(2)H(2) Zn finger transcription factors, the Rst2 activator and the Scr1 repressor [7].

Associations of DIG2 with chemical compounds

  • In contrast, recombinant glutathione S-transferase-Dig2p binds to the Ste12p DNA-binding domain (DBD) [4].
  • Consistent with this notion, Scr1 is quickly exported from the nucleus to the cytoplasm at the initial stage of derepression, immediately after glucose starvation, at which time Rst2 is known to be imported into the nucleus [7].

Regulatory relationships of DIG2

  • These results demonstrate that Dig1p and Dig2p do not function by redundant mechanisms but rather inhibit pheromone-responsive transcription through interactions with separate regions of Ste12p [4].

Other interactions of DIG2

  • Rst1 and Rst2 were prominent substrates in kinase reactions of Fus3 immune complexes from pheromone-treated cells [8].
  • RST1DS is a dominant mutation and causes elevated expression of Sec12p. rst2 and rst3 are recessive and give pleiotropic phenotypes including slow growth at low temperatures and heterogeneous modification of Sec12p [9].

Analytical, diagnostic and therapeutic context of DIG2


  1. Rst1 and Rst2 are required for the a/alpha diploid cell type in yeast. Gelli, A. Mol. Microbiol. (2002) [Pubmed]
  2. Two novel targets of the MAP kinase Kss1 are negative regulators of invasive growth in the yeast Saccharomyces cerevisiae. Cook, J.G., Bardwell, L., Kron, S.J., Thorner, J. Genes Dev. (1996) [Pubmed]
  3. Differential regulation of transcription: repression by unactivated mitogen-activated protein kinase Kss1 requires the Dig1 and Dig2 proteins. Bardwell, L., Cook, J.G., Zhu-Shimoni, J.X., Voora, D., Thorner, J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  4. Two regulators of Ste12p inhibit pheromone-responsive transcription by separate mechanisms. Olson, K.A., Nelson, C., Tai, G., Hung, W., Yong, C., Astell, C., Sadowski, I. Mol. Cell. Biol. (2000) [Pubmed]
  5. The inactive form of a yeast casein kinase I suppresses the secretory defect of the sec12 mutant. Implication of negative regulation by the Hrr25 kinase in the vesicle budding from the endoplasmic reticulum. Murakami, A., Kimura, K., Nakano, A. J. Biol. Chem. (1999) [Pubmed]
  6. Candida glabrata STE12 is required for wild-type levels of virulence and nitrogen starvation induced filamentation. Calcagno, A.M., Bignell, E., Warn, P., Jones, M.D., Denning, D.W., Mühlschlegel, F.A., Rogers, T.R., Haynes, K. Mol. Microbiol. (2003) [Pubmed]
  7. Reciprocal nuclear shuttling of two antagonizing zn finger proteins modulates tup family corepressor function to repress chromatin remodeling. Hirota, K., Hoffman, C.S., Ohta, K. Eukaryotic Cell (2006) [Pubmed]
  8. Regulation of the mating pheromone and invasive growth responses in yeast by two MAP kinase substrates. Tedford, K., Kim, S., Sa, D., Stevens, K., Tyers, M. Curr. Biol. (1997) [Pubmed]
  9. Identification and characterization of extragenic suppressors of the yeast sec12 ts mutation. Nakano, A. J. Biochem. (1996) [Pubmed]
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