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Gene Review

STE12  -  Ste12p

Saccharomyces cerevisiae S288c

Synonyms: Protein STE12, YHR084W
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Disease relevance of STE12

  • This sterility can be partially suppressed by high-level production of STE12 but is not suppressible by high levels of STE4 or a dominant STE11 truncation allele [1].

High impact information on STE12

  • This condition-dependent distribution of Ste12 requires concurrent binding of the transcription factor Tec1 during filamentation and is differentially regulated by the MAP kinases Fus3 and Kss1 [2].
  • In Saccharomyces, this switch is controlled by two regulatory proteins, Ste12p and Phd1p [3].
  • This indicates that Srb10 controls Ste12 activity for filamentous growth in response to nitrogen limitation and is consistent with the hypothesis that Srb10 regulates gene-specific activators in response to physiological signals to coordinate gene expression with growth potential [4].
  • The results identify pathways that are coordinately regulated by each of the two activators and reveal previously unknown functions for Gal4 and Ste12 [5].
  • In haploid strains of Saccharomyces cerevisiae, a signal initiated by peptide pheromones is transmitted through this kinase cascade to a transcription factor STE12, which is required for the expression of many mating-specific genes [6].

Biological context of STE12


Anatomical context of STE12


Associations of STE12 with chemical compounds

  • In contrast, recombinant glutathione S-transferase-Dig2p binds to the Ste12p DNA-binding domain (DBD) [14].
  • Here it was shown that in diploids some of the same kinases and STE12 are required for filamentous growth, but the pheromone receptors and guanosine triphosphate-binding protein are not required for filament formation [6].
  • Comparison of the CLS12 DNA and protein sequences to other STE12 homologs and transformation experiments with selectable markers from S. cerevisiae (URA3, KanMX, HphMX) and C. albicans (CaURA3) provide evidence that the CUG codon encodes serine instead of leucine in C. lusitaniae, as is also the case in C. albicans [15].
  • Interestingly, the amino acid sequence of the NH2-terminal 215 residues of Acprp is highly similar to the DNA binding domain of Ste12p of Saccharomyces cerevisiae [16].
  • SteAp and Ste12alphap lack the pheromone induction domain found in budding yeast Ste12p, but have C-terminal C2/H2-Zn+2 finger domains not present in the other Ste12 proteins [17].

Physical interactions of STE12

  • Ste12 also binds specifically to GST-Dig1 in the absence of any other yeast protein [18].
  • ARG80 and Agamous exhibit similar DNA binding specificities but do not interact with either STE12 or p62TCF [19].
  • In addition, we show that, while the carboxy-terminal sequences necessary for STE12 to form a complex with the transcription factor MCM1 are not essential for mating, these sequences are required for optimal transcriptional activity [20].
  • We generated a series of hybrid proteins of Ste12p with the DNA-binding and activation domains of the transcriptional activator Gal4p to define a pheromone induction domain of Ste12p sufficient to mediate pheromone-induced transcription by these hybrid proteins [21].
  • Relative to Kss1, the MAPK Fus3 binds less strongly to Ste12 and is correspondingly a weaker inhibitor of invasive growth [22].

Enzymatic interactions of STE12

  • Srb10 inhibits filamentous growth in cells growing in rich medium by phosphorylating Ste12 and decreasing its stability [4].

Regulatory relationships of STE12

  • Mutations in STE12 known to block STE2 mRNA accumulation also resulted in an absence of receptors [23].
  • CONCLUSIONS: Rst1 and Rst2 repress the mating and filamentous growth responses of S. cerevisiae by directly inhibiting Ste12 [24].
  • The activity of the minimal 26 bp UAS from the alpha-specific STE3 gene was both stimulated by pheromone and reduced in ste12 mutants [11].
  • These results suggest that Caf20 and Dhh1 control yeast filamentation by regulating STE12 translation [12].
  • Both Ras2p-controlled signaling pathways stimulate expression of the filamentation response element-driven reporter gene depending on the transcription factors Ste12p and Tec1p, indicating a crosstalk between the MAPK and the cAMP signaling pathways in haploid cells during invasive growth [25].

Other interactions of STE12

  • 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 [18].
  • First, regulation via the MAPK pathway requires the transcription factors Ste12p/Tec1p, whereas cAMP-mediated activation requires a distinct factor, Flo8p [26].
  • Expression of DIG2, but not DIG1, from a GAL promoter inhibits transcriptional activation by an Ste12p DBD-VP16 fusion [14].
  • The cell cycle transcription pattern for FAR1 was changed in ste12- cells: the gene was still significantly expressed in G2/M, but transcript levels were strongly reduced in G1 phase, resulting in a lack of Far1 protein accumulation [27].
  • A 30-bp region upstream of KAR3 conferred both KAR4- and STE12-dependent induction by mating pheromone [28].

Analytical, diagnostic and therapeutic context of STE12

  • We show here that a hybrid protein containing STE12 fused to the DNA-binding domain of GAL4 can activate transcription of a reporter gene containing GAL4-binding sites but only after treatment of cells with pheromone [29].
  • In contrast, ste12 mutant strains have only modest mating defects and are fully virulent in two animal models compared to the STE12 wild-type strain [30].
  • By degenerate PCR, we identified a C. lusitaniae homolog (Cls12) of the Ste12 transcription factor that regulates mating, filamentation, and virulence in Saccharomyces cerevisiae, C. albicans, and Cryptococcus neoformans [15].


  1. A dominant truncation allele identifies a gene, STE20, that encodes a putative protein kinase necessary for mating in Saccharomyces cerevisiae. Ramer, S.W., Davis, R.W. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  2. Program-specific distribution of a transcription factor dependent on partner transcription factor and MAPK signaling. Zeitlinger, J., Simon, I., Harbison, C.T., Hannett, N.M., Volkert, T.L., Fink, G.R., Young, R.A. Cell (2003) [Pubmed]
  3. Nonfilamentous C. albicans mutants are avirulent. Lo, H.J., Köhler, J.R., DiDomenico, B., Loebenberg, D., Cacciapuoti, A., Fink, G.R. Cell (1997) [Pubmed]
  4. Srb10/Cdk8 regulates yeast filamentous growth by phosphorylating the transcription factor Ste12. Nelson, C., Goto, S., Lund, K., Hung, W., Sadowski, I. Nature (2003) [Pubmed]
  5. Genome-wide location and function of DNA binding proteins. Ren, B., Robert, F., Wyrick, J.J., Aparicio, O., Jennings, E.G., Simon, I., Zeitlinger, J., Schreiber, J., Hannett, N., Kanin, E., Volkert, T.L., Wilson, C.J., Bell, S.P., Young, R.A. Science (2000) [Pubmed]
  6. Elements of the yeast pheromone response pathway required for filamentous growth of diploids. Liu, H., Styles, C.A., Fink, G.R. Science (1993) [Pubmed]
  7. Overexpression of the STE4 gene leads to mating response in haploid Saccharomyces cerevisiae. Whiteway, M., Hougan, L., Thomas, D.Y. Mol. Cell. Biol. (1990) [Pubmed]
  8. 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]
  9. Defects in protein glycosylation cause SHO1-dependent activation of a STE12 signaling pathway in yeast. Cullen, P.J., Schultz, J., Horecka, J., Stevenson, B.J., Jigami, Y., Sprague, G.F. Genetics (2000) [Pubmed]
  10. A novel MAP-kinase kinase from Candida albicans. Singh, P., Ghosh, S., Datta, A. Gene (1997) [Pubmed]
  11. Relative contributions of MCM1 and STE12 to transcriptional activation of a- and alpha-specific genes from Saccharomyces cerevisiae. Hwang-Shum, J.J., Hagen, D.C., Jarvis, E.E., Westby, C.A., Sprague, G.F. Mol. Gen. Genet. (1991) [Pubmed]
  12. Identification of Translational Regulation Target Genes during Filamentous Growth in Saccharomyces cerevisiae: Regulatory Role of Caf20 and Dhh1. Park, Y.U., Hur, H., Ka, M., Kim, J. Eukaryotic Cell (2006) [Pubmed]
  13. Isolation of suppressor mutants of phosphatidylinositol 3-phosphate 5-kinase deficient cells in Schizosaccharomyces pombe. Onishi, M., Nakamura, Y., Koga, T., Takegawa, K., Fukui, Y. Biosci. Biotechnol. Biochem. (2003) [Pubmed]
  14. 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]
  15. A STE12 homolog is required for mating but dispensable for filamentation in candida lusitaniae. Young, L.Y., Lorenz, M.C., Heitman, J. Genetics (2000) [Pubmed]
  16. Identification of a putative transcription factor in Candida albicans that can complement the mating defect of Saccharomyces cerevisiae ste12 mutants. Malathi, K., Ganesan, K., Datta, A. J. Biol. Chem. (1994) [Pubmed]
  17. Aspergillus SteA (sterile12-like) is a homeodomain-C2/H2-Zn+2 finger transcription factor required for sexual reproduction. Vallim, M.A., Miller, K.Y., Miller, B.L. Mol. Microbiol. (2000) [Pubmed]
  18. 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]
  19. A protein domain conserved between yeast MCM1 and human SRF directs ternary complex formation. Mueller, C.G., Nordheim, A. EMBO J. (1991) [Pubmed]
  20. Functional domains of the yeast STE12 protein, a pheromone-responsive transcriptional activator. Kirkman-Correia, C., Stroke, I.L., Fields, S. Mol. Cell. Biol. (1993) [Pubmed]
  21. Transcriptional activation upon pheromone stimulation mediated by a small domain of Saccharomyces cerevisiae Ste12p. Pi, H., Chien, C.T., Fields, S. Mol. Cell. Biol. (1997) [Pubmed]
  22. Repression of yeast Ste12 transcription factor by direct binding of unphosphorylated Kss1 MAPK and its regulation by the Ste7 MEK. Bardwell, L., Cook, J.G., Voora, D., Baggott, D.M., Martinez, A.R., Thorner, J. Genes Dev. (1998) [Pubmed]
  23. Saccharomyces cerevisiae mutants unresponsive to alpha-factor pheromone: alpha-factor binding and extragenic suppression. Jenness, D.D., Goldman, B.S., Hartwell, L.H. Mol. Cell. Biol. (1987) [Pubmed]
  24. 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]
  25. Crosstalk between the Ras2p-controlled mitogen-activated protein kinase and cAMP pathways during invasive growth of Saccharomyces cerevisiae. Mösch, H.U., Kübler, E., Krappmann, S., Fink, G.R., Braus, G.H. Mol. Biol. Cell (1999) [Pubmed]
  26. MAP kinase and cAMP filamentation signaling pathways converge on the unusually large promoter of the yeast FLO11 gene. Rupp, S., Summers, E., Lo, H.J., Madhani, H., Fink, G. EMBO J. (1999) [Pubmed]
  27. Ste12 and Mcm1 regulate cell cycle-dependent transcription of FAR1. Oehlen, L.J., McKinney, J.D., Cross, F.R. Mol. Cell. Biol. (1996) [Pubmed]
  28. Kar4p, a karyogamy-specific component of the yeast pheromone response pathway. Kurihara, L.J., Stewart, B.G., Gammie, A.E., Rose, M.D. Mol. Cell. Biol. (1996) [Pubmed]
  29. Pheromone-dependent phosphorylation of the yeast STE12 protein correlates with transcriptional activation. Song, D., Dolan, J.W., Yuan, Y.L., Fields, S. Genes Dev. (1991) [Pubmed]
  30. The STE12alpha homolog is required for haploid filamentation but largely dispensable for mating and virulence in Cryptococcus neoformans. Yue, C., Cavallo, L.M., Alspaugh, J.A., Wang, P., Cox, G.M., Perfect, J.R., Heitman, J. Genetics (1999) [Pubmed]
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