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SKN7  -  Skn7p

Saccharomyces cerevisiae S288c

Synonyms: BRY1, POS9, Peroxide sensitivity protein 9, Transcription factor SKN7, YHR206W
 
 
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High impact information on SKN7

  • We show that the overexpression of SKN7, a response-regulator transcription factor, activates transcription from a calcineurin/Crz1p-dependent response element (CDRE) [1].
  • Calcineurin, but not its phosphatase activity, is required for Skn7p-mediated Crz1p stabilization [1].
  • In contrast, we show that Sln1p activation of Skn7p requires phosphorylation of D427 [2].
  • The established role of Skn7p in oxidative stress is independent of the conserved receiver domain aspartate, D427 [2].
  • The yeast histidine protein kinase, Sln1p, mediates phosphotransfer to two response regulators, Ssk1p and Skn7p [2].
 

Biological context of SKN7

 

Anatomical context of SKN7

  • SKN7, a yeast multicopy suppressor of a mutation affecting cell wall beta-glucan assembly, encodes a product with domains homologous to prokaryotic two-component regulators and to heat shock transcription factors [6].
  • By comparing transcript profiles of C. neoformans serotype D B3501 cells recovered from endothelial cells with those from free-grown cryptococci, we identified the cryptococcal homologue of the SKN7 two-component stress response regulator gene from Saccharomyces cerevisiae [7].
  • Our results suggest that the blocking of vesicle transport by a loss of the Trs130p function causes some defect in the cell wall mannoproteins, which leads to the elevated expression of OCH1 through the Skn7p function, to compensate for the defect [8].
  • The Skn7 response regulator of Cryptococcus neoformans is involved in oxidative stress signalling and augments intracellular survival in endothelium [7].
 

Associations of SKN7 with chemical compounds

  • SKN7 did not suppress other mutations in the (1-->6)-beta-glucan biosynthetic pathway, suggesting that SKN7 does not act as a general bypass suppressor of this glucan [6].
  • To isolate new antioxidant genes, we have searched for activities that would rescue the tert-butyl hydroperoxide (t-BOOH)-hypersensitive phenotype of a Saccharomyces cerevisiae strain deleted for the gene encoding the oxidative stress response regulator Skn7 [9].
  • This lack of induction was specific as the fap7-1 mutant response to other stresses such as sodium chloride or co-application of both hydrogen peroxide and sodium chloride was not affected, as tested with the Pos9-independent expression pattern of a TPS2-lacZ reporter system [10].
  • The correlation between H(2)O(2) sensitivity and the accumulation of oxidized proteins was evaluated by assaying protein carbonyls in mutants deficient in the stress response regulators Yap1p and Skn7p [11].
  • Both, a yap1 and skn7 mutant were highly sensitive to Rose Bengal, an exogenous photosensitizer producing singlet oxygen in the light [12].
 

Physical interactions of SKN7

  • Our studies reveal that the Skn7p HSF-like DNA binding domain interacts with a cis-acting element identified upstream of OCH1 that is distinct from the previously defined HSE-like Skn7p binding site [5].
  • In addition to consensus YRE and OSRE sequences, novel Yap1p and Skn7p binding sites were identified in the CCP1 promoter [13].
  • The DNA-binding domain of Skn7p is also required for binding to Crz1p and calcineurin in vitro [1].
  • The Skn7 response regulator of Saccharomyces cerevisiae interacts with Hsf1 in vivo and is required for the induction of heat shock genes by oxidative stress [14].
 

Regulatory relationships of SKN7

  • Similarly, high overexpression of Mbp1 is lethal and can be suppressed by skn7 mutations [3].
  • Modulation of Sln1 kinase activity in response to changes in the osmotic environment regulates the activity of the osmotic response mitogen-activated protein kinase pathway and the activity of the Skn7p transcription factor, both important for adaptation to changing osmotic stress conditions [15].
  • The SLN1 two-component signaling pathway of Saccharomyces cerevisiae utilizes a multistep phosphorelay mechanism to control osmotic stress responses via the HOG1 mitogen-activated protein kinase pathway and the transcription factor Skn7p [16].
  • The eukaryotic response regulator Skn7p regulates calcineurin signaling through stabilization of Crz1p [1].
 

Other interactions of SKN7

  • Association of the cell cycle transcription factor Mbp1 with the Skn7 response regulator in budding yeast [3].
  • The contribution of Skn7p to HOG pathway regulation appears to be modulated by the receiver domain, since non-phosphorylatable Skn7pD427N is unable to fully restore growth to ptc1/skn7 cells [4].
  • AHP1 exerts strong antioxidant protective functions, as demonstrated both by gene overexpression and deletion analyses, and is inducible by peroxides in an Yap1- and Skn7-dependent manner [9].
  • The eukaryotic two-component histidine kinase Sln1p regulates OCH1 via the transcription factor, Skn7p [5].
  • Our data suggest that Fap7 is a nuclear factor important for Pos9-dependent target gene transcription upon oxidative stress [10].
 

Analytical, diagnostic and therapeutic context of SKN7

References

  1. The eukaryotic response regulator Skn7p regulates calcineurin signaling through stabilization of Crz1p. Williams, K.E., Cyert, M.S. EMBO J. (2001) [Pubmed]
  2. The yeast histidine protein kinase, Sln1p, mediates phosphotransfer to two response regulators, Ssk1p and Skn7p. Li, S., Ault, A., Malone, C.L., Raitt, D., Dean, S., Johnston, L.H., Deschenes, R.J., Fassler, J.S. EMBO J. (1998) [Pubmed]
  3. Association of the cell cycle transcription factor Mbp1 with the Skn7 response regulator in budding yeast. Bouquin, N., Johnson, A.L., Morgan, B.A., Johnston, L.H. Mol. Biol. Cell (1999) [Pubmed]
  4. Yeast Skn7p activity is modulated by the Sln1p-Ypd1p osmosensor and contributes to regulation of the HOG pathway. Ketela, T., Brown, J.L., Stewart, R.C., Bussey, H. Mol. Gen. Genet. (1998) [Pubmed]
  5. The eukaryotic two-component histidine kinase Sln1p regulates OCH1 via the transcription factor, Skn7p. Li, S., Dean, S., Li, Z., Horecka, J., Deschenes, R.J., Fassler, J.S. Mol. Biol. Cell (2002) [Pubmed]
  6. SKN7, a yeast multicopy suppressor of a mutation affecting cell wall beta-glucan assembly, encodes a product with domains homologous to prokaryotic two-component regulators and to heat shock transcription factors. Brown, J.L., North, S., Bussey, H. J. Bacteriol. (1993) [Pubmed]
  7. The Skn7 response regulator of Cryptococcus neoformans is involved in oxidative stress signalling and augments intracellular survival in endothelium. Coenjaerts, F.E., Hoepelman, A.I., Scharringa, J., Aarts, M., Ellerbroek, P.M., Bevaart, L., Van Strijp, J.A., Janbon, G. FEMS Yeast Res. (2006) [Pubmed]
  8. Mutation of TRS130, which encodes a component of the TRAPP II complex, activates transcription of OCH1 in Saccharomyces cerevisiae. Yamamoto, K., Jigami, Y. Curr. Genet. (2002) [Pubmed]
  9. A new antioxidant with alkyl hydroperoxide defense properties in yeast. Lee, J., Spector, D., Godon, C., Labarre, J., Toledano, M.B. J. Biol. Chem. (1999) [Pubmed]
  10. The essential protein fap7 is involved in the oxidative stress response of Saccharomyces cerevisiae. Juhnke, H., Charizanis, C., Latifi, F., Krems, B., Entian, K.D. Mol. Microbiol. (2000) [Pubmed]
  11. Hydrogen peroxide-induced carbonylation of key metabolic enzymes in Saccharomyces cerevisiae: the involvement of the oxidative stress response regulators Yap1 and Skn7. Costa, V.M., Amorim, M.A., Quintanilha, A., Moradas-Ferreira, P. Free Radic. Biol. Med. (2002) [Pubmed]
  12. The role of Yap1p and Skn7p-mediated oxidative stress response in the defence of Saccharomyces cerevisiae against singlet oxygen. Brombacher, K., Fischer, B.B., Rüfenacht, K., Eggen, R.I. Yeast (2006) [Pubmed]
  13. Identification of novel Yap1p and Skn7p binding sites involved in the oxidative stress response of Saccharomyces cerevisiae. He, X.J., Fassler, J.S. Mol. Microbiol. (2005) [Pubmed]
  14. The Skn7 response regulator of Saccharomyces cerevisiae interacts with Hsf1 in vivo and is required for the induction of heat shock genes by oxidative stress. Raitt, D.C., Johnson, A.L., Erkine, A.M., Makino, K., Morgan, B., Gross, D.S., Johnston, L.H. Mol. Biol. Cell (2000) [Pubmed]
  15. Role for the Ran binding protein, Mog1p, in Saccharomyces cerevisiae SLN1-SKN7 signal transduction. Lu, J.M., Deschenes, R.J., Fassler, J.S. Eukaryotic Cell (2004) [Pubmed]
  16. Altered phosphotransfer in an activated mutant of the Saccharomyces cerevisiae two-component osmosensor Sln1p. Ault, A.D., Fassler, J.S., Deschenes, R.J. Eukaryotic Cell (2002) [Pubmed]
  17. Yap1 and Skn7 control two specialized oxidative stress response regulons in yeast. Lee, J., Godon, C., Lagniel, G., Spector, D., Garin, J., Labarre, J., Toledano, M.B. J. Biol. Chem. (1999) [Pubmed]
 
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