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Gene Review

MSN4  -  Msn4p

Saccharomyces cerevisiae S288c

Synonyms: Multicopy suppressor of SNF1 protein 4, YKL062W, Zinc finger protein MSN4
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High impact information on MSN4

  • TOR inhibits expression of carbon-source-regulated genes by stimulating the binding of the transcriptional activators MSN2 and MSN4 to the cytoplasmic 14-3-3 protein BMH2 [1].
  • Stress-resistance transcription factors Msn2/Msn4 and protein kinase Rim15 were required for this life-span extension [2].
  • Both Msn2p and Msn4p are Cys2His2 zinc finger proteins and bind to the stress response element (STRE) [3].
  • Msn2p and the partially redundant factor Msn4p are key regulators of stress-responsive gene expression in Saccharomyces cerevisiae [3].
  • We show by time-course studies that transcriptional induction of the yeast glucose-regulated SUC2 gene is rapid and shows a striking biphasic pattern, the first phase of which is partly mediated by the general stress transcription factors Msn2p/Msn4p [4].

Biological context of MSN4


Associations of MSN4 with chemical compounds


Regulatory relationships of MSN4

  • A double mutant of the MSN2 and MSN4 gene was unable to induce expression of the GLO1 gene under highly osmotic conditions [11].
  • Disruption of MSN2 and MSN4 abolishes or significantly reduces the heat- and NaCl-induced increases in Nth1 activity and transcription [7].
  • The Hog1p is one of the mitogen-activated protein kinases (MAPKs) in S. cerevisiae, and both Msn2p and Msn4p are the transcriptional regulators that are thought to be under the control of Hog1p-MAPK [11].
  • In addition, GRE1 and GRE3 are regulated negatively by the cAMP-PKA transduction pathway and positively by the transcriptional factors Msn2p and Msn4p [12].
  • In addition to two Yap1p response elements (YREs), TTACTAA and TTAGTAA, the presence of two stress response elements (STREs) (CCCCT) in the upstream sequence of cTPx II also suggests that Msn2p/Msn4p could control stress-induced expression of cTPx II [13].

Other interactions of MSN4

  • Our results suggest that MSN2 and MSN4 encode a DNA-binding component of the stress responsive system and it is likely that they act as positive transcription factors [5].
  • However, the triple deletion of stress-resistance genes MSN2/MSN4 and RIM15, which causes a major decrease in chronological life span, extends replicative life span [14].
  • Induction of neutral trehalase Nth1 by heat and osmotic stress is controlled by STRE elements and Msn2/Msn4 transcription factors: variations of PKA effect during stress and growth [7].
  • Significantly, yeast adaptation to 2,4-D involves the rapid and transient Msn2p- and Msn4p-mediated activation (fivefold) of SPI1 transcription [8].
  • Among them, the heat shock factor (Hsf1p) and the zinc finger proteins of the general stress response (Msn2p and Msn4p) have been shown to play a major role in stress protection [15].

Analytical, diagnostic and therapeutic context of MSN4

  • Here we show by immunoblotting experiments that Msn2p and Msn4p are phosphorylated in vivo during growth on glucose, and become hyperphosphorylated at the diauxic transition and upon heat shock [16].


  1. The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors. Beck, T., Hall, M.N. Nature (1999) [Pubmed]
  2. Regulation of longevity and stress resistance by Sch9 in yeast. Fabrizio, P., Pozza, F., Pletcher, S.D., Gendron, C.M., Longo, V.D. Science (2001) [Pubmed]
  3. Nuclear localization of the C2H2 zinc finger protein Msn2p is regulated by stress and protein kinase A activity. Görner, W., Durchschlag, E., Martinez-Pastor, M.T., Estruch, F., Ammerer, G., Hamilton, B., Ruis, H., Schüller, C. Genes Dev. (1998) [Pubmed]
  4. Roles of SWI/SNF and HATs throughout the dynamic transcription of a yeast glucose-repressible gene. Geng, F., Laurent, B.C. EMBO J. (2004) [Pubmed]
  5. The Saccharomyces cerevisiae zinc finger proteins Msn2p and Msn4p are required for transcriptional induction through the stress response element (STRE). Martínez-Pastor, M.T., Marchler, G., Schüller, C., Marchler-Bauer, A., Ruis, H., Estruch, F. EMBO J. (1996) [Pubmed]
  6. Msn2p, a zinc finger DNA-binding protein, is the transcriptional activator of the multistress response in Saccharomyces cerevisiae. Schmitt, A.P., McEntee, K. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  7. Induction of neutral trehalase Nth1 by heat and osmotic stress is controlled by STRE elements and Msn2/Msn4 transcription factors: variations of PKA effect during stress and growth. Zähringer, H., Thevelein, J.M., Nwaka, S. Mol. Microbiol. (2000) [Pubmed]
  8. Adaptation of Saccharomyces cerevisiae to the herbicide 2,4-dichlorophenoxyacetic acid, mediated by Msn2p- and Msn4p-regulated genes: important role of SPI1. Simões, T., Teixeira, M.C., Fernandes, A.R., Sá-Correia, I. Appl. Environ. Microbiol. (2003) [Pubmed]
  9. Msn2p and Msn4p control a large number of genes induced at the diauxic transition which are repressed by cyclic AMP in Saccharomyces cerevisiae. Boy-Marcotte, E., Perrot, M., Bussereau, F., Boucherie, H., Jacquet, M. J. Bacteriol. (1998) [Pubmed]
  10. The transcriptional response of Saccharomyces cerevisiae to osmotic shock. Hot1p and Msn2p/Msn4p are required for the induction of subsets of high osmolarity glycerol pathway-dependent genes. Rep, M., Krantz, M., Thevelein, J.M., Hohmann, S. J. Biol. Chem. (2000) [Pubmed]
  11. Expression of the glyoxalase I gene of Saccharomyces cerevisiae is regulated by high osmolarity glycerol mitogen-activated protein kinase pathway in osmotic stress response. Inoue, Y., Tsujimoto, Y., Kimura, A. J. Biol. Chem. (1998) [Pubmed]
  12. Three genes whose expression is induced by stress in Saccharomyces cerevisiae. Garay-Arroyo, A., Covarrubias, A.A. Yeast (1999) [Pubmed]
  13. Msn2p/Msn4p act as a key transcriptional activator of yeast cytoplasmic thiol peroxidase II. Hong, S.K., Cha, M.K., Choi, Y.S., Kim, W.C., Kim, I.H. J. Biol. Chem. (2002) [Pubmed]
  14. Chronological aging-independent replicative life span regulation by Msn2/Msn4 and Sod2 in Saccharomyces cerevisiae. Fabrizio, P., Pletcher, S.D., Minois, N., Vaupel, J.W., Longo, V.D. FEBS Lett. (2004) [Pubmed]
  15. Hsf1p and Msn2/4p cooperate in the expression of Saccharomyces cerevisiae genes HSP26 and HSP104 in a gene- and stress type-dependent manner. Amorós, M., Estruch, F. Mol. Microbiol. (2001) [Pubmed]
  16. Hyperphosphorylation of Msn2p and Msn4p in response to heat shock and the diauxic shift is inhibited by cAMP in Saccharomyces cerevisiae. Garreau, H., Hasan, R.N., Renault, G., Estruch, F., Boy-Marcotte, E., Jacquet, M. Microbiology (Reading, Engl.) (2000) [Pubmed]
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