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Gene Review

MSN2  -  Msn2p

Saccharomyces cerevisiae S288c

Synonyms: Multicopy suppressor of SNF1 protein 2, YM9532.02C, YMR037C, Zinc finger protein MSN2
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Disease relevance of MSN2


High impact information on MSN2

  • Stress-resistance transcription factors Msn2/Msn4 and protein kinase Rim15 were required for this life-span extension [3].
  • Negative regulation of Gcn4 and Msn2 transcription factors by Srb10 cyclin-dependent kinase [4].
  • Apart from PKA, the protein kinase Snf1 can also directly modify one of the Msn2 phosphorylation sites (S582) and thereby repress Msn2 function [5].
  • A dual role for PP1 in shaping the Msn2-dependent transcriptional response to glucose starvation [5].
  • Msn2 activation by sudden glucose depletion correlates with a fast but transient decrease in phosphorylation of several sites in its nuclear localization signal (NLS) [5].

Biological context of MSN2

  • The MSN2 and MSN4 genes encode homologous and functionally redundant Cys2His2 zinc finger proteins [6].
  • A disruption of both MSN2 and MSN4 genes results in a higher sensitivity to different stresses, including carbon source starvation, heat shock and severe osmotic and oxidative stresses [6].
  • We present evidence that the MSN2 homolog, MSN4, can partially replace MSN2 for transcriptional activation following stress [7].
  • Deletion of MSN2/4, encoding transcription factors driving STRE-dependent gene expression, decreased DUR [8].
  • Furthermore, heat shock induction of a STRE-driven reporter gene was reduced more than 6-fold in the msn2 strain relative to wild-type cells [7].

Anatomical context of MSN2

  • In cells growing in glucose, Msn2 is located mainly in the cytosol, whereas in carbon source-starved cells, Msn2 is located largely inside the nucleus [9].

Associations of MSN2 with chemical compounds


Physical interactions of MSN2


Regulatory relationships of MSN2

  • HSF and Msn2/4p can exclusively or cooperatively activate the yeast HSP104 gene [15].
  • These genes are activated by Msn2 and repressed by the Srb10 kinase, a member of the mediator complex [16].
  • Mutations that decrease the activity of the Ras/Cyr1/PKA pathway also extend longevity and increase stress resistance by activating transcription factors Msn2/Msn4 and the mitochondrial antioxidant enzyme superoxide dismutase (Sod2) [17].
  • The localization defect in these mutants is specific for carbon starvation stress, and it is because of the presence of an abnormally active Snf1 protein kinase that inhibits the nuclear localization of Msn2 upon carbon starvation [9].
  • Similar effects were found in msn5 mutant cells that block Msn2 nuclear export [11].

Other interactions of MSN2

  • 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 [6].
  • However, the contribution of Hsf1, independent of Msn2/4, is only beginning to emerge [18].
  • However, we found that reduction or elimination of PKA activity strongly derepresses transcription of the small heat-shock genes HSP26 and HSP12, even in the absence of MSN2/4 [19].
  • These results indicate that, in addition to trehalose, Hsp104 and the Msn2/4-controlled genes, other factors exist in S. cerevisiae that can, significantly and independently of the known factors, enhance general stress resistance [20].
  • The multicopy suppressors of the snf1 defect, Msn2p and Msn4p transcription factors (Msn2/4p), activate genes through the stress-responsive cis element (CCCCT) in response to various stresses [21].

Analytical, diagnostic and therapeutic context of MSN2

  • Disruption of the MSN2 gene abolished an STRE-binding activity in crude extracts as judged by both gel mobility-shift and Southwestern blot experiments, and overexpression of MSN2 intensified this binding activity [7].
  • We analyzed the two-dimensional gel electrophoresis pattern of protein synthesis of the msn2 msn4 double mutant and compared it with that of the wild-type strain during exponential growth phase and at the diauxic transition [21].


  1. 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]
  2. Two homologous zinc finger genes identified by multicopy suppression in a SNF1 protein kinase mutant of Saccharomyces cerevisiae. Estruch, F., Carlson, M. Mol. Cell. Biol. (1993) [Pubmed]
  3. 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]
  4. Negative regulation of Gcn4 and Msn2 transcription factors by Srb10 cyclin-dependent kinase. Chi, Y., Huddleston, M.J., Zhang, X., Young, R.A., Annan, R.S., Carr, S.A., Deshaies, R.J. Genes Dev. (2001) [Pubmed]
  5. A dual role for PP1 in shaping the Msn2-dependent transcriptional response to glucose starvation. De Wever, V., Reiter, W., Ballarini, A., Ammerer, G., Brocard, C. EMBO J. (2005) [Pubmed]
  6. 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]
  7. 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]
  8. Upregulation of the Hsp104 chaperone at physiological temperature during recovery from thermal insult. Seppä, L., Hänninen, A.L., Makarow, M. Mol. Microbiol. (2004) [Pubmed]
  9. Convergence of the target of rapamycin and the Snf1 protein kinase pathways in the regulation of the subcellular localization of Msn2, a transcriptional activator of STRE (Stress Response Element)-regulated genes. Mayordomo, I., Estruch, F., Sanz, P. J. Biol. Chem. (2002) [Pubmed]
  10. Overexpression of Bop3 confers resistance to methylmercury in Saccharomyces cerevisiae through interaction with other proteins such as Fkh1, Rts1, and Msn2. Hwang, G.W., Furuoya, Y., Hiroshima, A., Furuchi, T., Naganuma, A. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  11. Nuclear localization destabilizes the stress-regulated transcription factor Msn2. Durchschlag, E., Reiter, W., Ammerer, G., Schüller, C. J. Biol. Chem. (2004) [Pubmed]
  12. Very low amounts of glucose cause repression of the stress-responsive gene HSP12 in Saccharomyces cerevisiae. de Groot, E., Bebelman, J.P., Mager, W.H., Planta, R.J. Microbiology (Reading, Engl.) (2000) [Pubmed]
  13. A Peroxisomal Glutathione Transferase of Saccharomyces cerevisiae Is Functionally Related to Sulfur Amino Acid Metabolism. Barreto, L., Garcer??, A., Jansson, K., Sunnerhagen, P., Herrero, E. Eukaryotic Cell (2006) [Pubmed]
  14. Role of Gal11, a component of the RNA polymerase II mediator in stress-induced hyperphosphorylation of Msn2 in Saccharomyces cerevisiae. Lallet, S., Garreau, H., Garmendia-Torres, C., Szestakowska, D., Boy-Marcotte, E., Quevillon-Ch??ruel, S., Jacquet, M. Mol. Microbiol. (2006) [Pubmed]
  15. HSF and Msn2/4p can exclusively or cooperatively activate the yeast HSP104 gene. Grably, M.R., Stanhill, A., Tell, O., Engelberg, D. Mol. Microbiol. (2002) [Pubmed]
  16. Genetic factors that regulate the attenuation of the general stress response of yeast. Bose, S., Dutko, J.A., Zitomer, R.S. Genetics (2005) [Pubmed]
  17. The Ras and Sch9 pathways regulate stress resistance and longevity. Longo, V.D. Exp. Gerontol. (2003) [Pubmed]
  18. Genome-wide Analysis Reveals New Roles for the Activation Domains of the Saccharomyces cerevisiae Heat Shock Transcription Factor (Hsf1) during the Transient Heat Shock Response. Eastmond, D.L., Nelson, H.C. J. Biol. Chem. (2006) [Pubmed]
  19. Protein kinase A regulates constitutive expression of small heat-shock genes in an Msn2/4p-independent and Hsf1p-dependent manner in Saccharomyces cerevisiae. Ferguson, S.B., Anderson, E.S., Harshaw, R.B., Thate, T., Craig, N.L., Nelson, H.C. Genetics (2005) [Pubmed]
  20. The high general stress resistance of the Saccharomyces cerevisiae fil1 adenylate cyclase mutant (Cyr1Lys1682) is only partially dependent on trehalose, Hsp104 and overexpression of Msn2/4-regulated genes. Versele, M., Thevelein, J.M., Van Dijck, P. Yeast (2004) [Pubmed]
  21. 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]
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