Molecular Genetics and Genomics

, Volume 272, Issue 3, pp 353–362

Heat shock-induced degradation of Msn2p, a Saccharomyces cerevisiae transcription factor, occurs in the nucleus

  • S. Lallet
  • H. Garreau
  • C. Poisier
  • E. Boy-Marcotte
  • M. Jacquet
Original Paper

Abstract

In the yeast Saccharomyces cerevisiae, the zinc finger transcription factor Msn2p is a central component of the general stress response. It is activated in response to a wide variety of environmental changes, including physicochemical stresses as well as nutritional starvation, and induces the expression of a large set of genes required for cellular adaptation. The transcriptional activity of Msn2p in response to stresses is transient, and must therefore be strictly controlled. It is mainly regulated by reversible translocation from the cytoplasm to the nucleus upon the onset of stress, under the control of the cAMP-APK and the TOR pathways. In this report, we describe a new level of control: heat shock-induced degradation of Msn2p by the 26S proteasome. This degradation occurs in the nucleus and is further enhanced when Msn2p is fully active. Moreover, we show that the cyclin-dependent protein kinase Srb10p, a component of the transcription machinery, plays a role in the enhanced degradation of Msn2p upon heat shock. These findings provide new insights into the mechanisms by which Msn2p is transiently activated in response to stress.

Keywords

Stress Msn2p Nuclear degradation Srb10p 

References

  1. Beck T, Hall MN (1999) The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors. Nature 402:689–692CrossRefPubMedGoogle Scholar
  2. Boy-Marcotte E, Tadi D, Perrot M, Boucherie H, Jacquet M (1996) High cAMP levels antagonize the reprogramming of gene expression that occurs at the diauxic shift in Saccharomyces cerevisiae. Microbiology 142:459–467PubMedGoogle Scholar
  3. Boy-Marcotte E, Perrot M, Bussereau F, Boucherie H, Jacquet M (1998) Msn2p and Msn4p control a large number of genes induced at the diauxic transition which are repressed by cyclic AMP in Saccharomyces cerevisiae. J Bacteriol 180:1044–1052PubMedGoogle Scholar
  4. Boy-Marcotte E, Lagniel G, Perrot M, Bussereau F, Boudsocq A, Jacquet M, Labarre J (1999) The heat shock response in yeast: differential regulations and contributions of the Msn2p/Msn4p and Hsf1p regulons. Mol Microbiol 33:274–283CrossRefPubMedGoogle Scholar
  5. Broek D, Toda T, Michaeli T, Levin L, Birchmeier C, Zoller M, Powers S, Wigler M (1987) The S. cerevisiae CDC25 gene product regulates the RAS/adenylate cyclase pathway. Cell 48:789–799CrossRefPubMedGoogle Scholar
  6. Causton HC, Ren B, Koh SS, Harbison CT, Kanin E, Jennings EG, Lee TI, True HL, Lander ES, Young RA (2001) Remodeling of yeast genome expression in response to environmental changes. Mol Biol Cell 12:323–337PubMedGoogle Scholar
  7. Chi Y, Huddleston MJ, Zhang X, Young RA, Annan RS, Carr SA, Deshaies RJ (2001) Negative regulation of Gcn4 and Msn2 transcription factors by Srb10 cyclin-dependent kinase. Genes Dev 15:1078–1092CrossRefPubMedGoogle Scholar
  8. Cooper KF, Mallory MJ, Smith JB, Strich R (1997) Stress and developmental regulation of the yeast C-type cyclin Ume3p (Srb11p/Ssn8p). EMBO J 16:4665–4675CrossRefPubMedGoogle Scholar
  9. Cooper KF, Mallory MJ, Strich R (1999) Oxidative stress-induced destruction of the yeast C-type cyclin Ume3p requires phosphatidylinositol-specific phospholipase C and the 26S proteasome. Mol Cell Biol 19:3338–3348PubMedGoogle Scholar
  10. Estruch F (2000) Stress-controlled transcription factors, stress-induced genes and stress tolerance in budding yeast. FEMS Microbiol Rev 24:469–486CrossRefPubMedGoogle Scholar
  11. Garreau H, Hasan RN, Renault G, Estruch F, Boy-Marcotte E, Jacquet M (2000) Hyperphosphorylation of Msn2p and Msn4p in response to heat shock and the diauxic shift is inhibited by cAMP in Saccharomyces cerevisiae. Microbiology 146:2113–2120PubMedGoogle Scholar
  12. Garrett S, Menold MM, Broach JR (1991) The Saccharomyces cerevisiae YAK1 gene encodes a protein kinase that is induced by arrest early in the cell cycle. Mol Cell Biol 11:4045–4052PubMedGoogle Scholar
  13. Gasch AP, Spellman PT, Kao CM, Carmel-Harel O, Eisen MB, Storz G, Botstein D, Brown PO (2000) Genomic expression programs in the response of yeast cells to environmental changes. Mol Biol Cell 11:4241–4257PubMedGoogle Scholar
  14. Ghaemmaghami S, Huh WK, Bower K, Howson RW, Belle A, Dephoure N, O’Shea EK, Weissman JS (2003) Global analysis of protein expression in yeast. Nature 425:737–741CrossRefPubMedGoogle Scholar
  15. Gorner W, Durchschlag E, Martinez-Pastor MT, Estruch F, Ammerer G, Hamilton B, Ruis H, Schuller C (1998) Nuclear localization of the C2H2 zinc finger protein Msn2p is regulated by stress and protein kinase A activity. Genes Dev 12:586–597PubMedGoogle Scholar
  16. Gorner W, Durchschlag E, Wolf J, Brown EL, Ammerer G, Ruis H, Schuller C (2002) Acute glucose starvation activates the nuclear localization signal of a stress-specific yeast transcription factor. EMBO J 21:135-144CrossRefPubMedGoogle Scholar
  17. Hasan R, Leroy C, Isnard AD, Labarre J, Boy-Marcotte E, Toledano MB (2002) The control of the yeast H2O2 response by the Msn2/4 transcription factors. Mol Microbiol 45:233–241CrossRefPubMedGoogle Scholar
  18. Heinemeyer W, Kleinschmidt JA, Saidowsky J, Escher C, Wolf DH (1991) Proteinase YscE, the yeast proteasome/multicatalytic-multifunctional proteinase: mutants unravel its function in stress induced proteolysis and uncover its necessity for cell survival. EMBO J 10:555–562PubMedGoogle Scholar
  19. Heinemeyer W, Gruhler A, Mohrle V, Mahe Y, Wolf DH (1993) PRE2, highly homologous to the human major histocompatibility complex-linked RING10 gene, codes for a yeast proteasome subunit necessary for chrymotryptic activity and degradation of ubiquitinated proteins. J Biol Chem 268:5115–5120PubMedGoogle Scholar
  20. Hilt W, Wolf DH (1996) Proteasomes: destruction as a programme. Trends Biochem Sci 21:96–102CrossRefPubMedGoogle Scholar
  21. Holstege FC, Jennings EG, Wyrick JJ, Lee TI, Hengartner CJ, Green MR, Golub TR, Lander ES, Young RA (1998) Dissecting the regulatory circuitry of a eukaryotic genome. Cell 95:717–728CrossRefPubMedGoogle Scholar
  22. Jacquet M, Renault G, Lallet S, De Mey J, Goldbeter A (2003a) Oscillatory behavior of the nuclear localization of the transcription factors Msn2 and Msn4 in response to stress in yeast. Scientific World J 3:609–612Google Scholar
  23. Jacquet M, Renault G, Lallet S, De Mey J, Goldbeter A (2003b) Oscillatory nucleocytoplasmic shuttling of the general stress response transcriptional activators Msn2 and Msn4 in Saccharomyces cerevisiae. J Cell Biol 161:497–505CrossRefPubMedGoogle Scholar
  24. Kim TK, Maniatis T (1996) Regulation of interferon-gamma-activated STAT1 by the ubiquitin-proteasome pathway. Science 273:1717–1719Google Scholar
  25. Kyhse-Andersen J (1984) Electroblotting of multiple gels: a simple apparatus without buffer tank for rapid transfer of proteins from polyacrylamide to nitrocellulose. J Biochem Biophys Methods 10:203–209CrossRefPubMedGoogle Scholar
  26. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685PubMedGoogle Scholar
  27. Lenssen E, Oberholzer U, Labarre J, De Virgilio C, Collart MA (2002) Saccharomyces cerevisiae Ccr4-Not complex contributes to the control of Msn2p-dependent transcription by the Ras/cAMP pathway. Mol Microbiol 43:1023–1037CrossRefPubMedGoogle Scholar
  28. Lo RS, Massague J (1999) Ubiquitin-dependent degradation of TGF-beta-activated Smad2. Nat Cell Biol 1:472–478CrossRefPubMedGoogle Scholar
  29. Longtine MS, McKenzie A, Demarini DJ, Shah NG, Wach A, Brachat A, Philippsen P, Pringle JR (1998) Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast 14:953–961CrossRefPubMedGoogle Scholar
  30. Martinez-Pastor MT, Marchler G, Schuller C, Marchler-Bauer A, Ruis H, Estruch F (1996) The Saccharomyces cerevisiae zinc finger proteins Msn2p and Msn4p are required for transcriptional induction through the stress response element (STRE). EMBO J 15:2227–2235PubMedGoogle Scholar
  31. Moskvina E, Schuller C, Maurer CT, Mager WH, Ruis H (1998) A search in the genome of Saccharomyces cerevisiae for genes regulated via stress response elements. Yeast 14:1041–1050CrossRefPubMedGoogle Scholar
  32. Nelson C, Goto S, Lund K, Hung W, Sadowski I (2003) Srb10/Cdk8 regulates yeast filamentous growth by phosphorylating the transcription factor Ste12. Nature 421:187–190CrossRefPubMedGoogle Scholar
  33. Smith A, Ward MP, Garrett S (1998) Yeast PKA represses Msn2p/Msn4p-dependent gene expression to regulate growth, stress response and glycogen accumulation. EMBO J 17:3556–3564CrossRefPubMedGoogle Scholar
  34. Tansey WP (2001) Transcriptional activation: risky business. Genes Dev 15:1045–1050CrossRefPubMedGoogle Scholar
  35. Van Den Hazel HB, Kielland-Brandt MC, Winther JR (1996) Biosynthesis and function of yeast vacuolar proteases. Yeast 12:1–16CrossRefPubMedGoogle Scholar
  36. Volland C, Garnier C, Haguenauer-Tsapis R (1992) In vivo phosphorylation of the yeast uracil permease. J Biol Chem 267:23767–23771PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • S. Lallet
    • 1
  • H. Garreau
    • 1
  • C. Poisier
    • 1
  • E. Boy-Marcotte
    • 1
  • M. Jacquet
    • 1
  1. 1.Laboratoire Information Génétique et Développement, Institut de Génétique et Microbiologie, UMR CNRS C8621Université Paris-SudOrsay CedexFrance

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