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. 1992 Jun;11(6):2357–2364. doi: 10.1002/j.1460-2075.1992.tb05295.x

Hsp104 is required for tolerance to many forms of stress.

Y Sanchez 1, J Taulien 1, K A Borkovich 1, S Lindquist 1
PMCID: PMC556703  PMID: 1600951

Abstract

Heat-shock proteins (hsps) are induced by many types of stress. In Saccharomyces cerevisiae, a mutation in the HSP104 gene, a member of the highly conserved hsp100 gene family, reduces the ability of log-phase fermenting cells to withstand high temperatures after mild, conditioning pretreatments. Here, we examine the expression of hsp104 and its importance for survival under many different conditions. Hsp104 is expressed at a higher level in respiring cells than in fermenting cells and is required for the unusually high basal thermotolerance of respiring cells. Its expression in stationary phase cells and spores is crucial for the naturally high thermotolerance of these cell types and for their long-term viability at low temperatures. The protein is of critical importance in tolerance to ethanol and of moderate importance in tolerance to sodium arsenite. Thus, the hsp104 mutation establishes the validity of a long-standing hypothesis in the heat-shock field, namely, that hsps have broadly protective functions. Further, that a single protein is responsible for tolerance to heat, ethanol, arsenite and long-term storage in the cold indicates that the underlying causes of lethality are similar in an extraordinary variety of circumstances. Finally, the protein is of little or no importance in tolerance to copper and cadmium, suggesting that the lethal lesions produced by these agents are fundamentally different from those produced by heat.

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Selected References

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  1. Aujame L., Firko H. The major inducible heat shock protein hsp68 is not required for acquisition of thermal resistance in mouse plasmacytoma cell lines. Mol Cell Biol. 1988 Dec;8(12):5486–5494. doi: 10.1128/mcb.8.12.5486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aust S. D., Morehouse L. A., Thomas C. E. Role of metals in oxygen radical reactions. J Free Radic Biol Med. 1985;1(1):3–25. doi: 10.1016/0748-5514(85)90025-x. [DOI] [PubMed] [Google Scholar]
  3. Barnes C. A., Johnston G. C., Singer R. A. Thermotolerance is independent of induction of the full spectrum of heat shock proteins and of cell cycle blockage in the yeast Saccharomyces cerevisiae. J Bacteriol. 1990 Aug;172(8):4352–4358. doi: 10.1128/jb.172.8.4352-4358.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Borkovich K. A., Farrelly F. W., Finkelstein D. B., Taulien J., Lindquist S. hsp82 is an essential protein that is required in higher concentrations for growth of cells at higher temperatures. Mol Cell Biol. 1989 Sep;9(9):3919–3930. doi: 10.1128/mcb.9.9.3919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carper S. W., Duffy J. J., Gerner E. W. Heat shock proteins in thermotolerance and other cellular processes. Cancer Res. 1987 Oct 15;47(20):5249–5255. [PubMed] [Google Scholar]
  6. Chang E. C., Kosman D. J., Willsky G. R. Arsenic oxide-induced thermotolerance in Saccharomyces cerevisiae. J Bacteriol. 1989 Nov;171(11):6349–6352. doi: 10.1128/jb.171.11.6349-6352.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Craig E. A., Gross C. A. Is hsp70 the cellular thermometer? Trends Biochem Sci. 1991 Apr;16(4):135–140. doi: 10.1016/0968-0004(91)90055-z. [DOI] [PubMed] [Google Scholar]
  8. Craig E. A., Jacobsen K. Mutations of the heat inducible 70 kilodalton genes of yeast confer temperature sensitive growth. Cell. 1984 Oct;38(3):841–849. doi: 10.1016/0092-8674(84)90279-4. [DOI] [PubMed] [Google Scholar]
  9. Esposito R. E., Dresser M., Breitenbach M. Identifying sporulation genes, visualizing synaptonemal complexes, and large-scale spore and spore wall purification. Methods Enzymol. 1991;194:110–131. doi: 10.1016/0076-6879(91)94010-a. [DOI] [PubMed] [Google Scholar]
  10. Goldstein S., Czapski G. The role and mechanism of metal ions and their complexes in enhancing damage in biological systems or in protecting these systems from the toxicity of O2-. J Free Radic Biol Med. 1986;2(1):3–11. doi: 10.1016/0748-5514(86)90117-0. [DOI] [PubMed] [Google Scholar]
  11. Gottesman S., Squires C., Pichersky E., Carrington M., Hobbs M., Mattick J. S., Dalrymple B., Kuramitsu H., Shiroza T., Foster T. Conservation of the regulatory subunit for the Clp ATP-dependent protease in prokaryotes and eukaryotes. Proc Natl Acad Sci U S A. 1990 May;87(9):3513–3517. doi: 10.1073/pnas.87.9.3513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Guy C. L., Plesofsky-Vig N., Brambl R. Heat shock protects germinating conidiospores of Neurospora crassa against freezing injury. J Bacteriol. 1986 Jul;167(1):124–129. doi: 10.1128/jb.167.1.124-129.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hahn G. M., Li G. C. Thermotolerance and heat shock proteins in mammalian cells. Radiat Res. 1982 Dec;92(3):452–457. [PubMed] [Google Scholar]
  14. Hall B. G. Yeast thermotolerance does not require protein synthesis. J Bacteriol. 1983 Dec;156(3):1363–1365. doi: 10.1128/jb.156.3.1363-1365.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hallberg R. L., Kraus K. W., Hallberg E. M. Induction of acquired thermotolerance in Tetrahymena thermophila: effects of protein synthesis inhibitors. Mol Cell Biol. 1985 Aug;5(8):2061–2069. doi: 10.1128/mcb.5.8.2061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hightower L. E. Cultured animal cells exposed to amino acid analogues or puromycin rapidly synthesize several polypeptides. J Cell Physiol. 1980 Mar;102(3):407–427. doi: 10.1002/jcp.1041020315. [DOI] [PubMed] [Google Scholar]
  17. Kurtz S., Rossi J., Petko L., Lindquist S. An ancient developmental induction: heat-shock proteins induced in sporulation and oogenesis. Science. 1986 Mar 7;231(4742):1154–1157. doi: 10.1126/science.3511530. [DOI] [PubMed] [Google Scholar]
  18. Käppeli O. Regulation of carbon metabolism in Saccharomyces cerevisiae and related yeasts. Adv Microb Physiol. 1986;28:181–209. doi: 10.1016/s0065-2911(08)60239-8. [DOI] [PubMed] [Google Scholar]
  19. Lagunas R. Misconceptions about the energy metabolism of Saccharomyces cerevisiae. Yeast. 1986 Dec;2(4):221–228. doi: 10.1002/yea.320020403. [DOI] [PubMed] [Google Scholar]
  20. Laszlo A. Evidence for two states of thermotolerance in mammalian cells. Int J Hyperthermia. 1988 Sep-Oct;4(5):513–526. doi: 10.3109/02656738809027695. [DOI] [PubMed] [Google Scholar]
  21. Li G. C., Li L. G., Liu Y. K., Mak J. Y., Chen L. L., Lee W. M. Thermal response of rat fibroblasts stably transfected with the human 70-kDa heat shock protein-encoding gene. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1681–1685. doi: 10.1073/pnas.88.5.1681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lindquist S., Craig E. A. The heat-shock proteins. Annu Rev Genet. 1988;22:631–677. doi: 10.1146/annurev.ge.22.120188.003215. [DOI] [PubMed] [Google Scholar]
  23. Lindquist S. The heat-shock response. Annu Rev Biochem. 1986;55:1151–1191. doi: 10.1146/annurev.bi.55.070186.005443. [DOI] [PubMed] [Google Scholar]
  24. Parsell D. A., Sanchez Y., Stitzel J. D., Lindquist S. Hsp104 is a highly conserved protein with two essential nucleotide-binding sites. Nature. 1991 Sep 19;353(6341):270–273. doi: 10.1038/353270a0. [DOI] [PubMed] [Google Scholar]
  25. Pelham H. R. Speculations on the functions of the major heat shock and glucose-regulated proteins. Cell. 1986 Sep 26;46(7):959–961. doi: 10.1016/0092-8674(86)90693-8. [DOI] [PubMed] [Google Scholar]
  26. Petko L., Lindquist S. Hsp26 is not required for growth at high temperatures, nor for thermotolerance, spore development, or germination. Cell. 1986 Jun 20;45(6):885–894. doi: 10.1016/0092-8674(86)90563-5. [DOI] [PubMed] [Google Scholar]
  27. Plesset J., Ludwig J. R., Cox B. S., McLaughlin C. S. Effect of cell cycle position on thermotolerance in Saccharomyces cerevisiae. J Bacteriol. 1987 Feb;169(2):779–784. doi: 10.1128/jb.169.2.779-784.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Plesset J., Palm C., McLaughlin C. S. Induction of heat shock proteins and thermotolerance by ethanol in Saccharomyces cerevisiae. Biochem Biophys Res Commun. 1982 Oct 15;108(3):1340–1345. doi: 10.1016/0006-291x(82)92147-7. [DOI] [PubMed] [Google Scholar]
  29. Riabowol K. T., Mizzen L. A., Welch W. J. Heat shock is lethal to fibroblasts microinjected with antibodies against hsp70. Science. 1988 Oct 21;242(4877):433–436. doi: 10.1126/science.3175665. [DOI] [PubMed] [Google Scholar]
  30. Rothman J. E. Polypeptide chain binding proteins: catalysts of protein folding and related processes in cells. Cell. 1989 Nov 17;59(4):591–601. doi: 10.1016/0092-8674(89)90005-6. [DOI] [PubMed] [Google Scholar]
  31. Sanchez Y., Lindquist S. L. HSP104 required for induced thermotolerance. Science. 1990 Jun 1;248(4959):1112–1115. doi: 10.1126/science.2188365. [DOI] [PubMed] [Google Scholar]
  32. Schenberg-Frascino A., Moustacchi E. Lethal and mutagenic effects of elevated temperature on haploid yeast. I. Variations in sensitivity during the cell cycle. Mol Gen Genet. 1972;115(3):243–257. doi: 10.1007/BF00268888. [DOI] [PubMed] [Google Scholar]
  33. Skowyra D., Georgopoulos C., Zylicz M. The E. coli dnaK gene product, the hsp70 homolog, can reactivate heat-inactivated RNA polymerase in an ATP hydrolysis-dependent manner. Cell. 1990 Sep 7;62(5):939–944. doi: 10.1016/0092-8674(90)90268-j. [DOI] [PubMed] [Google Scholar]
  34. Solomon J. M., Rossi J. M., Golic K., McGarry T., Lindquist S. Changes in hsp70 alter thermotolerance and heat-shock regulation in Drosophila. New Biol. 1991 Nov;3(11):1106–1120. [PubMed] [Google Scholar]
  35. Squires C. L., Pedersen S., Ross B. M., Squires C. ClpB is the Escherichia coli heat shock protein F84.1. J Bacteriol. 1991 Jul;173(14):4254–4262. doi: 10.1128/jb.173.14.4254-4262.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Stadtman E. R. Metal ion-catalyzed oxidation of proteins: biochemical mechanism and biological consequences. Free Radic Biol Med. 1990;9(4):315–325. doi: 10.1016/0891-5849(90)90006-5. [DOI] [PubMed] [Google Scholar]
  37. Watson K., Dunlop G., Cavicchioli R. Mitochondrial and cytoplasmic protein syntheses are not required for heat shock acquisition of ethanol and thermotolerance in yeast. FEBS Lett. 1984 Jul 9;172(2):299–302. doi: 10.1016/0014-5793(84)81145-x. [DOI] [PubMed] [Google Scholar]
  38. Watson K. Microbial stress proteins. Adv Microb Physiol. 1990;31:183–223. doi: 10.1016/s0065-2911(08)60122-8. [DOI] [PubMed] [Google Scholar]
  39. Werner-Washburne M., Becker J., Kosic-Smithers J., Craig E. A. Yeast Hsp70 RNA levels vary in response to the physiological status of the cell. J Bacteriol. 1989 May;171(5):2680–2688. doi: 10.1128/jb.171.5.2680-2688.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Widelitz R. B., Magun B. E., Gerner E. W. Effects of cycloheximide on thermotolerance expression, heat shock protein synthesis, and heat shock protein mRNA accumulation in rat fibroblasts. Mol Cell Biol. 1986 Apr;6(4):1088–1094. doi: 10.1128/mcb.6.4.1088. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Yost H. J., Lindquist S. Heat shock proteins affect RNA processing during the heat shock response of Saccharomyces cerevisiae. Mol Cell Biol. 1991 Feb;11(2):1062–1068. doi: 10.1128/mcb.11.2.1062. [DOI] [PMC free article] [PubMed] [Google Scholar]

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