Search tips
Search criteria 


Logo of jbacterPermissionsJournals.ASM.orgJournalJB ArticleJournal InfoAuthorsReviewers
J Bacteriol. 1993 October; 175(20): 6484–6491.
PMCID: PMC206757

Genetic evidence for a functional relationship between Hsp104 and Hsp70.


The phenotypes of single Hsp104 and Hsp70 mutants of the budding yeast Saccharomyces cerevisiae provide no clue that these proteins are functionally related. Mutation of the HSP104 gene severely reduces the ability of cells to survive short exposures to extreme temperatures (thermotolerance) but has no effect on growth rates. On the other hand, mutations in the genes that encode Hsp70 proteins have significant effects on growth rates but do not reduce thermotolerance. The absence of a thermotolerance defect in S. cerevisiae Hsp70 mutants is puzzling, since the protein clearly plays an important role in thermotolerance in a variety of other organisms. In this report, examination of the phenotypes of combined Hsp104 and Hsp70 mutants uncovers similarities in the functions of Hsp104 and Hsp70 not previously apparent. In the absence of the Hsp104 protein, Hsp70 is very important for thermotolerance in S. cerevisiae, particularly at very early times after a temperature upshift. Similarly, Hsp104 plays a substantial role in vegetative growth under conditions of decreased Hsp70 protein levels. These results suggest a close functional relationship between Hsp104 and Hsp70.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.9M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Craig EA. Essential roles of 70kDa heat inducible proteins. Bioessays. 1989 Aug-Sep;11(2-3):48–52. [PubMed]
  • Craig EA, Jacobsen K. Mutations of the heat inducible 70 kilodalton genes of yeast confer temperature sensitive growth. Cell. 1984 Oct;38(3):841–849. [PubMed]
  • Craig EA, Jacobsen K. Mutations in cognate genes of Saccharomyces cerevisiae hsp70 result in reduced growth rates at low temperatures. Mol Cell Biol. 1985 Dec;5(12):3517–3524. [PMC free article] [PubMed]
  • Daufeldt JA, Harrison HH. Quality control and technical outcome of ISO-DALT two-dimensional electrophoresis in a clinical laboratory setting. Clin Chem. 1984 Dec;30(12 Pt 1):1972–1980. [PubMed]
  • DiDomenico BJ, Bugaisky GE, Lindquist S. The heat shock response is self-regulated at both the transcriptional and posttranscriptional levels. Cell. 1982 Dec;31(3 Pt 2):593–603. [PubMed]
  • Feder JH, Rossi JM, Solomon J, Solomon N, Lindquist S. The consequences of expressing hsp70 in Drosophila cells at normal temperatures. Genes Dev. 1992 Aug;6(8):1402–1413. [PubMed]
  • Flynn GC, Chappell TG, Rothman JE. Peptide binding and release by proteins implicated as catalysts of protein assembly. Science. 1989 Jul 28;245(4916):385–390. [PubMed]
  • Flynn GC, Pohl J, Flocco MT, Rothman JE. Peptide-binding specificity of the molecular chaperone BiP. Nature. 1991 Oct 24;353(6346):726–730. [PubMed]
  • Gottesman S, Squires C, Pichersky E, Carrington M, Hobbs M, Mattick JS, Dalrymple B, Kuramitsu H, Shiroza T, Foster T, et al. 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. [PubMed]
  • Hartl FU, Martin J, Neupert W. Protein folding in the cell: the role of molecular chaperones Hsp70 and Hsp60. Annu Rev Biophys Biomol Struct. 1992;21:293–322. [PubMed]
  • Hwang BJ, Woo KM, Goldberg AL, Chung CH. Protease Ti, a new ATP-dependent protease in Escherichia coli, contains protein-activated ATPase and proteolytic functions in distinct subunits. J Biol Chem. 1988 Jun 25;263(18):8727–8734. [PubMed]
  • Katayama Y, Gottesman S, Pumphrey J, Rudikoff S, Clark WP, Maurizi MR. The two-component, ATP-dependent Clp protease of Escherichia coli. Purification, cloning, and mutational analysis of the ATP-binding component. J Biol Chem. 1988 Oct 15;263(29):15226–15236. [PubMed]
  • Landry J, Chrétien P, Lambert H, Hickey E, Weber LA. Heat shock resistance conferred by expression of the human HSP27 gene in rodent cells. J Cell Biol. 1989 Jul;109(1):7–15. [PMC free article] [PubMed]
  • Landry SJ, Jordan R, McMacken R, Gierasch LM. Different conformations for the same polypeptide bound to chaperones DnaK and GroEL. Nature. 1992 Jan 30;355(6359):455–457. [PubMed]
  • Lewis MJ, Pelham HR. Involvement of ATP in the nuclear and nucleolar functions of the 70 kd heat shock protein. EMBO J. 1985 Dec 1;4(12):3137–3143. [PubMed]
  • Li GC, Li LG, Liu YK, Mak JY, Chen LL, Lee WM. 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. [PubMed]
  • Lindquist S, Craig EA. The heat-shock proteins. Annu Rev Genet. 1988;22:631–677. [PubMed]
  • Parsell DA, Sanchez Y, Stitzel JD, Lindquist S. Hsp104 is a highly conserved protein with two essential nucleotide-binding sites. Nature. 1991 Sep 19;353(6341):270–273. [PubMed]
  • Parsell DA, Taulien J, Lindquist S. The role of heat-shock proteins in thermotolerance. Philos Trans R Soc Lond B Biol Sci. 1993 Mar 29;339(1289):279–286. [PubMed]
  • Pelham HR. Speculations on the functions of the major heat shock and glucose-regulated proteins. Cell. 1986 Sep 26;46(7):959–961. [PubMed]
  • 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. [PubMed]
  • Riabowol KT, Mizzen LA, Welch WJ. Heat shock is lethal to fibroblasts microinjected with antibodies against hsp70. Science. 1988 Oct 21;242(4877):433–436. [PubMed]
  • Sanchez Y, Lindquist SL. HSP104 required for induced thermotolerance. Science. 1990 Jun 1;248(4959):1112–1115. [PubMed]
  • Sanchez Y, Taulien J, Borkovich KA, Lindquist S. Hsp104 is required for tolerance to many forms of stress. EMBO J. 1992 Jun;11(6):2357–2364. [PubMed]
  • 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. [PubMed]
  • Solomon JM, Rossi JM, 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]
  • Stone DE, Craig EA. Self-regulation of 70-kilodalton heat shock proteins in Saccharomyces cerevisiae. Mol Cell Biol. 1990 Apr;10(4):1622–1632. [PMC free article] [PubMed]
  • Straus D, Walter W, Gross CA. DnaK, DnaJ, and GrpE heat shock proteins negatively regulate heat shock gene expression by controlling the synthesis and stability of sigma 32. Genes Dev. 1990 Dec;4(12A):2202–2209. [PubMed]
  • Tilly K, McKittrick N, Zylicz M, Georgopoulos C. The dnaK protein modulates the heat-shock response of Escherichia coli. Cell. 1983 Sep;34(2):641–646. [PubMed]
  • Werner-Washburne M, Becker J, Kosic-Smithers J, Craig EA. Yeast Hsp70 RNA levels vary in response to the physiological status of the cell. J Bacteriol. 1989 May;171(5):2680–2688. [PMC free article] [PubMed]
  • Werner-Washburne M, Craig EA. Expression of members of the Saccharomyces cerevisiae hsp70 multigene family. Genome. 1989;31(2):684–689. [PubMed]
  • Werner-Washburne M, Stone DE, Craig EA. Complex interactions among members of an essential subfamily of hsp70 genes in Saccharomyces cerevisiae. Mol Cell Biol. 1987 Jul;7(7):2568–2577. [PMC free article] [PubMed]
  • Yost HJ, Petersen RB, Lindquist S. RNA metabolism: strategies for regulation in the heat shock response. Trends Genet. 1990 Jul;6(7):223–227. [PubMed]

Articles from Journal of Bacteriology are provided here courtesy of American Society for Microbiology (ASM)