Molecular Biology

, Volume 42, Issue 1, pp 110–116

Yeast chaperone Hsp104 controls gene expression at the posttranscriptional level

  • A. A. Rubel
  • A. F. Saifitdinova
  • A. G. Lada
  • A. A. Nizhnikov
  • S. G. Inge-Vechtomov
  • A. P. Galkin
Cell Molecular Biology

Abstract

Yeast chaperone Hsp104 is known as a protein responsible for dissociation of aggregates of heat-damaged proteins and prion aggregates into smaller pieces or monomers. The effects of Hsp104 on PrP-GFP and GFP were analyzed. PrP-GFP forms high-molecular-weight aggregates, whereas GFP is unable to aggregate in yeast cells. Hsp104 proved to regulate the amount of PrP-GFP and GFP in yeast cells, and the direction of chaperone action depended on the promoters controlling the production of these proteins. Overproduction of Hsp104 increased the levels of PrP-GFP and GFP when their genes were controlled by the CUP1 promoter. In contrast, overproduction of Hsp104 decreased the levels of PrP-GFP and GFP in the case of their expression under the control of the GPD promoter. The effects of Hsp104 were not related to any changes in the contents of mRNAs of the genes under investigation nor to the ability of the proteins to form aggregates. Thus, the Hsp104 functions were not confined to dissociation of protein aggregates. Hsp104 was assumed to regulate gene expression at the posttranscriptional level.

Key words

Hsp104 chaperone expression regulation yeast Saccharomyces cerevisiae mammalian prion promoter structure 

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References

  1. 1.
    Parsell D.A., Kowal A.S., Lindquist S. 1994. S. cerevisiae Hsp104 protein. Purification and characterization of ATP-induced structural changes. J. Biol. Chem. 269, 4480–4487.PubMedGoogle Scholar
  2. 2.
    Bosl B., Grimminger V., Walter S. 2006. The molecular chaperone Hsp104: A molecular machine for protein disaggregation. J. Struct. Biol. 156, 139–148.PubMedGoogle Scholar
  3. 3.
    Glover J.R., Lindquist S. 1998. Hsp104, Hsp70, and Hsp40: A novel chaperone system that rescues previously aggregated proteins. Cell. 94, 73–82.CrossRefPubMedGoogle Scholar
  4. 4.
    Schirmer E.S., Glover J.R., Singer M.A., Lindquist S. 1996. HSP100/Clp proteins: A common mechanism explains diverse functions. Trends Biochem. Sci. 21, 289–296.PubMedGoogle Scholar
  5. 5.
    Hattendorf D.A., Lindquist S.L. 2002. Analysis of the AAA sensor-2 motif in the C-terminal ATPase domain of Hsp104 with a site-specific fluorescent probe of nucleotide binding. Proc. Natl. Acad. Sci. USA. 99, 2732–2737.CrossRefPubMedGoogle Scholar
  6. 6.
    Chernoff Y.O., Lindquist S., Ono B., Inge-Vechtomov S.G., Liebman S.W. Role of the chaperone protein Hsp104 in propagation of the yeast prion-like factor [PSI +]. Science. 268, 880–884.Google Scholar
  7. 7.
    Paushkin S.V., Kushnirov V.V., Smirnov V.N., Ter-Avanesyan M.D. 1996. Propagation of the yeast prionlike [psi +] determinant is mediated by oligomerization of the SUP35-encoded polypeptide chain release factor. EMBO J. 15, 3127–3134.PubMedGoogle Scholar
  8. 8.
    Kushnirov V., Ter-Avanesyan M. 1998. Structure and replication of yeast prions. Cell. 94, 13–16.CrossRefPubMedGoogle Scholar
  9. 9.
    Derkatch I.L., Bradley M.E., Zhou P., Chernoff Y.O., Liebman S.W. 1997. Genetic and environmental factors affecting the de novo appearance of the [PSI +] prion in Saccharomyces cerevisiae. Genetics. 147, 507–519.PubMedGoogle Scholar
  10. 10.
    Moriyama H., Edskes H.K., Wickner R.B. 2000. [URE3] Prion propagation in Saccharomyces cerevisiae: Requirement for chaperone Hsp104 and curing by overexpressed chaperone Ydj1p. Mol. Cell. Biol. 20, 8916–8922.CrossRefPubMedGoogle Scholar
  11. 11.
    Chernoff Y.O. 2004. Amyloidogenic domains, prions and structural inheritance: Rudiments of early life or recent acquisition? Curr. Opin. Chem. Biol. 8, 665–671.CrossRefPubMedGoogle Scholar
  12. 12.
    Prusiner S.B. 2001. Shattuck lecture: Neurodegenerative diseases and prions. N. Engl. J. Med. 344, 1516–1526.CrossRefPubMedGoogle Scholar
  13. 13.
    McKinley M.P., Bolton D.C., Prusiner S.B. 1983. A protease-resistant protein is a structural component of the scrapie prion. Cell. 35, 57–62.CrossRefPubMedGoogle Scholar
  14. 14.
    Fischer M., Rülicke T., Raeber A., Sailer A., Moser M., Oesch B., Brandner S., Aguzzi A., Weissmann C. 1996. Prion protein (PrP) with amino-proximal deletions restoring susceptibility of PrP knockout mice to scrapie. EMBO J. 15, 1255–1264.PubMedGoogle Scholar
  15. 15.
    Schirmer E.C., Lindquist S. 1997. Interactions of the chaperone Hsp104 with yeast Sup35 and mammalian PrP. Proc. Natl. Acad. Sci. USA. 94, 13 932–13 937.CrossRefGoogle Scholar
  16. 16.
    DebBurman S., Raymond G., Caughey B., Lindquist S. 1997. Chaperone-supervised conversion of prion protein to its protease-resistant form. Proc. Natl. Acad. Sci. USA. 94, 13 938–13 943.CrossRefGoogle Scholar
  17. 17.
    Chernoff Y., Galkin A., Lewitin E., Chernova T., Newnam G., Belenkiy S. 2000. Evolutionary conservation of prion-forming abilities of the yeast Sup35 protein. Mol. Microbiol. 35, 865–877.CrossRefPubMedGoogle Scholar
  18. 18.
    Maniatis T., Fritsch E.E., Sambrook J. 1982. Molecular Cloning. A Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Lab. Press.Google Scholar
  19. 19.
    Zakharov I.A., Kozhin S.A., Kozhina T.N., Fedorova I.V. 1984. Sbornik metodov po genetike drozhzhei-sakharomitsetov (Methods in Saccharomyces Yeast Genetics). Leningrad: Nauka.Google Scholar
  20. 20.
    Sherman F., Fink G.R., Hinks J.B. 1986. Methods in Yeast Genetics. Cold Spring Harbor., NY: Cold Spring Harbor Lab. Press.Google Scholar
  21. 21.
    Liu J.J., Lindquist S. 1999. Oligopeptide-repeat expansions modulate “protein-only“ inheritance in yeast. Nature. 400, 573–576.CrossRefPubMedGoogle Scholar
  22. 22.
    Narwa R., Harris D.A. 1999. Prion proteins carrying pathogenic mutations are resistant to phospholipase cleavage of their glycolipid anchors. Biochemistry. 38, 8770–8777.CrossRefPubMedGoogle Scholar
  23. 23.
    Wegrzyn R.D., Bapat K., Newnam G.P., Zink A.D., Chernoff Y.O. 2001. Mechanism of prion loss after Hsp104 inactivation in yeast. Mol. Cell Biol. 21, 4656–4669.CrossRefPubMedGoogle Scholar
  24. 24.
    Parsell D.A., Sanchez Y., Stitzel J.D., Lindquist S. 1991. Hsp104 is a highly conserved protein with two essential nucleotide-binding sites. Nature. 353, 270–283.CrossRefPubMedGoogle Scholar
  25. 25.
    Bonneaud N., Ozier-Kalogeropoulos O., Li G.Y., Labouesse M., Minvielle-Sebastia L., Lacroute F. 1991. A family of low and high copy replicative, integrative and single-stranded S. cerevisiae/E. coli shuttle vectors. Yeast. 7, 609–615.CrossRefPubMedGoogle Scholar
  26. 26.
    Chernoff Y.O., Uptain S.M., Lindquist S.L. 2002. Analysis of prion factors in yeast. Methods Enzymol. 351, 499–538.CrossRefPubMedGoogle Scholar
  27. 27.
    Sachs A.B., Sarnow P., Hentze M.W. Starting at the beginning, middle, and end: Translation initiation in eukaryotes. Cell. 89, 831–838.Google Scholar
  28. 28.
    Zhou W., Edelman G.M., Mauro V.P. 2001. Transcript leader regions of two Saccharomyces cerevisiae mRNAs contain internal ribosome entry sites that function in living cells. Proc. Natl. Acad. Sci. USA. 98, 531–536.CrossRefGoogle Scholar
  29. 29.
    Santanu Raychaudhuri S., Fontanes V., Banerjee R., Bernavichute Y., Dasgupta A. Zuotin. 2006. A DnaJ molecular chaperone stimulates cap-independent translation in yeast. Biochem. Biophys. Res. Comm. 350, 788–795.CrossRefPubMedGoogle Scholar
  30. 30.
    Gallie D.R., Sleat D.E., Watts J.W., Turner P.C., Wilson M.A. 1987. The 5′-leader sequence of tobacco mosaic virus RNA enhances the expression of foreign gene transcripts in vitro and in vivo. Nucleic Acids Res. 15, 3257–3273.CrossRefPubMedGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2008

Authors and Affiliations

  • A. A. Rubel
    • 1
  • A. F. Saifitdinova
    • 1
  • A. G. Lada
    • 2
  • A. A. Nizhnikov
    • 2
  • S. G. Inge-Vechtomov
    • 1
    • 2
  • A. P. Galkin
    • 1
  1. 1.St. Petersburg Branch, Vavilov Institute of General GeneticsRussian Academy of SciencesSt. PetersburgRussia
  2. 2.St. Petersburg State UniversitySt. PetersburgRussia

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