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Protein disaggregation mediated by heat-shock protein Hspl04

Abstract

THE heat-inducible members of the HsplOO (or Clp) family of proteins share a common function in helping organisms to survive extreme stress, but the basic mechanism through which these pro-teins function is not understood1–5. Hspl04 protects cells against a variety of stresses, under many physiological conditions6,7, and its function has been evolutionarily conserved, at least from Saccharomyces cerevisiae to Arabidopsis thaliana25. Homology with the Escherichia coli Clp A protein suggests that Hspl04 may provide stress tolerance by helping to rid the cell of heat-denatured proteins through proteolysis1. But genetic analysis indicates that Hspl04 may function like Hsp70 as a molecular chaperone8. Here we investigate the role of Hspl04 in vivo using a temperature-sensitiveVibrio harveyi luciferase-fusion protein as a test substrate9. We find that Hspl04 does not protect luciferase from thermal denaturation, nor does it promote proteolysis of luciferase. Rather, Hspl04 functions in a manner not previously described for other heat-shock proteins: it mediates the resolubilization of heat-inactivated luciferase from insoluble aggregates.

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References

  1. Gottesman, S. et al. Proc. natn. Acad. Sci. U.S.A. 87, 3513–3517 (1990).

    Article  ADS  CAS  Google Scholar 

  2. Parsell, D. A., Sanchez, Y., Stitzel, J. D. & Lindquist, S. Nature 353, 270–273 (1991).

    Article  ADS  CAS  Google Scholar 

  3. Squires, C. L., Pedersen, S., Ross, B. M. & Squires, C. J. Bact. 173, 4254–4262 (1991).

    Article  CAS  Google Scholar 

  4. Squires, C. & Squires, C. L. J. Bact. 174, 1081–1085 (1992).

    Article  CAS  Google Scholar 

  5. Kruger, E., Volker, U. & Hecker, M. J. Bact. 176, 3360–3367 (1994).

    Article  CAS  Google Scholar 

  6. Sanchez, Y., Taulien, J., Borkovich, K. A., & Lindquist, S. EMBO J. 11, 2357–2364 (1992).

    Article  CAS  Google Scholar 

  7. Sanchez, Y. & Lindquist, S. L. Science 248, 1112–1115 (1990).

    Article  ADS  CAS  Google Scholar 

  8. Sanchez, Y. et al. J. Bact. 175, 6484–6491 (1993).

    Article  CAS  Google Scholar 

  9. Escher, A., O'Kane, D. J., Lee, J. & Szalay, A. A. Proc. natn. Acad. Sci. U.S.A. 86, 6528–6532 (1989).

    Article  ADS  CAS  Google Scholar 

  10. Schroder, H. T., Langer, T., Hartl, F.-U. & Bukau, B. EMBO J. 12, 4137–4144 (1993).

    Article  CAS  Google Scholar 

  11. Webster, D. L. & Watson, K. Yeast 9, 1165–1175 (1993).

    Article  CAS  Google Scholar 

  12. Skowyra, D., Georgopoulos, C. & Zylicz, M. Cell 62, 939–944 (1990).

    Article  CAS  Google Scholar 

  13. Shanen, S. L. et al. Biochemistry 21, 5539–5551 (1982).

    Article  Google Scholar 

  14. Wickner, S., Hoskins, J. & McKenney, K. Nature 350, 165–167 (1991).

    Article  ADS  CAS  Google Scholar 

  15. Wickner, S., Hoskins, J. & McKenney, K. Proc. natn. Acad. Sci. U.S.A. 88, 7903–7907 (1991).

    Article  ADS  CAS  Google Scholar 

  16. Langer, T. et al. Nature 356, 683–689 (1992).

    Article  ADS  CAS  Google Scholar 

  17. Parsell, D. A. & Lindquist, S. A. Rev. Genet. 27, 437–496 (1993).

    Article  CAS  Google Scholar 

  18. Feder, J. J., Rossi, J. M., Solomon, J., Solomon, N. & Lindquist, S. Genes Dev. 6, 1402–1413 (1992).

    Article  CAS  Google Scholar 

  19. Treco, D. A. in Current Protocols in Molecular Biology (eds Ausubel, F. M., Brent, R. & Kingston, R. E.) 13.1.1–13.1.7 (Wiley, New York, 1989).

    Google Scholar 

  20. Kurtz, S., Gordon, E. & Lindquist, S. L. in Sequence Specificity in Transcription and Translation 611–620 (Liss, New York, 1985).

    Google Scholar 

  21. Laemmli, U. K. Nature 227, 680–685 (1970).

    Article  ADS  CAS  Google Scholar 

  22. Wright, R. & Rine, J. in Methods in Cell Biology (ed. Tartakoff, A. M.) 473–512 (Academic, New York. 1989).

    Google Scholar 

  23. Byers, B. & Goetsch, L. Meth. Enzym. 194, 602–608 (1991).

    Article  CAS  Google Scholar 

  24. van Tuinen, E. & Riezman, H. J. Histochem. Cytochem. 35, 327–333 (1987).

    Article  CAS  Google Scholar 

  25. Schirmer, E., Lindquist, S. & Vierling, E. Pl. Cell (in the press).

Download references

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Parsell, D., Kowal, A., Singer, M. et al. Protein disaggregation mediated by heat-shock protein Hspl04. Nature 372, 475–478 (1994). https://doi.org/10.1038/372475a0

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