This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Melville, M. W.
Right arrow Articles by Frydman, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Melville, M. W.
Right arrow Articles by Frydman, J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2003, p. 3141-3151, Vol. 23, No. 9
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.9.3141-3151.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The Hsp70 and TRiC/CCT Chaperone Systems Cooperate In Vivo To Assemble the Von Hippel-Lindau Tumor Suppressor Complex

Mark W. Melville,1,{dagger} Amie J. McClellan,1 Anne S. Meyer,1 Andre Darveau,2 and Judith Frydman1*

Department of Biological Sciences, Stanford University, Stanford, California 94305,1 Departement de Biochimie et Microbiologie, CREFSIP, Université Laval, Sainte-Foy, Quebec, Canada2

Received 16 September 2002/ Returned for modification 4 November 2002/ Accepted 10 February 2003

The degree of cooperation and redundancy between different chaperones is an important problem in understanding how proteins fold in the cell. Here we use the yeast Saccharomyces cerevisiae as a model system to examine in vivo the chaperone requirements for assembly of the von Hippel-Lindau protein (VHL)-elongin BC (VBC) tumor suppressor complex. VHL and elongin BC expressed in yeast assembled into a correctly folded VBC complex that resembles the complex from mammalian cells. Unassembled VHL did not fold and remained associated with the cytosolic chaperones Hsp70 and TRiC/CCT, in agreement with results from mammalian cells. Analysis of the folding reaction in yeast strains carrying conditional chaperone mutants indicates that incorporation of VHL into VBC requires both functional TRiC and Hsp70. VBC assembly was defective in cells carrying either a temperature-sensitive ssa1 gene as their sole source of cytosolic Hsp70/SSA function or a temperature-sensitive mutation in CCT4, a subunit of the TRiC/CCT complex. Analysis of the VHL-chaperone interactions in these strains revealed that the cct4ts mutation decreased binding to TRiC but did not affect the interaction with Hsp70. In contrast, loss of Hsp70 function disrupted the interaction of VHL with both Hsp70 and TRiC. We conclude that, in vivo, folding of some polypeptides requires the cooperation of Hsp70 and TRiC and that Hsp70 acts to promote substrate binding to TRiC.

* Corresponding author. Mailing address: Department of Biological Sciences, Stanford University, Stanford, CA 94305. Phone: (650) 725-7833. Fax: (650) 723-8475. E-mail: jfrydman{at}stanford.edu.

{dagger} Present address: Wyeth BioPharma, Andover, MA 01810.

Molecular and Cellular Biology, May 2003, p. 3141-3151, Vol. 23, No. 9
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.9.3141-3151.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Abe, Y., Yoon, S.-O., Kubota, K., Mendoza, M. C., Gygi, S. P., Blenis, J. (2009). p90 Ribosomal S6 Kinase and p70 Ribosomal S6 Kinase Link Phosphorylation of the Eukaryotic Chaperonin Containing TCP-1 to Growth Factor, Insulin, and Nutrient Signaling. J. Biol. Chem. 284: 14939-14948 [Abstract] [Full Text]  
  • Piessevaux, J., De Ceuninck, L., Catteeuw, D., Peelman, F., Tavernier, J. (2008). Elongin B/C Recruitment Regulates Substrate Binding by CIS. J. Biol. Chem. 283: 21334-21346 [Abstract] [Full Text]  
  • Yam, A. Y.-W., Albanese, V., Lin, H.-T. J., Frydman, J. (2005). Hsp110 Cooperates with Different Cytosolic HSP70 Systems in a Pathway for de Novo Folding. J. Biol. Chem. 280: 41252-41261 [Abstract] [Full Text]  
  • Bansal, P. K., Abdulle, R., Kitagawa, K. (2004). Sgt1 Associates with Hsp90: an Initial Step of Assembly of the Core Kinetochore Complex. Mol. Cell. Biol. 24: 8069-8079 [Abstract] [Full Text]  
  • Sutovsky, H., Gazit, E. (2004). The von Hippel-Lindau Tumor Suppressor Protein Is a Molten Globule under Native Conditions: IMPLICATIONS FOR ITS PHYSIOLOGICAL ACTIVITIES. J. Biol. Chem. 279: 17190-17196 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»