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Molecular and Cellular Biology, January 2009, p. 187-200, Vol. 29, No. 1
0270-7306/09/$08.00+0     doi:10.1128/MCB.02271-07
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Ssd1 Is Required for Thermotolerance and Hsp104-Mediated Protein Disaggregation in Saccharomyces cerevisiae{triangledown}

Snober S. Mir, David Fiedler, and Anil G. Cashikar*

Center for Molecular Chaperones, Radiobiology and Cancer Virology, Medical College of Georgia, Augusta, Georgia 30912

Received 21 December 2007/ Returned for modification 4 March 2008/ Accepted 9 October 2008

In the budding yeast Saccharomyces cerevisiae, the Hsp104-mediated disaggregation of protein aggregates is essential for thermotolerance and to facilitate the maintenance of prions. In humans, protein aggregation is associated with neuronal death and dysfunction in many neurodegenerative diseases. Mechanisms of aggregation surveillance that regulate protein disaggregation are likely to play a major role in cell survival after acute stress. However, such mechanisms have not been studied. In a screen using the yeast gene deletion library for mutants unable to survive an aggregation-inducing heat stress, we find that SSD1 is required for Hsp104-mediated protein disaggregation. SSD1 is a polymorphic gene that plays a role in cellular integrity, longevity, and pathogenicity in yeast. Allelic variants of SSD1 regulate the level of thermotolerance and cell wall remodeling. We have shown that Ssd1 influences the ability of Hsp104 to hexamerize, to interact with the cochaperone Sti1, and to bind protein aggregates. These results provide a paradigm for linking Ssd1-mediated cellular integrity and Hsp104-mediated disaggregation to ensure the survival of cells with fewer aggregates.


* Corresponding author. Mailing address: Medical College of Georgia, 1410 Laney Walker Blvd. CN3150, Augusta, GA 30912. Phone: (706) 721-6890. Fax: (706) 721-0101. E-mail: acashikar{at}mcg.edu

{triangledown} Published ahead of print on 20 October 2008.


Molecular and Cellular Biology, January 2009, p. 187-200, Vol. 29, No. 1
0270-7306/09/$08.00+0     doi:10.1128/MCB.02271-07
Copyright © 2009, American Society for Microbiology. All Rights Reserved.




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