Abstract
The yeast prion [PSI +] is a self-perpetuating aggregated isoform of the translation termination factor Sup35. [PSI +] propagation is promoted by moderate levels and antagonized by high levels of the chaperone Hsp104. In agreement with the model postulating that excess Hsp104 acts on [PSI +] by disaggregating prion polymers, we show that an increase in Sup35 levels, accompanied by an increase in size of prion aggregates, also partially protects [PSI +] from elimination by excess Hsp104. Despite retention of [PSI +], excess Hsp104 decreases toxicity of overproduced Sup35 in [PSI +] strains. A heritable variant of [PSI +], which has been isolated and is maintained only in the presence of increased levels of Hsp104, is characterized by an abnormally large aggregate size, and exhibits an altered response to overproduction of the Hsp70 chaperone Ssa1. These features resemble the previously described prion generated by a deletion derivative of Sup35, but are not associated with any sequence alteration and are controlled exclusively at the protein level. Our data provide a proof of the existence of conditionally stable prion variants maintained only at altered levels of Hsps, that could in principle be beneficial if the normal cellular function of a prion protein becomes detrimental to the cell in such conditions.
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Acknowledgements
We thank K. Gokhale and E. Lewitin for help in the strain and plasmid constructions, and D. Bedwell, S. Lindquist, and J. Weissman for plasmids and antibodies. This work was supported by grants RB1-2336-ST02 to S. G. I.-V. and Y. O. C.; and ST-012-02 (YI-B-12-06) to A. S. B. from US Civilian Research and Development Foundation; R01GM58763 to Y. O. C. from National Institutes of Health; and 03-04-49335 to A. S. B. from Russian Foundation for Basic Research.
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Communicated by S. Liebman
A. S. Borchsenius and S. Müller contributed equally to this study.
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Borchsenius, A.S., Müller, S., Newnam, G.P. et al. Prion variant maintained only at high levels of the Hsp104 disaggregase. Curr Genet 49, 21–29 (2006). https://doi.org/10.1007/s00294-005-0035-0
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DOI: https://doi.org/10.1007/s00294-005-0035-0