Kirkland PA, Reidy M, Masison DC

Replication of amyloid-based yeast prions [PSI(+)], [URE3] and [PIN(+)] depends on the protein disaggregation machinery that includes Hsp104, Hsp70 and Hsp40 molecular chaperones. Yet, overexpressing Hsp104 cures cells of [PSI(+)] prions. An Hsp70 mutant (Ssa1-21p) antagonizes propagation of [PSI(+)] in a manner resembling elevated Hsp104. The major cytosolic Hsp40 Sis1p ...

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is the only Hsp40 required for replication of these prions, but it's role in [PSI(+)] curing is unknown. Here we find that all non-essential functional regions of Sis1p are dispensable for [PSI(+)] propagation, suggesting that other Hsp40s might provide Hsp40 functions required for [PSI(+)] replication. Conversely, several Sis1p functions were important for promoting anti-prion effects of both Ssa1-21p and Hsp104, which implies a link between the anti-prion effects of these chaperones and suggests that Sis1p is a specific Hsp40 important for [PSI(+)] curing. These contrasting findings suggest that the functions of Hsp104 that are important for propagation and elimination of [PSI(+)] are either distinct or specified by different Hsp40s. This work also uncovered a growth inhibition caused by [PSI(+)] when certain functions of Sis1p were absent, suggesting that Sis1p protects cells from cytotoxicity caused by [PSI(+)] prions.

Date: May. 09, 2011

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