OVEREXPRESSION OF THE SUP45 GENE ENCODING A SUP35P-BINDING PROTEIN INHIBITS THE INDUCTION OF THE DE-NOVO APPEARANCE OF THE [PSI+] PRION

[PSI+], a non-Mendelian element found in some strains of Saccharomyces cerevisiae, is presumed to be the manifestation of a self-propagating prion conformation of eRF3 (Sup35p). Translation termination factor e RF3 enhances the activity of release factor eRF1 (Sup45p). As predicte d by the prion model, overproduction of Sup35p induces the de novo app earance of [PSI+]. However, another non-Mendelian determinant, [PIN+], is required for this induction. We now show that SUP45 overexpression inhibits the induction of [PSI+] by Sup35p overproduction in [PIN+] s trains, but has no effect on the propagation of [PSI+] or on the [PIN] status of the cells. We also show that SUP45 overexpression counterac ts the growth inhibition usually associated with overexpression of SUP 35 in [PSI+] strains. We argue that excess Sup45p inhibits [PSI+] seed formation. Because Sup35p complexes with Sup35p, we hypothesize that excess Sup45p may sequester Sup35p, thereby reducing the opportunity f or Sup35p conformational flips and/or self-interactions leading to pri on formation. This in vivo yeast result is reminiscent of the in vitro finding by investigators of Alzheimer disease that apolipoprotein E i nhibits amyloid nucleation, but does not reduce seeded growth of amylo id.