Derkatch I L, Bradley M E, Liebman S W
Laboratory for Molecular Biology, Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2400-5. doi: 10.1073/pnas.95.5.2400.
[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 eRF3 enhances the activity of release factor eRF1 (Sup45p). As predicted by the prion model, overproduction of Sup35p induces the de novo appearance 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+] strains, but has no effect on the propagation of [PSI+] or on the [PIN] status of the cells. We also show that SUP45 overexpression counteracts the growth inhibition usually associated with overexpression of SUP35 in [PSI+] strains. We argue that excess Sup45p inhibits [PSI+] seed formation. Because Sup45p complexes with Sup35p, we hypothesize that excess Sup45p may sequester Sup35p, thereby reducing the opportunity for Sup35p conformational flips and/or self-interactions leading to prion formation. This in vivo yeast result is reminiscent of the in vitro finding by investigators of Alzheimer disease that apolipoprotein E inhibits amyloid nucleation, but does not reduce seeded growth of amyloid.
[PSI+]是在某些酿酒酵母菌株中发现的一种非孟德尔遗传元件，据推测是eRF3（Sup35p）自我传播的朊病毒构象的表现形式。翻译终止因子eRF3增强释放因子eRF1（Sup45p）的活性。正如朊病毒模型所预测的，Sup35p的过量表达会诱导[PSI+]的从头出现。然而，这种诱导需要另一种非孟德尔决定因素[PIN+]。我们现在表明，在[PIN+]菌株中，SUP45的过表达会抑制Sup35p过量表达对[PSI+]的诱导，但对[PSI+]的传播或细胞的[PIN]状态没有影响。我们还表明，SUP45的过表达会抵消通常与[PSI+]菌株中SUP35过表达相关的生长抑制。我们认为过量的Sup45p会抑制[PSI+]种子的形成。由于Sup45p与Sup35p形成复合物，我们推测过量的Sup45p可能会隔离Sup35p，从而减少Sup35p构象翻转和/或导致朊病毒形成的自相互作用的机会。酵母中的这一体内结果让人想起阿尔茨海默病研究人员在体外的发现，即载脂蛋白E抑制淀粉样蛋白成核，但不减少淀粉样蛋白的种子生长。
