Cellular factors important for the de novo formation of yeast prions.

Cellular factors important for the de novo formation of yeast prions.
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对于酵母朊病毒的从头形成很重要的细胞因子。

DOI:
10.1042/bst0361083
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发表时间:
2008
影响因子:
3.9
通讯作者:
Tuite M
Tuite M
中科院分区:
生物学3区
文献类型:
--
作者:
Tuite M

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朊病毒代表了一种不寻常的结构形式的蛋白质,是“传染性”。在哺乳动物中,朊病毒与致命的神经退行性疾病如克雅氏病(Creutzfeldt-Jakob disease)有关,而在真菌中,它们作为表型的新表观遗传调节因子。尽管大多数人类朊病毒疾病是自发产生的,但我们对传染性朊病毒如何从头形成仍然知之甚少。酵母菌的[PSI+]朊病毒提供了一个高度易处理的模型,在其中探索从头朊病毒形成的潜在机制,特别是识别关键的顺式和反式作用因子。最重要的是,[PSI+]的新生需要第二种称为[PIN+]的朊病毒的存在,它通常是Rnq 1 p的朊病毒形式,Rnq 1 p是一种富含谷氨酰胺和天冬氨酸残基的蛋白质。[PIN+]朊病毒促进[PSI+]从头形成的分子机制尚未完全确定,但最有可能涉及某种形式的交叉播种。已知许多其他细胞因子,特别是热休克蛋白70(Hsp 70)家族的分子伴侣,可以改变酵母中从头形成的频率。
Prions represent an unusual structural form of a protein that is ‘infectious’. In mammals, prions are associated with fatal neurodegenerative diseases such as CJD (Creutzfeldt–Jakob disease), while in fungi they act as novel epigenetic regulators of phenotype. Even though most of the human prion diseases arise spontaneously, we still know remarkably little about how infectious prions formde novo. The [PSI+] prion of the yeastSaccharomyces cerevisiaeprovides a highly tractable model in which to explore the underlying mechanism ofde novoprion formation, in particular identifying keycis- andtrans-acting factors. Most significantly, thede novoformation of [PSI+] requires the presence of a second prion called [PIN+], which is typically the prion form of Rnq1p, a protein rich in glutamine and aspartic acid residues. The molecular mechanism by which the [PIN+] prion facilitatesde novo[PSI+] formation is not fully established, but most probably involves some form of cross-seeding. A number of other cellular factors, in particular chaperones of the Hsp70 (heat-shock protein 70) family, are known to modify the frequency ofde novoprion formation in yeast.
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