Prion induction by the short-lived, stress-induced protein Lsb2 is regulated by ubiquitination and association with the actin cytoskeleton.
Prion induction by the short-lived, stress-induced protein Lsb2 is regulated by ubiquitination and association with the actin cytoskeleton.
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DOI：
10.1016/j.molcel.2011.07.001
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发表时间：
2011-07-22
期刊：
影响因子：
16
通讯作者：
Wilkinson KD
中科院分区：
文献类型：
--
作者：
Chernova TA;Romanyuk AV;Karpova TS;Shanks JR;Ali M;Moffatt N;Howie RL;O'Dell A;McNally JG;Liebman SW;Chernoff YO;Wilkinson KD
酵母朊病毒是自我永存的富含QN的淀粉样蛋白，其控制可遗传的性状并作为哺乳动物淀粉样变性的模型。由过度产生的朊病毒蛋白重新形成朊病毒是由其他聚集的富含QN的蛋白促进的，并且受到蛋白质稳态改变的影响。在这里，我们探索的机制，Las 17结合蛋白Lsb 2（Pin 3）促进翻译终止因子Sup 35转化为朊病毒形式[PSI+]。我们发现，Lsb 2本地化与一些Sup 35聚集体和Lsb 2是一个短暂的蛋白质，其水平通过泛素-蛋白酶体系统控制，并显着增加压力。Lsb 2的损失降低了短暂热休克后[PSI+]的稳定性。干扰Lsb 2泛素化的突变增加朊病毒诱导，而消除Lsb 2与肌动蛋白细胞骨架的关联的突变阻断其聚集和朊病毒诱导能力。这些发现直接牵连UPS和肌动蛋白细胞骨架调节朊病毒通过应激诱导的QN丰富的蛋白质。
Yeast prions are self-perpetuating QN-rich amyloids, that control heritable traits and serve as a model for mammalian amyloidoses. De novo prion formation by overproduced prion protein is facilitated by other aggregated QN-rich protein(s), and is influenced by alterations of protein homeostasis. Here we explore the mechanism by which the Las17-binding protein Lsb2 (Pin3) promotes conversion of the translation termination factor Sup35 into its prion form [PSI+]. We show that Lsb2 localizes with some Sup35 aggregates and that Lsb2 is a short-lived protein whose levels are controlled via the ubiquitin-proteasome system and are dramatically increased by stress. Loss of Lsb2 decreases stability of [PSI+] after brief heat shock. Mutations interfering with Lsb2 ubiquitination increase prion induction, while a mutation eliminating association of Lsb2 with the actin cytoskeleton blocks its aggregation and prion–inducing ability. These findings directly implicate the UPS and actin cytoskeleton in regulating prions via a stress-inducible QN-rich protein.
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影响因子：
21.3
作者：
Patel, Basant K.;Gavin-Smyth, Jackie;Liebman, Susan W.
通讯作者：
Liebman, Susan W.
新发现的朊病毒与酿酒酵母中染色质重塑因子 Swi1 相关
影响因子：
30.8
作者：
Du, Zhiqiang;Park, Kyung-Won;Li, Liming
通讯作者：
Li, Liming
DOI：
10.1073/pnas.0504882102
发表时间：
2005-07-26
影响因子：
11.1
作者：
Nakayashiki, T;Kurtzman, CP;Wickner, RB
通讯作者：
Wickner, RB
影响因子：
4.8
作者：
Allen, Kim D.;Chernova, Tatiana A.;Chernoff, Yury O.
通讯作者：
Chernoff, Yury O.
影响因子：
4.8
作者：
Kushnirov, Vitaly V.;Alexandrov, Ilya M.;Ter-Avanesyan, Michael D.
通讯作者：
Ter-Avanesyan, Michael D.