figure7

来自美国加州大学细胞与分子药理学系的Jonathan S. Weissman实验室发现核糖体质量控制复合物诱发新生肽降解并向翻译压力发出信号,这篇文章刊登在最新一期《CELL》杂志上。

-2012年11月21日《细胞》


中文翻译


【题目】核糖体质量控制复合物诱发新生肽降解并向翻译压力发出信号

【译文】保守的转录调节子热激因子1(Hsf1)是真核胞质溶胶中蛋白质毒性和其他压力的重要感受器。我们研究了酿酒酵母和78,000个双突变菌株中全基因组功能缺失库中Hsf1的活性,发现Hsf1活性在多种压力下被调控。这其中包括破坏的结合核蛋白体的复合物,我们把这种复合物称为核蛋白体质粒控制复合物(RQC),它包含了Ltn1 E3泛素连接酶、两个高度保守但研究很少的蛋白Tae2及Rqc1和Cdc48及其辅助因子。电子显微镜和生化分析显示RQC与含有多肽的60S核糖体亚基形成稳定的复合物,同时RQC可以催化它们的降解。一个负反馈回路调节RQC,并且Hsf1可以从其他压力中感知RQC介导的翻译压力信号。我们的工作揭示了Hsf1监测因子的压力范围并且解释了保守翻译的蛋白质质粒的控制机制。

英文原稿


[Title]A Ribosome-Bound Quality Control Complex Triggers Degradation of Nascent Peptides and Signals Translation Stress

[author]Onn Brandman, Jacob Stewart-Ornstein, Daisy Wong, Adam Larson, Christopher C. Williams, Gene-Wei Li, Sharleen Zhou, David King, Peter S. Shen, Jimena Weibezahn, Joshua G. Dunn, Silvi Rouskin, Toshifumi Inada, Adam Frost, Jonathan S. Weissman

[Abstract]The conserved transcriptional regulator heat shock factor 1 (Hsf1) is a key sensor of proteotoxic and other stress in the eukaryotic cytosol. We surveyed Hsf1 activity in a genome-wide loss-of-function library in Saccaromyces cerevisiae as well as ∼78,000 double mutants and found Hsf1 activity to be modulated by highly diverse stresses. These included disruption of a ribosome-bound complex we named the Ribosome Quality Control Complex (RQC) comprising the Ltn1 E3 ubiquitin ligase, two highly conserved but poorly characterized proteins (Tae2 and Rqc1), and Cdc48 and its cofactors. Electron microscopy and biochemical analyses revealed that the RQC forms a stable complex with 60S ribosomal subunits containing stalled polypeptides and triggers their degradation. A negative feedback loop regulates the RQC, and Hsf1 senses an RQC-mediated translation-stress signal distinctly from other stresses. Our work reveals the range of stresses Hsf1 monitors and elucidates a conserved cotranslational protein quality control mechanism.

原文地址

http://www.cell.com/abstract/S0092-8674(12)01339-6

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