The Not4 RING E3 Ligase: A Relevant Player in Cotranslational Quality Control.
The Not4 RING E3 Ligase: A Relevant Player in Cotranslational Quality Control.
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DOI：
10.1155/2013/548359
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发表时间：
2013-01-01
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影响因子：
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通讯作者：
Collart, Martine A
中科院分区：
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作者：
Collart, Martine A
Not4环E3连接酶是进化上保守的CCR4-Not复合体的一个亚基。最初在酵母中通过增加转录的突变来鉴定，后来被定义为泛素连接酶。这种连接酶的底物在酵母和后生动物中得到了表征。有趣的是，这种连接酶的一些底物是针对多泛素化和降解的，而另一些则是稳定的单泛素化蛋白。前者主要参与转录，而后者是一种核糖体蛋白和核糖体相关的伴侣。一致地，Not4和CCR4-Not复合体的所有其他亚基都存在于翻译核糖体中。Not4在协译质量控制中的重要作用已经显现。在没有Not4的情况下，多聚体的总水平降低。此外，翻译上滞留的多肽、聚集蛋白和多泛素化蛋白也会积累。它在质量控制中的作用可能一方面与它对蛋白酶体功能组装的重要性有关，另一方面与它与RNA降解机器的联系有关。Not4处于向翻译被中止的降解mRNAs发送信号的理想位置，这将Not4定义为新合成蛋白质的质量控制中的关键角色。
The Not4 RING E3 ligase is a subunit of the evolutionarily conserved Ccr4-Not complex. Originally identified in yeast by mutations that increase transcription, it was subsequently defined as an ubiquitin ligase. Substrates for this ligase were characterized in yeast and in metazoans. Interestingly, some substrates for this ligase are targeted for polyubiquitination and degradation, while others instead are stable monoubiquitinated proteins. The former are mostly involved in transcription, while the latter are a ribosomal protein and a ribosome-associated chaperone. Consistently, Not4 and all other subunits of the Ccr4-Not complex are present in translating ribosomes. An important function for Not4 in cotranslational quality control has emerged. In the absence of Not4, the total level of polysomes is reduced. In addition, translationally arrested polypeptides, aggregated proteins, and polyubiquitinated proteins accumulate. Its role in quality control is likely to be related on one hand to its importance for the functional assembly of the proteasome and on the other hand to its association with the RNA degradation machines. Not4 is in an ideal position to signal to degradation mRNAs whose translation has been aborted, and this defines Not4 as a key player in the quality control of newly synthesized proteins.