Numerous proteins with unique characteristics are degraded by the 26S proteasome following monoubiquitination
Numerous proteins with unique characteristics are degraded by the 26S proteasome following monoubiquitination
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DOI：
10.1073/pnas.1608644113
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发表时间：
2016-08-09
影响因子：
11.1
通讯作者：
Ciechanover, Aaron
中科院分区：
文献类型：
--
作者：
Braten, Ori;Livneh, Ido;Ciechanover, Aaron
“经典的”蛋白酶体降解信号是一种底物锚定的多聚泛素链。然而，少数蛋白质已被证明在单泛素化之后被靶向。在这项研究中，我们在人类细胞和酵母细胞中建立了一种用于鉴定依赖单泛素化的蛋白酶体底物的系统性方法。细胞内野生型可聚合泛素被不能形成链的泛素所取代。通过蛋白质组学分析，我们筛选出在这些条件下仍然被降解的底物，与之相对的是那些被稳定的底物，因此后者需要多聚泛素化才能被降解。对于随机抽样的代表性底物，我们证实它们的细胞稳定性与我们的筛选预测相符。重要的是，这两组底物显示出独特的特征：单泛素化底物比多聚泛素化底物更小，在特定途径中富集，并且在人类中结构上更有序。我们认为依赖单泛素化的降解比之前所设想的更为普遍，并在各种细胞过程中发挥关键作用。
The "canonical" proteasomal degradation signal is a substrate-anchored polyubiquitin chain. However, a handful of proteins were shown to be targeted following monoubiquitination. In this study, we established-in both human and yeast cells-a systematic approach for the identification of monoubiquitination-dependent proteasomal substrates. The cellular wild-type polymerizable ubiquitin was replaced with ubiquitin that cannot form chains. Using proteomic analysis, we screened for substrates that are nevertheless degraded under these conditions compared with those that are stabilized, and therefore require polyubiquitination for their degradation. For randomly sampled representative substrates, we confirmed that their cellular stability is in agreement with our screening prediction. Importantly, the two groups display unique features: monoubiquitinated substrates are smaller than the polyubiquitinated ones, are enriched in specific pathways, and, in humans, are structurally less disordered. We suggest that monoubiquitination-dependent degradation is more widespread than assumed previously, and plays key roles in various cellular processes.