Meddling with Fate: The Proteasomal Deubiquitinating Enzymes.
Meddling with Fate: The Proteasomal Deubiquitinating Enzymes.
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DOI：
10.1016/j.jmb.2017.09.015
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发表时间：
2017-11-10
影响因子：
5.6
通讯作者：
Finley D
中科院分区：
文献类型：
--
作者：
de Poot SAH;Tian G;Finley D
三种去泛素酶-Rpn11、Usp14和Uch37-与蛋白酶体调节颗粒有关。这些酶允许蛋白酶体在将泛素转移到核心颗粒进行降解之前从底物中去除泛素。尽管转位通道对于折叠的蛋白质来说太窄了，但转位的力量会机械地将它们展开。随着转运的进行，与底物结合的泛素链被吸引到通道的入口处，在那里它们可以阻碍进一步的转运。Rpn11位于端口上方，可以在不影响降解的情况下移除这些链，因为在Rpn11起作用之前，底物必须不可逆转地致力于降解。Rpn11的INS-1环确保了去泛素化和底物降解之间的耦合，该环控制泛素进入其催化部位。与Rpn11相反，Usp14和Uch37可以在承诺步骤之前促进底物从蛋白酶体解离，从而使底物免于降解。Uch37的独特之处在于它既是蛋白酶体的组成部分，也是第二个多亚基组装的组件，即INO80复合体。然而，只有重新进入蛋白酶体才能激活Uch37。招募到蛋白酶体同样激活了Usp14。然而，Usp14对蛋白酶体的影响取决于底物，因为它对携带多个泛素链的蛋白质有明显的偏好。USP14对蛋白酶体施加复杂的控制，即使在去泛素化不活跃的情况下也抑制蛋白酶体的活性。该领域的一个主要挑战将是更深入地阐明Rpn11、Usp14和Uch37的特异性，不仅使用体外模型底物，而且使用它们的内源性靶标。
Three deubiquitinating enzymes–Rpn11, Usp14, and Uch37–are associated with the proteasome regulatory particle. These enzymes allow proteasomes to remove ubiquitin from substrates before they are translocated into the core particle to be degraded. Although the translocation channel is too narrow for folded proteins, the force of translocation unfolds them mechanically. As translocation proceeds, ubiquitin chains bound to substrate are drawn to the channel’s entry port, where they can impede further translocation. Rpn11, situated over the port, can remove these chains without compromising degradation because substrates must be irreversibly committed to degradation before Rpn11 acts. This coupling between deubiquitination and substrate degradation is ensured by the Ins-1 loop of Rpn11, which controls ubiquitin access to its catalytic site. In contrast to Rpn11, Usp14 and Uch37 can rescue substrates from degradation by promoting substrate dissociation from the proteasome prior to the commitment step. Uch37 is unique in being a component of both the proteasome and a second multisubunit assembly, the INO80 complex. However, only recruitment into the proteasome activates Uch37. Recruitment to the proteasome likewise activates Usp14. However, the influence of Usp14 on the proteasome depends on the substrate, due to its marked preference for proteins that carry multiple ubiquitin chains. Usp14 exerts complex control over the proteasome, suppressing proteasome activity even when inactive in deubiquitination. A major challenge for the field will be to elucidate the specificities of Rpn11, Usp14, and Uch37 in greater depth, employing not only model in vitro substrates, but their endogenous targets.
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影响因子：
23.9
作者：
Buckley, Shannon M.;Aranda-Orgilles, Beatriz;Strikoudis, Alexandros;Apostolou, Effie;Loizou, Evangelia;Moran-Crusio, Kelly;Farnsworth, Charles L.;Koller, Antonius A.;Dasgupta, Ramanuj;Silva, Jeffrey C.;Stadtfeld, Matthias;Hochedlinger, Konrad;Chen, Emily I.;Aifantis, Iannis
通讯作者：
Aifantis, Iannis
DOI：
10.1523/jneurosci.2635-09.2009
发表时间：
2009-09-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Chen PC;Qin LN;Li XM;Walters BJ;Wilson JA;Mei L;Wilson SM
通讯作者：
Wilson SM
影响因子：
5.5
作者：
Bhattacharyya, Bula J.;Wilson, Scott M.;Miller, Richard J.
通讯作者：
Miller, Richard J.
DOI：
10.1073/pnas.1608644113
发表时间：
2016-08-09
影响因子：
11.1
作者：
Braten, Ori;Livneh, Ido;Ciechanover, Aaron
通讯作者：
Ciechanover, Aaron
影响因子：
16
作者：
Chen X;Walters KJ
通讯作者：
Walters KJ