Posttranscriptional Regulation of Glycoprotein Quality Control in the Endoplasmic Reticulum Is Controlled by the E2 Ub-Conjugating Enzyme UBC6e.
Posttranscriptional Regulation of Glycoprotein Quality Control in the Endoplasmic Reticulum Is Controlled by the E2 Ub-Conjugating Enzyme UBC6e.
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DOI：
10.1016/j.molcel.2016.07.014
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发表时间：
2016-09-01
期刊：
影响因子：
16
通讯作者：
Ploegh, Hidde L.
中科院分区：
文献类型：
--
作者：
Hagiwara, Masatoshi;Ling, Jingjing;Koenig, Paul-Albert;Ploegh, Hidde L.
内质网相关降解（ERAD）对内质网蛋白质量控制至关重要，不仅在内质网应激时如此，在内质网稳态时也是如此。我们报道了一个新的稳态控制层，其中ERAD活性本身是通过调节内源性EDEM1、OS-9和SEL1L （ERAD增强子）的水平而在转录后独立于未折叠蛋白反应进行调节的。功能性UBC6e需要其在内质网中的精确位置才能与Derlin2形成超分子复合物。这种复合物以ERAD增强子为目标进行降解，这一功能取决于UBC6e的酶活性。消融UBC6e导致活性ERAD增强子上调，从而不仅增加了末端错误折叠底物的清除率，还增加了在体外和体内折叠相对缓慢的野生型糖蛋白的清除率。因此，组成ERAD机制的蛋白质水平被仔细地调整和调整以适应普遍的需要。
Endoplasmic reticulum-associated degradation (ERAD) is essential for protein quality control in the ER, not only when the ER is stressed, but also at steady state. We report a new layer of homeostatic control, in which ERAD activity itself is regulated post-transcriptionally and independently of the unfolded protein response by adjusting the endogenous levels of EDEM1, OS-9 and SEL1L (ERAD enhancers). Functional UBC6e requires its precise location in the ER to form a supramolecular complex with Derlin2. This complex targets ERAD enhancers for degradation, a function that depends on UBC6e's enzymatic activity. Ablation of UBC6e causes up-regulation of active ERAD enhancers and so increases clearance not only of terminally misfolded substrates, but also of wild-type glycoproteins that fold comparatively slowly in vitro and in vivo. The levels of proteins that comprise the ERAD machinery are thus carefully tuned and adjusted to prevailing needs.
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影响因子：
16
作者：
Cormier, James H.;Tamura, Taku;Sunryd, Johan C.;Hebert, Daniel N.
通讯作者：
Hebert, Daniel N.
影响因子：
33.6
作者：
Guerriero CJ;Brodsky JL
通讯作者：
Brodsky JL
DOI：
10.1073/pnas.0805371105
发表时间：
2008-08-26
影响因子：
11.1
作者：
Mueller, Britta;Klemm, Elizabeth J.;Ploegh, Hidde L.
通讯作者：
Ploegh, Hidde L.
影响因子：
64.8
作者：
Lilley, BN;Ploegh, HL
通讯作者：
Ploegh, HL
影响因子：
4.8
作者：
Hirao, K;Natsuka, Y;Hosokawa, N
通讯作者：
Hosokawa, N