A cotranslational ubiquitination pathway for quality control of misfolded proteins.
A cotranslational ubiquitination pathway for quality control of misfolded proteins.
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DOI：
10.1016/j.molcel.2013.03.009
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发表时间：
2013-05-09
期刊：
影响因子：
16
通讯作者：
Huibregtse, Jon M.
中科院分区：
文献类型：
--
作者：
Wang, Feng;Durfee, Larissa A.;Huibregtse, Jon M.
先前的研究表明，所有新合成的蛋白质中有6-30%被泛素-蛋白酶体系统快速降解，但这些蛋白质的泛素化与翻译的关系尚不清楚。我们报告说，共翻译泛素化（CTU）是一个强大的过程中，约12-15%的新生多肽在人类细胞中被泛素化。CTU产物主要含有K48连接的多聚泛素链，与蛋白酶体靶向功能一致。虽然新生链先前已被证明在停滞复合物（CTUS）内泛素化，但大多数新生链泛素化发生在主动翻译复合物（CTUA）内。CTUA在诱导蛋白质错误折叠的试剂反应中增加，而CTUS在导致翻译错误或停滞的试剂反应中增加。这些结果表明，新生多肽的泛素化发生在两种情况下，并定义CTUA作为一个质量控制系统的组成部分，标记蛋白质的破坏，而它们正在合成。
Previous studies have indicated that 6–30% of all newly synthesized proteins are rapidly degraded by the ubiquitin-proteasome system, however the relationship of ubiquitination to translation for these proteins has been unclear. We report that co-translational ubiquitination (CTU) is a robust process, with ~12–15% of nascent polypeptides being ubiquitinated in human cells. CTU products contained primarily K48-linked polyubiquitin chains, consistent with a proteasomal targeting function. While nascent chains have been shown previously to be ubiquitinated within stalled complexes (CTUS), the majority of nascent chain ubiquitination occurred within active translation complexes (CTUA). CTUA was increased in response to agents that induce protein misfolding, while CTUS was increased in response to agents that lead to translational errors or stalling. These results indicate that ubiquitination of nascent polypeptides occurs in two contexts, and define CTUA as a component of a quality control system that marks proteins for destruction while they are being synthesized.
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DOI：
10.1042/bj20111220
发表时间：
2012-03-15
期刊：
The Biochemical journal
影响因子：
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作者：
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通讯作者：
Pritchard JK
DOI：
10.1007/978-1-61779-005-8_19
发表时间：
2011
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
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作者：
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Nicchitta, Christopher V
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作者：
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影响因子：
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作者：
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通讯作者：
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