Principles of cotranslational ubiquitination and quality control at the ribosome.

Principles of cotranslational ubiquitination and quality control at the ribosome.
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DOI:
10.1016/j.molcel.2013.03.010
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发表时间:
2013-05-09
期刊:
影响因子:
16
通讯作者:
Frydman, Judith
Frydman, Judith
中科院分区:
生物学1区
文献类型:
--
作者:
Duttler, Stefanie;Pechmann, Sebastian;Frydman, Judith

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Achieving efficient cotranslational folding of their complex proteomes poses a challenge for eukaryotic cells. Nascent polypeptides emerging vectorially from the ribosome often cannot fold stably and may be susceptible to misfolding and degradation. The extent to which nascent chains are subject to cotranslational quality control and degradation remains unclear. Here, we directly and quantitatively assess cotranslational ubiquitination and identify, at a systems level, the determinants and factors governing this process. Cotranslational ubiquitination occurs at very low levels, and is carried out by a complex network of E3 ubiquitin ligases. Ribosome-associated chaperones and cotranslational folding protect the majority of nascent chains from premature quality control. Nonetheless, a number of nascent chains whose intrinsic properties hinder efficient cotranslational folding remain susceptible for cotranslational ubiquitination. We find that quality control at the ribosome is achieved through a tiered system, where nascent polypeptides first have a chance to fold before becoming accessible to ubiquitination.
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