A Cotranslational Ubiquitination Pathway for Quality Control of Misfolded Proteins

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• 作者：Feng Wang¹ ; Larissa A. Durfee¹ ; Jon M. Huibregtse¹ ; ^{huibregtse@austin.utexas.edu}
• 刊名：Molecular Cell
• 出版年：2013
• 出版时间：9 May, 2013
• 年：2013
• 卷：50
• 期：3
• 页码：368-378
• 全文大小：1517 K

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Summary

Previous studies have indicated that 6 % -30 % of 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 cotranslational 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 (CTU^S), the majority of nascent chain ubiquitination occurred within active translation complexes (CTU^A). CTU^A was increased in response to agents that induce protein misfolding, while CTU^S 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 CTU^A as a component of a quality control system that marks proteins for destruction while they are being synthesized.