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首页> 外文期刊>Molecular and Cellular Biology >Proteasome-Mediated Degradation of Cotranslationally Damaged Proteins Involves Translation Elongation Factor 1A
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Proteasome-Mediated Degradation of Cotranslationally Damaged Proteins Involves Translation Elongation Factor 1A

机译：蛋白酶体介导的共翻译受损蛋白降解涉及翻译延伸因子1A。

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Rad23 and Rpn10 play synergistic roles in the recognition of ubiquitinated proteins by the proteasome, and loss of both proteins causes growth and proteolytic defects. However, the physiological targets of Rad23 and Rpn10 have not been well defined. We report that rad23Δ rpn10Δ is unable to grow in the presence of translation inhibitors, and this sensitivity was suppressed by translation elongation factor 1A (eEF1A). This discovery suggested that Rad23 and Rpn10 perform a role in translation quality control. Certain inhibitors increase translation errors during protein synthesis and cause the release of truncated polypeptide chains. This effect can also be mimicked by ATP depletion. We determined that eEF1A interacted with ubiquitinated proteins and the proteasome following ATP depletion. eEF1A interacted with the proteasome subunit Rpt1, and the turnover of nascent damaged proteins was deficient in rpt1. An eEF1A mutant (eEF1AD156N) that conferred hyperresistance to translation inhibitors was much more effective at eliminating damaged proteins and was detected in proteasomes in untreated cells. We propose that eEF1A is well suited to detect and promote degradation of damaged proteins because of its central role in translation elongation. Our findings provide a mechanistic foundation for defining how cellular proteins are degraded cotranslationally.
机译：Rad23和Rpn10在蛋白酶体识别泛素化蛋白中发挥协同作用，两种蛋白的缺失都会导致生长和蛋白水解缺陷。但是，Rad23和Rpn10的生理指标尚未明确。我们报道 rad23 Δ rpn10 Δ在翻译抑制剂存在下无法生长，并且这种敏感性被翻译延伸因子1A（eEF1A）抑制。该发现表明Rad23和Rpn10在翻译质量控制中起作用。某些抑制剂会增加蛋白质合成过程中的翻译错误，并导致截短的多肽链释放。 ATP耗竭也可以模仿这种效果。我们确定eEF1A与ATP耗尽后与泛素化蛋白和蛋白酶体相互作用。 eEF1A与蛋白酶体亚基Rpt1相互作用，新生的受损蛋白质的周转率不足 rpt1 。赋予翻译抑制剂高抗性的eEF1A突变体（eEF1A D156N ）在消除损坏的蛋白质上更为有效，并且在未经处理的细胞中的蛋白酶体中被检测到。我们建议eEF1A非常适合检测和促进受损蛋白的降解，因为它在翻译延伸中起着核心作用。我们的发现为定义细胞蛋白如何共翻译降解提供了机制基础。

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