Methionine Restriction Impairs Degradation of a Protein that Aberrantly Engages the Endoplasmic Reticulum Translocon.

Methionine Restriction Impairs Degradation of a Protein that Aberrantly Engages the Endoplasmic Reticulum Translocon.
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DOI:
10.17912/micropub.biology.001021
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发表时间:
2023
影响因子:
--
通讯作者:
Rubenstein, Eric M
Rubenstein, Eric M
中科院分区:
其他
文献类型:
--
作者:
Runnebohm, Avery M;Indovina, Christopher J;Turk, Samantha M;Bailey, Connor G;Orchard, Cade J;Wade, Lauren;Overton, Danielle L;Snow, Brian J;Rubenstein, Eric M

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持续参与内质网(ER)转座的蛋白质被多种转座质量控制(TQC)机制降解。在酿酒酵母中,模型translocon相关蛋白Deg 1-Sec 62受到Hrd 1泛素连接酶的ER相关降解(ERAD),并在较小程度上受到Ste 24蛋白酶介导的蛋白水解。在最近的一次筛选中,我们确定了9个蛋氨酸生物合成基因作为候选TQC监管机构。在这里,我们发现甲硫氨酸限制会损害Hrd 1非依赖性Deg 1-Sec 62降解。除了揭示甲硫氨酸作为一种新的TQC调节剂,我们的研究结果敦促谨慎与营养缺陷型突变的实验室酵母菌株,通常假定不影响细胞过程中的调查。
Proteins that persistently engage endoplasmic reticulum (ER) translocons are degraded by multiple translocon quality control (TQC) mechanisms. In Saccharomyces cerevisiae , the model translocon-associated protein Deg1 -Sec62 is subject to ER-associated degradation (ERAD) by the Hrd1 ubiquitin ligase and, to a lesser extent, proteolysis mediated by the Ste24 protease. In a recent screen, we identified nine methionine-biosynthetic genes as candidate TQC regulators. Here, we found methionine restriction impairs Hrd1-independent Deg1 -Sec62 degradation. Beyond revealing methionine as a novel regulator of TQC, our results urge caution when working with laboratory yeast strains with auxotrophic mutations, often presumed not to influence cellular processes under investigation.