Degradation of proteins from the ER of S-cerevisiae requires an intact unfolded protein response pathway
Degradation of proteins from the ER of S-cerevisiae requires an intact unfolded protein response pathway
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DOI：
10.1016/s1097-2765(00)80251-8
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发表时间：
2000-04-01
期刊：
影响因子：
16
通讯作者：
Ploegh, H
中科院分区：
文献类型：
--
作者：
Casagrande, R;Stern, P;Ploegh, H
为了分析内质网对膜蛋白降解的需求，我们在酵母中表达了小鼠主要组织相容性复合体I类重链H-2K(B)。像其他从内质网降解的蛋白质一样，未组装的H-2K(B)重链不被运输到高尔基体，而是以蛋白酶体依赖的方式降解。H-2K(B)重链的过表达诱导了未折叠蛋白反应(UPR)。在不能装载UPR的酵母突变株中，H-2K(B)重链非常稳定。这种降解缺陷被Hac1p的活性形式的表达抑制，Hac1p是一种转录因子，上调UPR诱导的基因。这些结果表明，内质网中蛋白质底物的降解需要UPR的诱导。
To dissect the requirements of membrane protein degradation from the ER, we expressed the mouse major histocompatibility complex class I heavy chain H-2K(b) in yeast. Like other proteins degraded from the ER, unassembled H-2K(b) heavy chains are not transported to the Golgi but are degraded in a proteasome-dependent manner. The overexpression of H-2K(b) heavy chains induces the unfolded protein response (UPR). In yeast mutants unable to mount the UPR, H-2K(b) heavy chains are greatly stabilized. This defect in degradation is suppressed by the expression of the active form of Hac1p, the transcription factor that upregulates UPR-induced genes. These results indicate that induction of the UPR is required for the degradation of protein substrates from the ER.