The N-end rule pathway controls the import of peptides through degradation of a transcriptional repressor
The N-end rule pathway controls the import of peptides through degradation of a transcriptional repressor
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DOI：
10.1093/emboj/17.1.269
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发表时间：
1998-01-02
期刊：
影响因子：
11.4
通讯作者：
Varshavsky, A
中科院分区：
文献类型：
--
作者：
Byrd, C;Turner, GC;Varshavsky, A
泛素依赖的蛋白水解系统是细胞周期、细胞分化和应激反应等过程的基础。其中一个系统是N-末端规则途径，它靶向具有不稳定N-末端残基的蛋白质。本文报道了该途径的主要识别组分Ubr 1 p通过降解35 kDa同源域蛋白Cup 9 p调节酿酒酵母中的肽输入，我们发现Cup 9 p是一种短寿命的蛋白质（t（1/2）α类似于5 min），其降解需要Ubr 1 p，Cup 9 p作为PTR 2的阻遏物，PTR 2是编码跨膜肽转运蛋白的基因。与Ubr 1 p通过其不稳定的N-末端残基识别的工程N-末端规则底物相反，Ubr 1 p通过内部降解信号靶向Cup 9 p。Ubr 1 p-Cup 9 p-Ptr 2 p回路是第一个由N端规则途径控制的生理过程的例子。啤酒。因此，N-末端规则途径的一种生理底物既作为肽输入的阻遏物又作为铜稳态的调节物。
Ubiquitin-dependent proteolytic systems underlie many processes, including the cell cycle, cell differentiation and responses to stress, One such system is the N-end rule pathway, which targets proteins bearing destabilizing N-terminal residues, Here we report that Ubr1p, the main recognition component of this pathway, regulates peptide import in the yeast Saccharomyces cerevisiae through degradation of Cup9p, a 35 kDa homeodomain protein, Cup9p was identified using a screen for mutants that bypass the previously observed requirement for Ubr1p in peptide import, We show that Cup9p is a short-lived protein (t(1/2) Alpha similar to 5 min) whose degradation requires Ubr1p, Cup9p acts as a repressor of PTR2, a gene encoding the transmembrane peptide transporter. In contrast to engineered N-end rule substrates, which are recognized by Ubr1p through their destabilizing N-terminal residues, Cup9p is targeted by Ubr1p through an internal degradation signal. The Ubr1p-Cup9p-Ptr2p circuit is the first example of a physiological process controlled by the N-end rule pathway, An earlier study identified Cup9p as a protein required for an aspect of resistance to copper toxicity in S. cerevisiae. Thus, one physiological substrate of the N-end rule pathway functions as both a repressor of peptide import and a regulator of copper homeostasis.