HRD gene dependence of endoplasmic reticulum-associated degradation.
HRD gene dependence of endoplasmic reticulum-associated degradation.
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内质网相关降解的 HRD 基因依赖性。
DOI：
10.1091/mbc.11.5.1697
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发表时间：
2000
影响因子：
3.3
通讯作者：
Hampton,R
中科院分区：
文献类型：
--
作者：
Wilhovsky,S;Gardner,R;Hampton,R
几个实验室的工作表明，许多不同的蛋白质都受到内质网（ER）的共同降解机制的影响。这一机制包括内质网膜蛋白Hrd1p/Der3p和Hrd3p以及内质网相关的泛素偶联酶Ubc7p和Ubc6p。这一降解途径的底物种类繁多，导致了一个合理的假设，即hrd （Hmg辅酶a还原酶降解）基因编码的蛋白质通常参与真核生物内质网蛋白的降解。我们通过直接比较各种内质网膜蛋白内质网相关降解的hr依赖性来测试该模型。我们的数据表明，hrdgenes在蛋白质降解中的作用，即使是在这一高度定义的蛋白质子集中，也可以从绝对依赖到完全独立。因此，er相关的降解可以通过不涉及Hrd1p或Hrd3p的机制发生，尽管它们明显具有广泛的底物包膜。这些数据支持hrdgene编码蛋白作为特异性因子（如泛素连接酶）功能的模型，而不是作为参与内质网降解的常见方面的因素。
Work from several laboratories has indicated that many different proteins are subject to endoplasmic reticulum (ER) degradation by a common ER-associated machinery. This machinery includes ER membrane proteins Hrd1p/Der3p and Hrd3p and the ER-associated ubiquitin-conjugating enzymes Ubc7p and Ubc6p. The wide variety of substrates for this degradation pathway has led to the reasonable hypothesis that theHRD(Hmg CoA reductase degradation) gene-encoded proteins are generally involved in ER protein degradation in eukaryotes. We have tested this model by directly comparing theHRDdependency of the ER-associated degradation for various ER membrane proteins. Our data indicated that the role ofHRDgenes in protein degradation, even in this highly defined subset of proteins, can vary from absolute dependence to complete independence. Thus, ER-associated degradation can occur by mechanisms that do not involve Hrd1p or Hrd3p, despite their apparently broad envelope of substrates. These data favor models in which theHRDgene-encoded proteins function as specificity factors, such as ubiquitin ligases, rather than as factors involved in common aspects of ER degradation.