Mechanisms of protein degradation - An odyssey with ODC
Mechanisms of protein degradation - An odyssey with ODC
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DOI：
10.4161/cc.4.11.2115
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发表时间：
2005-11-01
期刊：
影响因子：
4.3
通讯作者：
Shaul, Y
中科院分区：
文献类型：
--
作者：
Kahana, C;Asher, G;Shaul, Y
细胞内蛋白水解在调节细胞周期、免疫和炎症反应、发育、分化和转化等基本细胞过程中起重要作用。泛素-蛋白酶体系统负责大部分细胞短寿命蛋白的降解。该系统涉及多个泛素残基与靶蛋白的缀合及其通过多聚泛素链被26 S蛋白酶体识别。对鸟氨酸脱羧酶（ODC）降解的研究表明，多聚泛素不是26 S蛋白酶体识别的唯一信号。26 S蛋白酶体对ODC的识别是通过与多胺诱导的蛋白质（称为抗酶（Az））相互作用介导的。虽然ODC的降解是不依赖于泛素的，但其调节剂Az和抗酶抑制剂（AzI）（一种调节Az可用性的ODC同源蛋白）的降解是依赖于泛素的。有趣的是，ODC经历了另一种类型的泛素不依赖性降解的20 S蛋白酶体，这是由NAD（P）H醌氧化还原酶1（NQO 1）调节。考虑到泛素系统在细胞蛋白质降解过程中的普遍性，一种关键的细胞酶受到两种不同的蛋白水解途径的影响，这是相当值得注意的，这两种不同的蛋白水解途径不同于泛素依赖的途径。ODC的这种特殊行为为我们提供了关于蛋白质降解的有价值的见解。
Intracellular proteolysis plays an important role in regulating fundamental cellular processes such as cell cycle, immune and inflammation responses, development, differentiation, and transformation. The ubiquitin-proteasome system accounts for the degradation of the majority of cellular short-lived proteins. This system involves the conjugation of multiple ubiquitin residues to the target protein and its recognition by the 26S proteasome through the poly-ubiquitin chain. Studies on the degradation of ornithine decarboxylase (ODC) demonstrated that poly-ubiquitin is not the only signal recognized by the 26S proteasome. The recognition of ODC by the 26S proteasome is mediated by interaction with a polyamine-induced protein termed, antizyme (Az). While the degradation of ODC is ubiquitin-independent, the degradation of its regulator Az, and of antizyme-inhibitor (AzI), an ODC homologous protein that regulates Az availability, are ubiquitin dependent. Interestingly, ODC undergoes another type of ubiquitin-independent degradation by the 20S proteasome that is regulated by NAD(P) H quinone oxidoreductase 1 (NQO1). Considering the prevalence of the ubiquitin system in the process of cellular protein degradation it is rather remarkable that a key cellular enzyme is subjected to two different proteolytic pathways that are different from the ubiquitin dependent one. This exceptional behavior of ODC provides us with valuable insights regarding protein degradation in general.