Protein ubiquitination: a regulatory post-translational modification.
Protein ubiquitination: a regulatory post-translational modification.
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发表时间：
1987-10
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通讯作者：
Wilkinson Kd
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作者：
Wilkinson Kd
泛素与多种细胞蛋白的共价连接（泛素化）是真核细胞中常见的翻译后修饰。关于这些修饰在正常或病理状态下的功能知之甚少。本文就泛素化在细胞核、细胞质和质膜上的特点进行了综述和讨论。还报道了代谢泛素的酶的研究，使用泛素依赖的蛋白水解系统作为模型。已经从牛胸腺中部分纯化了四种特异性识别泛蛋白并水解泛蛋白羧基末端衍生物的酶。这些是含巯基的蛋白酶，其也将从泛素-蛋白质缀合物释放泛素。细胞质中存在这些解偶联酶和蛋白酶表明在蛋白水解和解偶联之间存在偶联物的分配。为了研究决定蛋白质水解与去缀合的相对速率的因素，我们开发了一种合成大量纯泛素-蛋白质缀合物的通用方法。通过化学修饰泛素并检测其在蛋白质降解系统中的活性，探讨了泛素的结构/功能关系。这些研究已经鉴定了被蛋白水解系统的酶识别的泛素分子的区域，确立了该分子可以被改变并用作此类系统的探针，并且将指导定点突变体泛素的设计，以便更充分地限定泛素分子上的识别位点。这些类型的研究可能会导致适当的泛素功能所需的分子相互作用的理解，并允许药物的设计，这可能是有用的理解泛素化的作用及其在正常和病理状态的重要性。
The covalent attachment of ubiquitin to a variety of cellular proteins (ubiquitination) is a common post-translational modification in eukaryotic cells. Little is known about the function of these modifications in either the normal or the pathological state. The characteristics of ubiquitination in the nucleus, the cytoplasm, and on the plasma membrane are reviewed and discussed here. Also reported are studies on the enzymes which metabolize ubiquitin, using the ubiquitin-dependent proteolysis system as a model. Four enzymes which specifically recognize ubiquitin and hydrolyze carboxyl-terminal derivatives of ubiquitin have been partially purified from bovine thymus. These are thiol-containing proteases which will also release ubiquitin from ubiquitin-protein conjugates. The presence of these deconjugating enzymes and the proteases in the cytoplasm suggests that there is a partition of conjugates between proteolysis and deconjugation. To study the factors which determine the relative rates of proteolysis versus deconjugation, we have developed a general method of synthesizing large amounts of pure ubiquitin-protein conjugates. The structure/function relationships of ubiquitin have been probed by chemically modifying ubiquitin and examining its activity in the protein degradation system. These studies have identified regions of the ubiquitin molecule which are recognized by the enzymes of the proteolysis system, established that the molecule can be altered and used as a probe of such systems and will guide the design of site-directed mutant ubiquitins in order to more fully define the recognition sites on the ubiquitin molecule. It is likely that studies of these types will lead to an understanding of the molecular interactions required for proper ubiquitin function and allow design of drugs which could be useful in understanding the role of ubiquitination and its importance in normal and pathological states.