Mayer R J, Arnold J, László L, Landon M, Lowe J
Department of Biochemistry, University of Nottingham Medical School, Queens Medical Centre, U.K.
Biochim Biophys Acta. 1991 Jun 13;1089(2):141-57. doi: 10.1016/0167-4781(91)90002-4.
Studies in recent years have shown that ubiquitin has increasingly important functions in eukaryotic cells; roles which were previously not suspected in healthy and diseased cells. The interplay between molecular pathological and molecular cell biological findings has indicated that ubiquitin may be pivotal in the cell stress response in chronic degenerative and viral diseases. Furthermore, the studies have led to the notion that ubiquitination may not only serve as a signal for nonlysosomal protein degradation but may be a unifying covalent protein modification for the major intracellular protein catabolic systems; these can act to identify proteins for cytosolic proteinases or direct intact and fragmented proteins into the lysosome system for breakdown to amino acids. This unifying role could explain why ubiquitin is restricted to eukaryotic cells, which possess extensive endomembrane systems in addition to a nuclear envelope. Protein ubiquitination is a feature of most filamentous inclusions and certain other intracellular conglomerates that are found in some degenerative and viral diseases. The detection of ubiquitin-protein conjugates is not of great diagnostic importance in these diseases. Protein ubiquitination is not only essential for the normal physiological turnover of proteins but appears to have been adapted as part of an intracellular surveillance system that can be activated by altered, damaged, or foreign proteins and organelles. The purpose of this system is to isolate and eliminate these noxious structures from the cell: as a cytoprotective mechanism this appears to have evolved in the cell akin perhaps to an 'intracellular immune system'. Other heat shock proteins such as hsp 70 may be involved in this process. It is apparent that ubiquitin has a role in embryonic development. Protein ubiquitination is presumably involved in the reorganisation of cytoplasm that accompanies cell differentiation. Ubiquitin is also necessary for the gross intracellular degradative processes which are consequent upon programmed cell death. Cell elimination is of key importance for a number of developmental morphogenetic changes. An understanding of the molecular details of these processes will no doubt provide further insights into the wide ranging roles of ubiquitin in the life process. As it says in the book 'Ubiquitin'; there is no doubt that ubiquitin is a 'lucky' protein. It is lucky in many ways: lucky for scientific progress, lucky for biomedical scientists and lucky for life! If you have not already done so, why don't you get lucky and look for a role for ubiquitin in your experimental system. As Avram Hershko has said "there is plenty to go round"!
近年来的研究表明，泛素在真核细胞中具有越来越重要的功能；这些功能在健康细胞和患病细胞中以前并未被怀疑。分子病理学和分子细胞生物学研究结果之间的相互作用表明，泛素可能在慢性退行性疾病和病毒性疾病的细胞应激反应中起关键作用。此外，这些研究还得出了这样的观点，即泛素化不仅可能作为非溶酶体蛋白降解的信号，而且可能是主要细胞内蛋白分解代谢系统的一种统一的共价蛋白修饰；这些系统可以识别胞质蛋白酶作用的蛋白质，或将完整的和片段化的蛋白质直接导入溶酶体系统分解为氨基酸。这种统一作用可以解释为什么泛素仅限于真核细胞，真核细胞除了有核膜外还拥有广泛的内膜系统。蛋白质泛素化是大多数丝状包涵体以及在一些退行性疾病和病毒性疾病中发现的某些其他细胞内聚集体的一个特征。在这些疾病中，泛素 - 蛋白质缀合物的检测在诊断上并不具有重要意义。蛋白质泛素化不仅对蛋白质的正常生理周转至关重要，而且似乎已被用作细胞内监测系统的一部分，该系统可以被改变的、受损的或外来的蛋白质及细胞器激活。这个系统的目的是从细胞中分离并消除这些有害结构：作为一种细胞保护机制，这似乎是在细胞中进化而来的，类似于一种“细胞内免疫系统”。其他热休克蛋白，如热休克蛋白70，可能也参与了这个过程。显然，泛素在胚胎发育中起作用。蛋白质泛素化大概参与了伴随细胞分化的细胞质重组。泛素对于程序性细胞死亡后随之而来的总体细胞内降解过程也是必需的。细胞清除对于许多发育形态发生变化至关重要。对这些过程分子细节的理解无疑将进一步深入了解泛素在生命过程中的广泛作用。正如《泛素》一书中所说；毫无疑问，泛素是一种“幸运”的蛋白质。它在很多方面都很幸运：对科学进步来说幸运，对生物医学科学家来说幸运，对生命来说幸运！如果你还没有这样做，为什么不走运一下，在你的实验系统中寻找泛素的作用呢。正如阿夫拉姆·赫什科所说“机会很多”！
