Isaksson A, Musti A M, Bohmann D
European Molecular Biology Laboratory, Heidelberg, Germany.
Biochim Biophys Acta. 1996 Aug 8;1288(1):F21-9. doi: 10.1016/0304-419x(96)00011-x.
Since the discovery of ubiquitin-dependent protein degradation almost two decades ago, great strides have been made towards a detailed understanding of the biochemistry of this process (reviewed in [1-3]). It was, however, only in recent years that the physiological role of the ubiquitin system in signal transduction and the regulation of several cell functions started to be appreciated and experimentally addressed. As with other principal mechanisms of signal transduction, such as phosphorylation or GTP hydrolysis, much of the information regarding the role of the ubiquitin system as a component of cell regulation and signaling cascades, was gained in studies of transformation and the control of cell growth. It seems, however, that ubiquitin-dependent proteolysis, and possibly other processes that are controlled by protein ubiquitination, play a role in many aspects of cellular function from the control of differentiation to intracellular trafficking [1,3,4]. Here we will review some of the results that implicate ubiquitin-dependent proteolysis in the control of cell growth and that indicate how perturbations of ubiquitin-dependent degradation of oncogene and tumor suppressor gene products may contribute to cell transformation and oncogenesis.
自从大约二十年前发现泛素依赖性蛋白质降解以来，在详细了解这一过程的生物化学方面已经取得了巨大进展（见[1-3]中的综述）。然而，直到近年来，泛素系统在信号转导以及几种细胞功能调节中的生理作用才开始得到认识并通过实验进行研究。与其他主要的信号转导机制（如磷酸化或GTP水解）一样，关于泛素系统作为细胞调节和信号级联反应组成部分的作用的许多信息，是在转化和细胞生长控制的研究中获得的。然而，似乎泛素依赖性蛋白水解以及可能由蛋白质泛素化控制的其他过程，在从分化控制到细胞内运输的细胞功能的许多方面都发挥着作用[1,3,4]。在这里，我们将综述一些表明泛素依赖性蛋白水解参与细胞生长控制的结果，以及这些结果如何表明癌基因和肿瘤抑制基因产物的泛素依赖性降解的扰动可能导致细胞转化和肿瘤发生。
