Lindsten Kristina, Dantuma Nico P
Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Ageing Res Rev. 2003 Oct;2(4):433-49. doi: 10.1016/s1568-1637(03)00031-x.
Controlled proteolysis of regulatory or aberrant proteins by the ubiquitin/proteasome system is indispensable for cell viability. Conformational diseases such as Alzheimer's, Parkinson's and Huntington's disease are characterised by the accumulation of misfolded or aggregation-prone proteins. Since these proteins are typical substrates of the ubiquitin/proteasome system, it is not surprising that various models propose impairment of this system as a contributing factor to the pathology of conformational disorders. The complex nature of the ubiquitin/proteasome system and its universal role in cell physiology however turns evaluation of these attractive hypotheses into a major challenge. Several reporter substrates for the ubiquitin/proteasome system have recently been developed to facilitate functional studies of the system in living cells. In this review, we will discuss these new tools as well as the proteins associated with conformational disease that have been studied with these reporters.
泛素/蛋白酶体系统对调节性或异常蛋白质的可控蛋白水解对于细胞活力不可或缺。诸如阿尔茨海默病、帕金森病和亨廷顿病等构象疾病的特征在于错误折叠或易于聚集的蛋白质的积累。由于这些蛋白质是泛素/蛋白酶体系统的典型底物，因此各种模型提出该系统的损伤是构象障碍病理学的一个促成因素也就不足为奇了。然而，泛素/蛋白酶体系统的复杂性质及其在细胞生理学中的普遍作用使得对这些有吸引力的假说进行评估成为一项重大挑战。最近已经开发了几种用于泛素/蛋白酶体系统的报告底物，以促进该系统在活细胞中的功能研究。在这篇综述中，我们将讨论这些新工具以及使用这些报告物研究的与构象疾病相关的蛋白质。
