Aging is not associated with proteasome impairment in UPS reporter mice.
Aging is not associated with proteasome impairment in UPS reporter mice.
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DOI：
10.1371/journal.pone.0005888
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发表时间：
2009-06-11
期刊：
影响因子：
3.7
通讯作者：
Petrucelli L
中科院分区：
文献类型：
--
作者：
Cook C;Gass J;Dunmore J;Tong J;Taylor J;Eriksen J;McGowan E;Lewis J;Johnston J;Petrucelli L
泛素的共价连接调节泛素-蛋白酶体系统 (UPS) 的功能并最终调节许多蛋白质的降解。鉴于其在蛋白质调节中的重要作用，即使 UPS 活性的轻微扰动也会严重损害细胞功能。我们已经生成并表征了一种新型转基因小鼠模型，该模型表达了先前描述的 UPS 功能报告基因。该 UPS 报告基因包含附加到绿色荧光蛋白 C 末端的降解决定子序列，并且主要在我们的转基因模型的整个大脑的神经元中表达。然后我们证明该报告系统对体内 UPS 抑制敏感。考虑到评估大脑中蛋白酶体功能的相关障碍，我们的小鼠模型独特地提供了实时监测复杂生物体单个神经元中 UPS 功能的能力。我们的新型小鼠模型现在提供了有用的资源，可用于评估衰老的影响以及神经退行性疾病的各种遗传和/或药理学修饰剂。
Covalent linkage of ubiquitin regulates the function and, ultimately, the degradation of many proteins by the ubiquitin-proteasome system (UPS). Given its essential role in protein regulation, even slight perturbations in UPS activity can substantially impair cellular function. We have generated and characterized a novel transgenic mouse model which expresses a previously described reporter for UPS function. This UPS reporter contains a degron sequence attached to the C-terminus of green fluorescent protein, and is predominantly expressed in neurons throughout the brain of our transgenic model. We then demonstrated that this reporter system is sensitive to UPS inhibition in vivo. Given the obstacles associated with evaluating proteasomal function in the brain, our mouse model uniquely provides the capability to monitor UPS function in real time in individual neurons of a complex organism. Our novel mouse model now provides a useful resource with which to evaluate the impact of aging, as well as various genetic and/or pharmacological modifiers of neurodegenerative disease(s).
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