Harnessing the ubiquitination machinery to target the degradation of specific cellular proteins
Harnessing the ubiquitination machinery to target the degradation of specific cellular proteins
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DOI：
10.1016/s1097-2765(00)00074-5
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发表时间：
2000-09-01
期刊：
影响因子：
16
通讯作者：
Howley, PM
中科院分区：
文献类型：
--
作者：
Zhou, PB;Bogacki, R;Howley, PM
特定基因或其蛋白质产物的功能表征通常依赖于评估其消除的后果，通常通过基因敲除、核酶、反义或RNA介导的干扰（RNAi）技术来完成。细胞蛋白质的选择性降解主要由泛素-蛋白酶体途径介导。操纵的泛素依赖性蛋白水解机制，以消除特定的基因产物在蛋白质水平上已经尝试了一些成功的体外，然而，这种方法的体内疗效尚未实现。在这里，我们报告成功的工程底物受体的一个主要的泛素蛋白水解机器，以指导在酵母和哺乳动物细胞中的稳定的细胞蛋白质的降解。
The functional characterization of a specific gene, or its protein product, often relies on assessing the consequences of its elimination, usually accomplished by gene knockout, ribozyme, antisense, or RNA-mediated interference (RNAi) technologies. The selective degradation of cellular proteins is mediated primarily by the ubiquitin-proteasome pathway. Manipulation of the ubiquitin-dependent proteolytic machinery to eliminate specific gene products at the protein level has been previously attempted with some success in vitro; however, the in vivo efficacy of this approach has not yet been achieved. Here we report successful engineering of the substrate receptor of a major ubiquitin-proteolytic machinery to direct the degradation of otherwise stable cellular proteins both in yeast and in mammalian cells.