Global functional map of the p23 molecular chaperone reveals an extensive cellular network.

Global functional map of the p23 molecular chaperone reveals an extensive cellular network.
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DOI:
10.1016/j.molcel.2011.05.029
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发表时间:
2011-07-22
期刊:
影响因子:
16
通讯作者:
Freeman BC
Freeman BC
中科院分区:
生物学1区
文献类型:
--
作者:
Echtenkamp FJ;Zelin E;Oxelmark E;Woo JI;Andrews BJ;Garabedian M;Freeman BC

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随着进化的发展,Hsp90分子伴侣系统从一个简单的原核因子转变为一个包括各种辅伴侣的扩展网络。我们已经采取了高通量的基因组和蛋白质组学方法来更好地了解丰富的酵母p23辅伴侣Sba1。我们的工作揭示了一个意想不到的p23网络,它显示出相当独立于已知的Hsp90客户。此外,我们的数据揭示了p23广泛的核作用,这与分子伴侣限制胞浆活动的历史教条形成了鲜明对比。验证研究表明,酵母p23是正常高尔基体功能、核糖体生物发生所必需的,也是从广泛的诱变剂中有效修复DNA所必需的。值得注意的是,哺乳动物的p23在这些途径中扮演着保守的角色,并且对于正常的细胞移动是必要的。综上所述,我们的工作表明,p23伴侣服务于一个广泛的生理网络,并与Hsp90结合并独立于Hsp90发挥作用。
In parallel with evolutionary developments, the Hsp90 molecular chaperone system shifted from a simple prokaryotic factor into an expansive network that includes a variety of cochaperones. We have taken high-throughput genomic and proteomic approaches to better understand the abundant yeast p23 cochaperone Sba1. Our work revealed an unexpected p23 network that displayed considerable independence from known Hsp90 clients. Additionally, our data uncovered a broad nuclear role for p23, contrasting with the historical dogma of restricted cytosolic activities for molecular chaperones. Validation studies demonstrated that yeast p23 was required for proper Golgi function, ribosome biogenesis and was necessary for efficient DNA repair from a wide range of mutagens. Notably, mammalian p23 had conserved roles in these pathways as well as being necessary for proper cell mobility. Taken together, our work demonstrates that the p23 chaperone serves a broad physiological network and functions both in conjunction with and sovereign to Hsp90.
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