Conformational selection
Conformational selection
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发表时间：
2013
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通讯作者：
A. Heinrichs
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作者：
A. Heinrichs
[13] Arianne海因里希斯、Beth Moorefield和Stéphane Larochelle的研究结果比单独使用SUMO或泛素的结果高80倍。泛素和SUMO信号在体内通过RNF 4整合，RNF 4是一种产生杂合链的SUMO靶向E3连接酶。内源性RNF 4在电离辐射处理后定位于DNA修复灶，并且当RNF 4被siRNA耗尽时，RAP 80和BRCA 1的募集减少。转染RNF 4野生型构建体，而不是RING结构域突变体，恢复RAP 80和BRCA 1募集到耗尽细胞中的DSB，这表明RNF 4泛素化活性是产生RAP 80结合信号所必需的。这些结果确立了泛素和SUMO在调节BRCA 1定位于DNA断裂中的作用，并为研究SUMO-泛素杂合链在信号细胞应激中的潜在作用提供了基础。（Sci.信号了5，ra 88，2012）BM构象选择
13 Written by Arianne Heinrichs, Beth Moorefield & Stéphane Larochelle 80-fold greater than that observed for either SUMO or ubiquitin alone. Ubiquitin and SUMO signals are integrated in vivo by RNF4, a SUMOtargeted E3 ligase that generates hybrid chains. Endogenous RNF4 localizes to DNA-repair foci upon ionizing-radiation treatment, and recruitment of both RAP80 and BRCA1 is reduced when RNF4 is depleted by siRNA. Transfection of an RNF4 wild-type construct, but not a RING-domain mutant, restores RAP80 and BRCA1 recruitment to DSBs in depleted cells, which indicates that RNF4 ubiquitination activity is required to generate RAP80 binding signals. These results establish roles for both ubiquitin and SUMO in regulating BRCA1 localization to DNA breaks and provide a foundation to investigate the potential roles of SUMO-ubiquitin hybrid chains in signaling cell stress. (Sci. Signal. 5, ra88, 2012) BM Conformational selection