Substoichiometric hydroxynonenylation of a single protein recapitulates whole-cell-stimulated antioxidant response.

Substoichiometric hydroxynonenylation of a single protein recapitulates whole-cell-stimulated antioxidant response.
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DOI:
10.1021/ja5084249
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发表时间:
2015-01-14
影响因子:
15
通讯作者:
Aye, Yimon
Aye, Yimon
中科院分区:
化学1区
文献类型:
--
作者:
Parvez, Saba;Fu, Yuan;Li, Jiayang;Long, Marcus J. C.;Lin, Hong-Yu;Lee, Dustin K.;Hu, Gene S.;Aye, Yimon

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Lipid-derived electrophiles (LDEs) that can directly modify proteins have emerged as important small-molecule cues in cellular decision-making. However, because these diffusible LDEs can modify many targets [e.g., >700 cysteines are modified by the well-known LDE 4-hydroxynonenal (HNE)], establishing the functional consequences of LDE modification on individual targets remains devilishly difficult. Whether LDE modifications on a single protein are biologically sufficient to activate discrete redox signaling response downstream also remains untested. Herein, using T-REX (targetable reactive electrophiles and oxidants), an approach aimed at selectively flipping a single redox switch in cells at a precise time, we show that a modest level (∼34%) of HNEylation on a single target is sufficient to elicit the pharmaceutically important antioxidant response element (ARE) activation, and the resultant strength of ARE induction recapitulates that observed from whole-cell electrophilic perturbation. These data provide the first evidence that single-target LDE modifications are important individual events in mammalian physiology.
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发表时间: 2009-04
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影响因子: --
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