Substoichiometric Hydroxynonenylation of a Single Protein Recapitulates Whole-Cell-Stimulated Antioxidant Response
In: Journal of the American Chemical Society, Jg. 137 (2014-12-31), S. 10-13
Online
unknown
Zugriff:
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.
Titel: |
Substoichiometric Hydroxynonenylation of a Single Protein Recapitulates Whole-Cell-Stimulated Antioxidant Response
|
---|---|
Autor/in / Beteiligte Person: | Aye, Yimon ; Lin, Hongyu ; Hu, Gene S. ; Parvez, Saba ; Fu, Yuan ; Long, Marcus J. C. ; Lee, Dustin K. ; Li, Jiayang |
Link: | |
Zeitschrift: | Journal of the American Chemical Society, Jg. 137 (2014-12-31), S. 10-13 |
Veröffentlichung: | American Chemical Society (ACS), 2014 |
Medientyp: | unknown |
ISSN: | 1520-5126 (print) ; 0002-7863 (print) |
DOI: | 10.1021/ja5084249 |
Schlagwort: |
|
Sonstiges: |
|