Wolhuter, K;
Whitwell, HJ;
Switzer, CH;
Burgoyne, JR;
Timms, JF;
Eaton, P;
(2018)
Evidence against Stable Protein S-Nitrosylation as a Widespread Mechanism of Post-translational Regulation.
Molecular Cell
, 69
(3)
438-450.e5.
10.1016/j.molcel.2017.12.019.
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Abstract
S-nitrosation, commonly referred to as S-nitrosylation, is widely regarded as a ubiquitous, stable post-translational modification that directly regulates many proteins. Such a widespread role would appear to be incompatible with the inherent lability of the S-nitroso bond, especially its propensity to rapidly react with thiols to generate disulfide bonds. As anticipated, we observed robust and widespread protein S-nitrosation after exposing cells to nitrosocysteine or lipopolysaccharide. Proteins detected using the ascorbate-dependent biotin switch method are typically interpreted to be directly regulated by S-nitrosation. However, these S-nitrosated proteins are shown to predominantly comprise transient intermediates leading to disulfide bond formation. These disulfides are likely to be the dominant end effectors resulting from elevations in nitrosating cellular nitric oxide species. We propose that S-nitrosation primarily serves as a transient intermediate leading to disulfide formation. Overall, we conclude that the current widely held perception that stable S-nitrosation directly regulates the function of many proteins is significantly incorrect.
Type: | Article |
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Title: | Evidence against Stable Protein S-Nitrosylation as a Widespread Mechanism of Post-translational Regulation |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1016/j.molcel.2017.12.019 |
Publisher version: | http://dx.doi.org/10.1016/j.molcel.2017.12.019 |
Language: | English |
Additional information: | © 2017 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | Cell Biology, NITRIC-OXIDE SYNTHASE, NITROSOTHIOLS, OXIDATION, NITROSOHEMOGLOBIN, SYSTEM, PTEN, OXYR, S-nitrosation, S-nitrosylation, disulfide, protein, cysteine, thiol, redox, signaling |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Womens Cancer |
URI: | https://discovery.ucl.ac.uk/id/eprint/10043340 |
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