Evidence against Stable Protein S-Nitrosylation as a Widespread Mechanism of Post-translational Regulation
| العنوان: | Evidence against Stable Protein S-Nitrosylation as a Widespread Mechanism of Post-translational Regulation |
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| المؤلفون: | Wolhuter, Kathryn, Whitwell, Harry J, Switzer, Christopher H, Burgoyne, Joseph R, Timms, John F, Eaton, Philip |
| المصدر: | 450.e5 Molecular Cell Wolhuter, K, Whitwell, H J, Switzer, C H, Burgoyne, J R, Timms, J F & Eaton, P 2018, ' Evidence against Stable Protein S-Nitrosylation as a Widespread Mechanism of Post-translational Regulation ', MOLECULAR CELL, vol. 69, no. 3, pp. 438-450.e5 . https://doi.org/10.1016/j.molcel.2017.12.019Test |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Proteomics, Biochemistry & Molecular Biology, PTEN, Nitrosation, OXIDATION, Nitric Oxide, Article, Humans, Cysteine, Disulfides, Sulfhydryl Compounds, NITRIC-OXIDE SYNTHASE, Science & Technology, S-Nitrosothiols, thiol, Proteins, Cell Biology, 11 Medical And Health Sciences, S-nitrosation, 06 Biological Sciences, NITROSOHEMOGLOBIN, S-nitrosylation, NITROSOTHIOLS, redox, Proteolysis, OXYR, protein, signaling, Life Sciences & Biomedicine, Oxidation-Reduction, Protein Processing, Post-Translational, SYSTEM, disulfide, Developmental Biology |
| الوصف: | Summary 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. Graphical Abstract Highlights • Protein S-nitrosation is commonly regarded as a stable, regulatory modification • However, S-nitrosothiols are labile and rapidly react with thiols to form disulfides • Here disulfides are shown to be the dominant end effectors of nitrosative signaling • Protein S-nitrosation as a regulatory end effector may occur, but this may be rare Nitric oxide-related molecules post-translationally modify protein thiols, resulting in functional changes. Such S-nitrosothiols are widely thought to be regulatory end effector modifications. However, Wolhuter et al. show that S-nitrosation predominantly serves as a transient intermediate in the formation of disulfide bonds. This furthers our understanding of how nitric oxide regulates signaling. |
| وصف الملف: | application/pdf |
| تدمد: | 1097-4164 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::e479f28b2f275428850d1a62306f0db2Test https://pubmed.ncbi.nlm.nih.gov/29395059Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid.dedup....e479f28b2f275428850d1a62306f0db2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10974164 |
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