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S-Nitrosylation
''S''-Nitrosylation specifically attaches to a thiol group to form an ''S''-nitrosothiol (SNO). Where the thiol group belongs to a subset of specific cysteine residues in proteins, the resulting SNO is an ''S''-nitrosoprotein. ''S''-Nitrosylation is a form of post-translational protein modification with similarities to phosphorylation.〔Anand P, Stamler JS. J. Mol. Med. (Berl). 90(3): 233-244 (2012)〕 ''S''-Nitrosylation meets the criteria for validation as a signaling mechanism in that it is stimulus evoked,〔Hoffmann, J, Dimmeler, S, Haendeler, J. FEBS Lett. 551:153-158 (2003)〕 precisely targeted,〔Sun JH, Xin CL, Eu JP, Stamler JS, Meissner G. Proc. Natl. Acad. Sci. U S A 98:11158-11162 (2003)〕 reversible,〔Padgett CM, Whorton AR. Am. J. Physiol. 269:739-749 (1995)〕 spatiotemporally restricted〔Fang M, Jaffrey SR, Sawa A, Ye K, Luo X, Snyder SH. Neuron 28:183-193 (2000)〕〔Iwakiri Y, Satoh A, Chatterjee S, Toomre DK, Chalouni CM, Fulton D, Groszmann RJ, Shah VH, Sessa WC. Proc. Natl. Acad. Sci. U S A 103:19777-19782 (2006)〕 and necessary for specific cell responses.〔Hess DT, Matsumoto A, Kim SO, Marshall HE, Stamler JS. Nat. Rev. Mol. Cell. Biol. 6:150-166 (2005)〕 The first protein whose activity was shown to be regulated by ''S''-nitrosylation in this fashion was the NMDA-type glutamate receptor in the brain.〔Lei SZ, Pan Z-H, Aggarwal SK, Chen H-SV, Hartman J, Sucher NJ, Lipton SA. Neuron 8(6):1087-1099 (1992)〕〔Lipton SA, Choi Y-B, Pan Z-H, Lei SZ, Chen H-SV, Sucher NJ, Singel DJ, Loscalzo J, Stamler JS. Nature 364(6438):626-632 (1993)〕 ''S''-Nitrosylation has since been shown to be ubiquitous in biology, having been demonstrated to occur in all phylogenetic Kingdoms〔Seth D, Hausladen A, Wang YJ, Stamler JS. Science 336(6080):470-473 (2012)〕〔Malik SI, Hussain A, Yun BW, Spoel SH, Loake GJ. Plant Sci. 181(5):540-544 (2011)〕 and has been described as the prototypic redox-based signalling mechanism,〔Stamler JS, Lamas S, Fang FC. Cell 106(6):675-683 (2001)〕 hypothesized to have evolved on primordial Earth.〔Derakhshan B, Hao G, Gross SS. Cardiovasc. Res. 75(2):210-219 (2007)〕
The reverse process of ''S''-nitrosylation is termed denitrosylation, which in addition to occurring spontaneously in the presence of metal ions and under conditions of photolysis,〔Singh RJ, Hogg N, Joseph J, Kalyanaraman B. J. Biol. Chem. 271(31):18596-603 (1996)〕 has recently been demonstrated to be an enzymically controlled process. ''S''-Nitrosoglutathione reductase (GSNOR), which accelerates the decomposition of ''S''-nitrosoglutathione (GSNO) and other SNO-proteins, is an alcohol dehydrogenase class III isoenzyme which has been shown to be conserved from bacteria to humans.〔Liu L, Hausladen A, Zeng M, Que L, Heitman J, Stamler JS. Nature 410(6827):490-4 (2001)〕 Similarly, the thioredoxin/thioredoxin reductase system catalyzes the denitrosylation of a number of ''S''-nitrosoproteins〔Stoyanovsky DA, Tyurina YY, Tyurin VA, Anand D, Mandavia DN, Gius D, Ivanova J, Pitt B, Billiar TR, Kagan VE. J. Am. Chem. Soc. 127:15815-23 (2005)〕〔Sengupta R, Ryter SW, Zuckerbraun BS, Tzeng E, Billiar TR, Stoyanovsky DA. Biochemistry. 46:8472-83 (2007)〕〔Benhar M, Forrester MT, Hess DT, Stamler JS. Science 320:1050-4 (2008)〕 Aberrant or dysregulated denitrosylation or ''S''-nitrosylation has been associated with stroke (cerebral ischemia)〔Gu Z, Kaul M, Yan B, Kridel SJ, Cui J, Strongin A, Smith JW, Liddington RC, Lipton SA. Science 297(5584):1186-90 (2002)〕 and a number of chronic degenerative diseases, including Parkinson's and Alzheimer's disease〔Yao D, Gu Z, Nakamura T, Shi Z-Q, Ma Y, Gaston B, Palmer LA, Rockenstein EM, Zhang Z, Masliah E, Uehara T, Lipton SA. Proc. Natl. Acad. Sci. U S A 101(29):10810-4 (2004)〕〔Uehara T, Nakamura T, Yao D, Shi Z-Q, Gu Z, Masliah E, Nomura Y, Lipton SA. Nature 2441(7092):513-7 (2006)〕〔Benhar M, Forrester MT, Stamler JS. ACS Chem. Biol. 1(6):355-8 (2006)〕〔Cho D-H, Nakamura T, Fang J, Cieplak P, Godzik A, Gu Z, Lipton SA. Science 324(5923):102-5 (2009)〕 and Amyotrophic Lateral Sclerosis (ALS).〔Schonhoff CM, Matsuoka M, Tummala H, Johnson MA, Estevéz AG, Wu R, Kamaid A, Ricart KC, Hashimoto Y, Gaston B, Macdonald TL, Xu Z, Mannick JB. Proc. Natl. Acad. Sci. U S A 103(7):2404-9 (2006)〕 There is an emerging role of ''S''-nitrosylation in cancer biology.〔Aranda E, López-Pedrera C, De La Haba-Rodriguez JR, Rodriguez-Ariza A. Curr. Mol. Med. 12(1):50-67 (2012)〕 ''S''-Nitrosylation of EGFR and Src activates an oncogenic signaling network in human basal-like breast cancer 〔 Switzer CH, Glynn SA, Cheng RY, Ridnour LA, Green JE, Ambs S, Wink DA. Mol Cancer Res.Sep;10(9):1203-15.(2012) 〕
== References ==
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