Sci. Signal., 27 May 2008
Cell Biology Regulating S-Nitrosylation
L. Bryan Ray
Science, Science Signaling, AAAS, Washington, DC 20005, USA
Covalent modification of proteins by S-nitrosylation is an important mechanism for regulation of biochemical activity in cells. However, mechanisms of protein denitrosylation have not been well characterized. The protease caspase-3, which promotes apoptosis, is inhibited by S-nitrosylation and is denitrosylated in cells in which the cell death-promoting receptor Fas is activated. Benhar et al. (see the Perspective by Holmgren) purified a protein fraction that catalyzed denitrosylation of caspase-3 and identified thioredoxin-1 (Trx1) as the protein most likely to be responsible for the denitrosylation activity. Depletion of Trx1 caused accumulation of S-nitrosylated caspase-3 and other S-nitrosylated proteins in cultured cells, and Fas-induced denitrosylation of caspase-3 was inhibited by depleting thioredoxin reductase 2. Thus, regulated denitrosylation of target proteins by Trx1 appears to provide a key component of enzymatic regulation of caspase-3 and possibly other proteins by S-nitrosylation.
Citation: L. B. Ray, Regulating S-Nitrosylation. Sci. Signal. 1, ec202 (2008).
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