Regulating S-Nitrosylation

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Science  23 May 2008:
Vol. 320, Issue 5879, pp. 981
DOI: 10.1126/science.320.5879.981c

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. (p. 1050; 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.

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