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Science. 2008 May 23;320(5879):1050-4. doi: 10.1126/science.1158265.

Regulated protein denitrosylation by cytosolic and mitochondrial thioredoxins.

Author information

1
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.

Abstract

Nitric oxide acts substantially in cellular signal transduction through stimulus-coupled S-nitrosylation of cysteine residues. The mechanisms that might subserve protein denitrosylation in cellular signaling remain uncharacterized. Our search for denitrosylase activities focused on caspase-3, an exemplar of stimulus-dependent denitrosylation, and identified thioredoxin and thioredoxin reductase in a biochemical screen. In resting human lymphocytes, thioredoxin-1 actively denitrosylated cytosolic caspase-3 and thereby maintained a low steady-state amount of S-nitrosylation. Upon stimulation of Fas, thioredoxin-2 mediated denitrosylation of mitochondria-associated caspase-3, a process required for caspase-3 activation, and promoted apoptosis. Inhibition of thioredoxin-thioredoxin reductases enabled identification of additional substrates subject to endogenous S-nitrosylation. Thus, specific enzymatic mechanisms may regulate basal and stimulus-induced denitrosylation in mammalian cells.

Comment in

PMID:
18497292
PMCID:
PMC2754768
DOI:
10.1126/science.1158265
[Indexed for MEDLINE]
Free PMC Article

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