Regulated protein denitrosylation by cytosolic and mitochondrial thioredoxins.
Published
Journal Article
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.
Full Text
Duke Authors
Cited Authors
- Benhar, M; Forrester, MT; Hess, DT; Stamler, JS
Published Date
- May 23, 2008
Published In
Volume / Issue
- 320 / 5879
Start / End Page
- 1050 - 1054
PubMed ID
- 18497292
Pubmed Central ID
- 18497292
Electronic International Standard Serial Number (EISSN)
- 1095-9203
Digital Object Identifier (DOI)
- 10.1126/science.1158265
Language
- eng
Conference Location
- United States