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