Abstract
Only a few intracellular S-nitrosylated proteins have been identified, and it is unknown if protein S-nitrosylation/denitrosylation is a component of signal transduction cascades. Caspase-3 zymogens were found to be S-nitrosylated on their catalytic-site cysteine in unstimulated human cell lines and denitrosylated upon activation of the Fas apoptotic pathway. Decreased caspase-3 S-nitrosylation was associated with an increase in intracellular caspase activity. Fas therefore activates caspase-3 not only by inducing the cleavage of the caspase zymogen to its active subunits, but also by stimulating the denitrosylation of its active-site thiol. Protein S-nitrosylation/denitrosylation can thus serve as a regulatory process in signal transduction pathways.
Publication types
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, P.H.S.
MeSH terms
- Animals
- Apoptosis
- Binding Sites
- Caspase 3
- Caspases / metabolism*
- Cell Line
- Cysteine / metabolism*
- Enzyme Activation
- Enzyme Inhibitors / pharmacology
- Enzyme Precursors / metabolism
- Humans
- Mercaptoethanol*
- Nitric Oxide / metabolism*
- Nitric Oxide Synthase / antagonists & inhibitors
- Nitrites / metabolism
- Nitroso Compounds / metabolism
- S-Nitrosothiols*
- Signal Transduction
- fas Receptor / physiology*
- omega-N-Methylarginine / pharmacology
Substances
- Enzyme Inhibitors
- Enzyme Precursors
- Nitrites
- Nitroso Compounds
- S-Nitrosothiols
- fas Receptor
- omega-N-Methylarginine
- Nitric Oxide
- Mercaptoethanol
- S-nitrosomercaptoethanol
- Nitric Oxide Synthase
- CASP3 protein, human
- Caspase 3
- Caspases
- Cysteine