1. Fas-induced caspase denitrosylation.
- Author
-
Mannick JB, Hausladen A, Liu L, Hess DT, Zeng M, Miao QX, Kane LS, Gow AJ, and Stamler JS
- Subjects
- Animals, Apoptosis, Binding Sites, Caspase 3, Cell Line, Enzyme Activation, Enzyme Inhibitors pharmacology, Enzyme Precursors metabolism, Humans, Nitric Oxide Synthase antagonists & inhibitors, Nitrites metabolism, Nitroso Compounds metabolism, Signal Transduction, omega-N-Methylarginine pharmacology, Caspases metabolism, Cysteine metabolism, Mercaptoethanol, Nitric Oxide metabolism, S-Nitrosothiols, fas Receptor physiology
- 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.
- Published
- 1999
- Full Text
- View/download PDF