Fas-induced caspase denitrosylation

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-nitrosy lated on their catalytic-site cysteine in unstimulated human cell Lines and denitrosylated upon activation of the Fas apoptotic pathway. Decreased cas pase-3 S-nitrosylation was associated with an increase in intracellular cas pase activity. Fas therefore activates caspase-3 not only by inducing the c leavage of the caspase zymogen to its active subunits, but also by stimulat ing the denitrosylation of its active-site thiol. Protein S-nitrosylation/d enitrosylation can thus serve as a regulatory process in signal transductio n pathways.