Fas-induced caspase denitrosylation

JB Mannick, A Hausladen, L Liu, DT Hess, M Zeng… - Science, 1999 - science.org
JB Mannick, A Hausladen, L Liu, DT Hess, M Zeng, QX Miao, LS Kane, AJ Gow, JS Stamler
Science, 1999science.org
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 …
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.
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