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-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.
Mannick
J B
JB
Department of Adult Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA. joan_mannick@dfci.harvard.edu
Hausladen
A
A
Liu
L
L
Hess
D T
DT
Zeng
M
M
Miao
Q X
QX
Kane
L S
LS
Gow
A J
AJ
Stamler
J S
JS
D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D003545:Cysteine / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D008623:Mercaptoethanol; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000378:metabolism; D009603:Nitroso Compounds / Q000378:metabolism; D026403:S-Nitrosothiols; D015398:Signal Transduction; D019014:fas Receptor / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D009573:Nitrites; D009603:Nitroso Compounds; D026403:S-Nitrosothiols; D019014:fas Receptor; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D008623:Mercaptoethanol; C032635:S-nitrosomercaptoethanol; D019001:Nitric Oxide Synthase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003545:Cysteine