Fas-induced caspase denitrosylation
Fas-induced caspase denitrosylation
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DOI：
10.1126/science.284.5414.651
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发表时间：
1999-04-23
期刊：
影响因子：
56.9
通讯作者：
Stamler, JS
中科院分区：
文献类型：
--
作者：
Mannick, JB;Hausladen, A;Stamler, JS
只有少数细胞内S-亚硝基化蛋白已被确定，它是未知的，如果蛋白S-亚硝基化/脱亚硝基化是一个组成部分的信号转导级联。在未受刺激的人细胞系中，发现Caspase-3酶原在其催化位点半胱氨酸上被S-亚硝基化，并在Fas凋亡途径激活后被脱亚硝基化。caspase-3 S-亚硝基化的减少与细胞内caspase活性的增加有关。因此，Fas不仅通过诱导半胱天冬酶酶原裂解成其活性亚基，而且通过刺激其活性位点巯基的脱亚硝基化来激活半胱天冬酶-3。因此，蛋白质S-亚硝基化/脱亚硝基化可以作为信号转导途径中的调节过程。
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.