S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding
S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding
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DOI：
10.1038/ncb1268
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发表时间：
2005-07-01
影响因子：
21.3
通讯作者：
Sawa, A
中科院分区：
文献类型：
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作者：
Hara, MR;Agrawal, N;Sawa, A
甘油醛-3-磷酸脱氢酶（GAPDH）影响细胞毒性，在细胞凋亡过程中易位到细胞核。在这里，我们报告了一个信号通路，其中一氧化氮（NO）的产生，随后凋亡刺激eliminates S-亚硝基化的GAPDH，触发结合Siah 1（E3泛素连接酶），核转位和凋亡。GAPDH的S-亚硝基化增强了其与Siah 1的结合，Siah 1的核定位信号介导GAPDH的易位。GAPDH稳定Siah 1，促进其降解核蛋白。内毒素对巨噬细胞的激活和谷氨酸对神经元的激活导致GAPDH-Siah 1结合、核转位和凋亡，而NO缺失可阻止这些。NO-S-亚硝基化GAPDH-Siah 1级联反应可能是细胞毒作用的重要分子机制.
Glyceraldehyde- 3- phosphate dehydrogenase ( GAPDH) influences cytotoxicity, translocating to the nucleus during apoptosis. Here we report a signalling pathway in which nitric oxide ( NO) generation that follows apoptotic stimulation elicits S- nitrosylation of GAPDH, which triggers binding to Siah1 ( an E3 ubiquitin ligase), nuclear translocation and apoptosis. S- nitrosylation of GAPDH augments its binding to Siah1, whose nuclear localization signal mediates translocation of GAPDH. GAPDH stabilizes Siah1, facilitating its degradation of nuclear proteins. Activation of macrophages by endotoxin and of neurons by glutamate elicits GAPDH - Siah1 binding, nuclear translocation and apoptosis, which are prevented by NO deletion. The NO - S- nitrosylation GAPDH - Siah1 cascade may represent an important molecular mechanism of cytotoxicity.