A protective role for the human SMG-1 kinase against tumor necrosis factor-α-induced apoptosis
A protective role for the human SMG-1 kinase against tumor necrosis factor-α-induced apoptosis
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DOI：
10.1074/jbc.m708008200
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发表时间：
2008-05-09
影响因子：
4.8
通讯作者：
Abraham, Robert T.
中科院分区：
文献类型：
--
作者：
Oliveira, Vasco;Romanow, William J.;Abraham, Robert T.
人类生殖器形态发生抑制因子-1（hSMG-1）蛋白激酶在人类细胞的mRNA监测和遗传毒性应激反应途径中起双重作用。在这里，我们报告说，人U2 OS骨肉瘤细胞中小干扰RNA介导的hSMG-1（而不是ATM、ATR、hUpf 1或hUpf 2）缺失显着增加了肿瘤坏死因子-α（TNF-α）刺激诱导的细胞凋亡的幅度并加速了细胞凋亡的速率。在hSMG-1耗竭细胞中观察到的TNF α介导的细胞杀伤增加与无义介导的mRNA衰减抑制或TNF α诱导的NF-κ B活化抑制无关。相反，我们观察到hSMG-1的缺失加速了长型FLICE抑制蛋白（FLIPL）的降解，FLIPL是TNF α处理细胞中诱导死亡信号复合物介导的caspase-8活化的抑制剂。这些结果表明，hSMG-1在TNF α诱导的应激期间的细胞存活中起重要作用。
The human suppressor of morphogenesis in genitalia-1 (hSMG-1) protein kinase plays dual roles in mRNA surveillance and genotoxic stress response pathways in human cells. Here, we report that small interfering RNA-mediated depletion of hSMG-1, but not ATM, ATR, hUpf1, or hUpf2, in human U2OS osteosarcoma cells markedly increases the magnitude and accelerates the rate of apoptosis induced by tumor necrosis factor-alpha(TNF alpha) stimulation. The increase in TNF alpha-mediated cell killing observed in hSMG-1-depleted cells is not related to the suppression of nonsense-mediated mRNA decay or to the inhibition of TNF alpha-induced NF-kappa B activation. Rather, we observed that loss of hSMG-1 accelerates the degradation of the long form of the FLICE-inhibitory protein (FLIPL), an inhibitor of death-inducing signaling complex-mediated caspase-8 activation, in TNF alpha-treated cells. These results suggest that hSMG-1 plays an important role in cell survival during TNF alpha-induced stress.