Diacylglycerol kinase α suppresses tumor necrosis factor-α- -induced apoptosis of human melanoma cells through NF-κB activation
Diacylglycerol kinase α suppresses tumor necrosis factor-α- -induced apoptosis of human melanoma cells through NF-κB activation
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DOI：
10.1016/j.bbalip.2006.12.008
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发表时间：
2007-04-01
影响因子：
4.8
通讯作者：
Sakane, Fumio
中科院分区：
文献类型：
--
作者：
Yanagisawa, Kenji;Yasuda, Satoshi;Sakane, Fumio
我们研究了黑色素瘤细胞中二酰基甘油激酶（DGK）a（I型亚型）的意义，因为我们发现这种DGK亚型在几种人黑色素瘤细胞系中表达，但在非癌性黑色素细胞中不表达。有趣的是，野生型（WT）DGK α的过表达，而不是其激酶死亡（KD）突变体的过表达，显著抑制了肿瘤坏死因子（TNF）-α诱导的阿基人黑色素瘤细胞凋亡。在反向实验中，siRNA介导的DGK α敲低显著增强了细胞凋亡。另一方面，其他I型亚型（DGK-beta和DGK-gamma）的过表达对细胞凋亡没有可检测的影响。这些结果表明，DGK α通过其催化作用特异性抑制TNF-α诱导的细胞凋亡。我们发现DGK α-WT的过表达，而不是DGK α-KD的过表达，进一步增强了TNF-α刺激的抗凋亡因子NF-κ B的转录活性。相反，DGK α-敲低显著抑制NF-κ B活性。此外，NF-κ B抑制剂减弱了DGK α过表达的抗凋亡作用。总之，这些结果有力地表明，DGK α是一种新的NF-κ B B，抑制TNF-α诱导的黑色素瘤细胞凋亡的正调控因子。(C)2007 Elsevier B. V.保留所有权利。
We investigated the implication of diacylglycerol kinase (DGK) a (type I isoform) in melanoma cells because we found that this DGK isoform was expressed in several human melanoma cell lines but not in noncancerous melanocytes. Intriguingly, the overexpression of wild-type (WT) DGK alpha, but not of its kinase-dead (KD) mutant, markedly suppressed tumor necrosis factor (TNF)-alpha-induced apoptosis of AKI human melanoma cells. In the reverse experiment, siRNA-mediated knockdown of DGK alpha significantly enhanced the apoptosis. The overexpression of other type I isoforms (DGK beta and DGK-gamma) had, on the other hand, no detectable effects on the apoptosis. These results indicate that DGK alpha specifically suppresses the TNF-alpha-induced apoptosis through its catalytic action. We found that the overexpression of DGK alpha-WT, but not of DGK alpha-KD, further enhanced the TNF-alpha-stimulated transcriptional activity of an anti-apoptotic factor, NF-kappa B. Conversely, DGK alpha-knockdown considerably inhibited the NF-kappa B activity. Moreover, an NF-kappa B inhibitor blunted the anti-apoptotic effect of DGK alpha overexpression. Together, these results strongly suggest that DGK alpha is a novel positive regulator of NF-kappa B, which suppresses TNF-alpha-induced melanoma cell apoptosis. (C) 2007 Elsevier B.V. All rights reserved.