Diacylglycerol kinase α suppresses tumor necrosis factor-α-induced apoptosis of human melanoma cells through NF-κB activation
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- 作者：Kenji Yanagisawa ; Satoshi Yasuda ; Masahiro Kai ; Shin-ichi Imai ; Keiko Yamada ; Toshiharu Yamashita ; Kowichi Jimbow ; Hideo Kanoh ; Fumio Sakane
- 关键词：Diacylglycerol kinase ; Apoptosis ; Tumor necrosis factor-α ; NF-κ ; B ; Melanoma
- 刊名：Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids
- 出版年：2007
- 出版时间：April 2007
- 年：2007
- 卷：1771
- 期：4
- 页码：462-474
- 全文大小：964 K
文摘
We investigated the implication of diacylglycerol kinase (DGK) α (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) DGKα, but not of its kinase-dead (KD) mutant, markedly suppressed tumor necrosis factor (TNF)-α-induced apoptosis of AKI human melanoma cells. In the reverse experiment, siRNA-mediated knockdown of DGKα significantly enhanced the apoptosis. The overexpression of other type I isoforms (DGKβ and DGKγ) had, on the other hand, no detectable effects on the apoptosis. These results indicate that DGKα specifically suppresses the TNF-α-induced apoptosis through its catalytic action. We found that the overexpression of DGKα-WT, but not of DGKα-KD, further enhanced the TNF-α-stimulated transcriptional activity of an anti-apoptotic factor, NF-κB. Conversely, DGKα-knockdown considerably inhibited the NF-κB activity. Moreover, an NF-κB inhibitor blunted the anti-apoptotic effect of DGKα overexpression. Together, these results strongly suggest that DGKα is a novel positive regulator of NF-κB, which suppresses TNF-α-induced melanoma cell apoptosis.