Diacylglycerol kinase alpha suppresses tumor necrosis factor-alpha-induced apoptosis of human melanoma cells through NF-kappaB activation

Biochim Biophys Acta. 2007 Apr;1771(4):462-74. doi: 10.1016/j.bbalip.2006.12.008. Epub 2007 Jan 8.


We investigated the implication of diacylglycerol kinase (DGK) alpha (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) DGKalpha, 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 DGKalpha significantly enhanced the apoptosis. The overexpression of other type I isoforms (DGKbeta and DGKgamma) had, on the other hand, no detectable effects on the apoptosis. These results indicate that DGKalpha specifically suppresses the TNF-alpha-induced apoptosis through its catalytic action. We found that the overexpression of DGKalpha-WT, but not of DGKalpha-KD, further enhanced the TNF-alpha-stimulated transcriptional activity of an anti-apoptotic factor, NF-kappaB. Conversely, DGKalpha-knockdown considerably inhibited the NF-kappaB activity. Moreover, an NF-kappaB inhibitor blunted the anti-apoptotic effect of DGKalpha overexpression. Together, these results strongly suggest that DGKalpha is a novel positive regulator of NF-kappaB, which suppresses TNF-alpha-induced melanoma cell apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Diacylglycerol Kinase / metabolism*
  • Humans
  • Isoenzymes / metabolism
  • Melanocytes / drug effects
  • Melanocytes / enzymology
  • Melanoma / enzymology*
  • Melanoma / pathology*
  • NF-kappa B / metabolism*
  • Protein Transport / drug effects
  • RNA, Small Interfering / metabolism
  • Rats
  • Swine
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Isoenzymes
  • NF-kappa B
  • RNA, Small Interfering
  • Tumor Necrosis Factor-alpha
  • Diacylglycerol Kinase