Evidence that de novo protein synthesis is dispensable for anti-apoptotic effects of NF-κB

The transcription factor NF-kappa B is a positive transcription factor for a number of genes and has been recognized as an anti-apoptotic regulator. However, the mechanism by which NF-kappa B blocks apoptosis is still controversial. Here, we demonstrate the evidence that NF-kappa B could attenuate the TNF-alpha-induced apoptosis without de novo protein synthesis using human pancreatic cancer cell lines, MIA PaCa-2 and Capan-2, The TNF-alpha-induced apoptosis was blocked by IL-1 beta, a potent inducer of NF-kappa B activation. This inhibitory effect of IL-1 beta was evident when cells were treated with protein synthesis inhibitors such as cycloheximide (CHS). Moreover, NF-kappa B decoy oligonucleotides could not block the anti-apoptotic effect of IL-1 beta at doses sufficient to block the NF-kappa B-dependent transcription induced by IL-1 beta, To confirm the role of NF-kappa B in blocking apoptosis we generated stable cell Lines expressing I kappa B Delta N, a highly stable form of I kappa B alpha, a cytoplasmic inhibitor of NF-kappa B. In these stable transfectants, the antiapoptotic effect of IL-1 beta was totally abolished, indicating that the anti-apoptotic action of IL-1 beta could be ascribed to the NF-kappa B action. These findings show that ne novo protein synthesis is dispensable for anti-apoptotic effects of NF-kappa B and support the possibility that NF-kappa B could exert its anti-apoptotic action through protein-protein interaction.