NF-≃B antiapoptosis: Induction of TRAF1 and TRAF2 and c-IAP1 and c- IAP2 to suppress caspase-8 activation

Abstract

Tumor necrosis factor α (TNF-α) binding to the TNF receptor (TNFR) potentially initiates apoptosis and activates the transcription factor nuclear factor kappa B (NF-≃B), which suppresses apoptosis by an unknown mechanism. The activation of NF-≃B was found to block the activation of caspase-8. TRAF1 (TNFR-associated factor 1), TRAF2, and the inhibitor-of- apoptosis (IAP) proteins c-IAP1 and c-IAP2 were identified as gene targets of NF-≃B transcriptional activity. In cells in which NF-≃B was inactive, all of these proteins were required to fully suppress. TNF-induced apoptosis, whereas c-IAP1 and c-IAP2 were sufficient to suppress etoposide-induced apoptosis. Thus, NF-≃B activates a group of gene products that function cooperatively at the earliest checkpoint to suppress TNF-α-mediated apoptosis and that function more distally to suppress genotoxic agent- mediated apoptosis.