TAF(II)105 mediates activation of anti-apoptotic genes by NF-κB

Abstract

The transcription factor NF-κB is important for expression of genes involved in immune responses, viral infections, cytokine signaling and stress. In addition NF-κB plays a crucial role in protecting cells from TNF-α-induced apoptotic stimuli, presumably by activating anti-apoptotic genes. Here we report that the substoichiometric TFIID subunit TAF(II)105 is essential for activation of anti-apoptotic genes in response to TNF-α, serving as a transcriptional coactivator for NF-κB. The putative coactivator domain of TAF(II)105 interacts with the activation domain of the p65/RelA member of the NF-κB family, and further stimulates p65-induced transcription in human 293 cells. Moreover, inhibition of TAF(II)105 activity by overexpression of a dominant negative mutant of TAF(II)105 decreased NF-κB transcriptional activity and severely reduced cell survival in response to TNF-α. Similarly, expression of anti-sense TAF(II)105 RNA sensitized the cells to TNF-α cytotoxicity. These results suggest that TAF(II)105 is involved in activation of anti-apoptotic genes by NF-κB.