TAF sub(II)105 mediates activation of anti- apoptotic genes by NF- mu B

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