TAF(II)105 MEDIATES ACTIVATION OF ANTI-APOPTOTIC GENES BY NF-KAPPA-B

The transcription factor NF-kappa B is important for expression of gen es 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 activati ng anti-apoptotic genes. Here we report that the substoichiometric TFI ID subunit TAF(II)105 is essential for activation of anti-apoptotic ge nes in response to TNF-alpha, serving as a transcriptional coactivator for NF-kappa B. The putative coactivator domain of TAF(II)105 interac ts 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(II)105 activity by overexpression of a dominant negative mutant of TAF(II)105 decreased NF-kappa B trans criptional activity and severely reduced cell survival in response to TNF-alpha. Similarly, expression of anti-sense TAF(II)105 RNA sensitiz ed the cells to TNF-alpha cytotoxicity. These results suggest that TAF (II)105 is involved in activation of anti-apoptotic genes by NF-kappa B.