TAFII105 mediates activation of anti-apoptotic genes by NF-kappaB.
The transcription factor NF-kappaB is important for expression of genes involved in immune responses, viral infections, cytokine signaling and stress. In addition NF-kappaB 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 TAFII105 is essential ... for activation of anti-apoptotic genes in response to TNF-alpha, serving as a transcriptional coactivator for NF-kappaB. The putative coactivator domain of TAFII105 interacts with the activation domain of the p65/RelA member of the NF-kappaB family, and further stimulates p65-induced transcription in human 293 cells. Moreover, inhibition of TAFII105 activity by overexpression of a dominant negative mutant of TAFII105 decreased NF-kappaB transcriptional activity and severely reduced cell survival in response to TNF-alpha. Similarly, expression of anti-sense TAFII105 RNA sensitized the cells to TNF-alpha cytotoxicity. These results suggest that TAFII105 is involved in activation of anti-apoptotic genes by NF-kappaB.
Mesh Terms:
Apoptosis, DNA-Binding Proteins, Gene Expression Regulation, Humans, Mutation, NF-kappa B, Protein Binding, TATA-Binding Protein Associated Factors, Transcription Factor RelA, Transcription Factor TFIID, Transcription Factors, Transcription Factors, TFII, Transcription, Genetic, Tumor Necrosis Factor-alpha
Apoptosis, DNA-Binding Proteins, Gene Expression Regulation, Humans, Mutation, NF-kappa B, Protein Binding, TATA-Binding Protein Associated Factors, Transcription Factor RelA, Transcription Factor TFIID, Transcription Factors, Transcription Factors, TFII, Transcription, Genetic, Tumor Necrosis Factor-alpha
EMBO J.
Date: Sep. 01, 1998
PubMed ID: 9724652
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