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.
Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
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Yamit-Hezi
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Dikstein
D017209:Apoptosis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding; D035381:TATA-Binding Protein Associated Factors; D051996:Transcription Factor RelA; D035362:Transcription Factor TFIID; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D019473:Transcription Factors, TFII / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004268:DNA-Binding Proteins; D016328:NF-kappa B; C101881:TAF4B protein, human; D035381:TATA-Binding Protein Associated Factors; D051996:Transcription Factor RelA; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D014409:Tumor Necrosis Factor-alpha