Interaction of TAFII105 with selected p65/RelA dimers is associated with activation of subset of NF-kappa B genes.
TAF(II)105, a substoichiometric coactivator subunit of TFIID, is important for activation of anti-apoptotic genes by NF-kappaB in response to the cytokine tumor necrosis factor (TNF)-alpha. In the present study we have analyzed the mechanism of TAF(II)105 function with respect to its regulation of p65/RelA, a component of NF-kappaB. We found two independent p65/RelA-binding domains within the N terminus of TAF(II)105. One of these domains appears to be crucial for TAF(II)105-mediated anti-apoptotic gene activation in response to TNF-alpha. Analysis of the interaction between TAF(II)105 and different NF-kappaB complexes has revealed substantial differences in the affinity of TAF(II)105 toward different p65/RelA-containing dimers. We have identified the TNF-alpha induced anti-apoptotic A20 gene as a target gene of TAF(II)105. A20 has a differential protective effect on cell death induced by TNF-alpha in the presence of either the dominant negative mutant of TAF(II)105 (TAF(II)105DeltaC) or the superdominant IkappaBalpha. The results suggest that the inhibitory effect of TAF(II)105DeltaC on NF-kappaB-dependent genes is restricted to a subset of anti-apoptotic genes while the effect of IkappaBalpha is more general. Thus, an interaction between NF-kappaB and a specific coactivator is important for specifying target gene activation.
Yamit-Hezi
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A
Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
Nir
S
S
Wolstein
O
O
Dikstein
R
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli; D005786:Gene Expression Regulation; D020672:I-kappa B Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics; D011817:Rabbits; D035381:TATA-Binding Protein Associated Factors; D051996:Transcription Factor RelA; D035362:Transcription Factor TFIID; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; D011506:Proteins; D035381:TATA-Binding Protein Associated Factors; D051996:Transcription Factor RelA; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha