Interaction of TAF(II)105 with selected p65/Rela dimers is associated with activation of subset of NF-κB genes

Abstract

TAF(II)105, a substoichiometric coactivator subunit of TFIID, is important for activation of anti-apoptotic genes by NF-κB in response to the cytokine tumor necrosis factor (TNF)-α. 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-KB. 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-α. Analysis of the interaction between TAF(II)105 and different NF- κB complexes has revealed substantial differences in the affinity of TAF(II)105 toward different p65/RelA-containing dimers. We have identified the TNF-α induced antiapoptotic A20 gene as a target gene of TAF(II)105. A20 has a differential protective effect on cell death induced by TNF-α in the presence of either the dominant negative mutant of TAF(II)105 (TAF(II)105ΔC) or the superdominant IκBα. The results suggest that the inhibitory effect of TAF(II)105ΔC on NF-κB-dependent genes is restricted to a subset of anti- apoptotic genes while the effect of IκBα is more general. Thus, an interaction between NF-κB and a specific coactivator is important for specifying target gene activation.