Transcriptional activation by NF-kappa B requires multiple coactivators

Nuclear factor-kappa B (NF-kappa B) plays a role in the transcriptional reg ulation of genes involved in inflammation and cell survival. In this report we demonstrate that NF-kappa B recruits a coactivator complex that has str iking similarities to that recruited by nuclear receptors. Inactivation of either cyclic AMP response element binding protein (CREB)-binding protein ( CBP), members of the p160 family of coactivators, or the CBP-associated fac tor (p/CAF) by nuclear antibody microinjection prevents NF-kappa B-dependen t transactivation. Like nuclear receptor-dependent gene expression, NF-kapp a B-dependent gene expression requires specific LXXLL motifs in one of the p160 family members, and enhancement of NF-kappa B activity requires the hi stone acetyltransferase (HAT) activity of p/CAF but not that of CBP. This c oactivator complex is differentially recruited by members of the Rel family . The p50 homodimer fails to recruit coactivators, although the p50-p65 het erodimeric form of the transcription factor assembles the integrator comple x. These findings provide new mechanistic insights into how this family of dimeric transcription factors has a differential effect on gene expression.