CBP and p300 are transcriptional coactivators of p65, a component of the NF-κB family. The study shows that CBP and p300 enhance p65-dependent transcription of genes like E-selectin and VCAM-1. Both proteins interact with the transcriptional activation domain of p65, as demonstrated by mammalian two-hybrid assays, GST binding, and coimmunoprecipitation. The adenovirus E1A protein, which binds to CBP and p300, inhibits p65-dependent gene expression, but this inhibition can be reversed by overexpressing CBP or p300. These findings suggest that CBP and p300 play a crucial role in NF-κB-mediated gene activation, particularly in cytokine-induced immune and inflammatory responses. The interaction between CBP/p300 and p65 is essential for transcriptional activation, and these coactivators may integrate diverse signaling pathways to regulate gene expression. The study also highlights the importance of CBP and p300 in the regulation of inflammatory genes, such as E-selectin, which is involved in leukocyte rolling and immune responses. The results indicate that CBP and p300 are present in limited amounts and that their availability influences the efficiency of p65-dependent transcription. The study provides insights into the molecular mechanisms underlying NF-κB activation and its role in inflammatory processes.CBP and p300 are transcriptional coactivators of p65, a component of the NF-κB family. The study shows that CBP and p300 enhance p65-dependent transcription of genes like E-selectin and VCAM-1. Both proteins interact with the transcriptional activation domain of p65, as demonstrated by mammalian two-hybrid assays, GST binding, and coimmunoprecipitation. The adenovirus E1A protein, which binds to CBP and p300, inhibits p65-dependent gene expression, but this inhibition can be reversed by overexpressing CBP or p300. These findings suggest that CBP and p300 play a crucial role in NF-κB-mediated gene activation, particularly in cytokine-induced immune and inflammatory responses. The interaction between CBP/p300 and p65 is essential for transcriptional activation, and these coactivators may integrate diverse signaling pathways to regulate gene expression. The study also highlights the importance of CBP and p300 in the regulation of inflammatory genes, such as E-selectin, which is involved in leukocyte rolling and immune responses. The results indicate that CBP and p300 are present in limited amounts and that their availability influences the efficiency of p65-dependent transcription. The study provides insights into the molecular mechanisms underlying NF-κB activation and its role in inflammatory processes.