The functionally conserved proteins CBP and p300 act in conjunction with other factors to activate transcription of DNA. A new factor, p/CIP, has been discovered that is present in the cell as a complex with CEP and is required for transcriptional activity of nuclear receptors and other CBP/p300-dependent transcription factors. The highly related nuclear-receptor co-activator protein NCoA-1 is also specifically required for ligand-dependent activation of genes by nuclear receptors, p/CIP, NCoA-1 and CBP all contain related leucine-rich charged helical interaction motifs that ape required for receptor-specific mechanisms of gene activation, and allow the selective inhibition of distinct signal-transduction pathways.