cAMP response element-binding protein interacts with the homeodomain protein Cdx2 and enhances transcriptional activity

Cdx-2 encodes for a homeodomain protein that is expressed in intestinal epi thelial cells. The Cdx2 protein triggers intestinal differentiation in cell lines and is necessary for maintenance of the intestinal phenotype in mice . CBP (cAMP response element-binding protein) is a transcriptional co-activ ator that interacts with many transcription factors and components of the b asal transcriptional machinery. In this study, we demonstrate that CBP is m arkedly induced upon differentiation of the Caco-2 intestinal cell line and augments Cdx2-dependent transcriptional activity. Cdx2 interacts with the amino-terminal domain of CBP, and the two proteins coexist in vivo within t he same nuclear protein complex. Moreover, expression of the CBP domain tha t interacts with Cdx2 acts as a dominant-negative inhibitor of transcriptio nal activation by Cdx2. These findings demonstrate a direct interaction bet ween an intestinal homeodomain protein and CBP and suggest that CBP partici pates in the network of transcriptional proteins that direct intestinal dif ferentiation.