Lorentz O, Suh E R, Taylor J K, Boudreau F, Traber P G
Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
J Biol Chem. 1999 Mar 12;274(11):7196-9. doi: 10.1074/jbc.274.11.7196.
Cdx2 encodes for a homeodomain protein that is expressed in intestinal epithelial 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-activator that interacts with many transcription factors and components of the basal transcriptional machinery. In this study, we demonstrate that CBP is markedly 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 the same nuclear protein complex. Moreover, expression of the CBP domain that interacts with Cdx2 acts as a dominant-negative inhibitor of transcriptional activation by Cdx2. These findings demonstrate a direct interaction between an intestinal homeodomain protein and CBP and suggest that CBP participates in the network of transcriptional proteins that direct intestinal differentiation.
Cdx2编码一种在肠上皮细胞中表达的同源结构域蛋白。Cdx2蛋白在细胞系中触发肠分化，并且对于维持小鼠的肠表型是必需的。CBP（环磷酸腺苷反应元件结合蛋白）是一种转录共激活因子，它与许多转录因子和基础转录机制的组分相互作用。在本研究中，我们证明CBP在Caco-2肠细胞系分化时被显著诱导，并增强Cdx2依赖的转录活性。Cdx2与CBP的氨基末端结构域相互作用，并且这两种蛋白在体内存在于同一核蛋白复合物中。此外，与Cdx2相互作用的CBP结构域的表达作为Cdx2转录激活的显性负性抑制剂。这些发现证明了一种肠同源结构域蛋白与CBP之间的直接相互作用，并表明CBP参与了指导肠分化的转录蛋白网络。
