Characterization of the Novel DNA-Binding Activity of p270, a hSWI/SNF Protein Frequently Downregulated in Breast Cancer

摘要

Human SWI/SNF complexes are ATP-dependent chromatin remodelers that play fundamental roles in the regulation of cell growth, development and tumor suppression. p270 is an integral member of these complexes and is absent in approximately 10% of breast tumors. The ARID region is the most prominent motif of the p270 protein and it is important for the function of the protein in vitro. This suggests that this region has an important role in the tumor suppressor function of p270. The ARID is a DNA-binding motif that is diagnostic of a family of proteins that are important in development, tissue specific gene expression and tumorigenesis. My studies therefore concentrated on the ARID- dependent DNA-binding properties of p270. Through a combination of structural, biochemical and mutational approaches, valuable data about the structural integrity of the domain and its interaction with DNA have emerged. This biochemical information can be important for drug design or the development of diagnostic/prognostic tools in breast cancer. Furthermore, this biochemical analysis will be a very useful tool in the literature for future studies on the physiological role of p270 and its tumor suppressor functions in the human SWI/SNF complexes.