WNT TARGET GENE REGULATION BY BETA-CATENIN AND THE APC TUMOR SUPPRESSOR

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The LEF-1/TCF DNA-binding proteins mediate Wnt/Wg signaling events that regulate cell proliferation, organogenesis, and self-renewal of intestinal epithelial progenitor and stem cells. Aberrant regulation of the Wnt pathway plays a key role in many cancers. For example, nearly 85% of human colorectal cancers contain mutations in the tumor suppressor adenomatous polyposis coli protein (APC), which controls the stability and nuclear accumulation of the LEF-1 transcriptional co-activator, beta-catenin. Our goal is to characterize the mechanism of beta-catenin:LEF-1 activation and transcriptional repression by the APC tumor suppressor.