Wnt signaling and APC

Wnt signals are one of the five signal transduction pathways that shape virtually all cell fates and which are inappropriately activated in most solid tumors.  The key regulated effector of Wnt signaling is the protein ß-catenin.  Wnt signaling acts by regulating its stability.  In the absence of Wnt signaling, ß-catenin is targeted for proteasomal destruction by a multi-protein complex called the destruction complex.  In the presence of Wnt signals, the destruction complex is
inactivated, and ß-catenin levels rise, allowing it to enter the nucleus and work with TCF proteins to regulate Wnt target genes.  In our lab, we seek to determine how the tumor suppressor APC, a key component of the destruction complex, regulates both Wnt signaling and the cytoskeleton.  We use both the fruit fly Drosophila and cultured human colon culture cells to unravel the mechanisms by which APC works.  We combine powerful
genetic tools and state of the art microscopy.  We are currently exploring how APC regulates assembly and disassembly of the destruction complex as part of a catalytic cycle.  We are also exploring separate roles APC plays in regulating the cytoskeleton and thus ensures high fidelity chromosome segregation. Finally, we explore novel biological roles for Wnt signaling during development.

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