The subcellular destinations of apc proteins

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Abstract
APC proteins are well-conserved antagonists of canonical Wnt signalling with crucial functions in normal and malignant development. The classical function of APC proteins is to promote the destabilization of β-catenin–Armadillo in the cytoplasm, probably by binding to the Axin destruction complex. A highly conserved nuclear-export function of APC proteins seems to be crucial for their ability to downregulate the activity of nuclear β-catenin–Armadillo. APC proteins are also associated with the plasma membrane of epithelial cells where they ensure the maintainance of adherens junctions and, perhaps indirectly, the orientation of mitotic spindles in the epithelial plane. The ability of APC to cluster at growing microtubule plus ends might affect the migratory behaviour of motile cells. Chromosomal non-disjunction might result from a failure of mutant APC to bind to microtubule plus ends of mitotic spindles which, in turn, might cause a failure of microtubule capture by kinetochores or by the cell cortex. The shuttling of APC between the different subcellular compartments and its control vary between different cell types and states. The ultimate question is whether APC proteins have a single molecular function that underlies its many cellular functions — which are apparently disparate from each other — and manifest themselves in various biological contexts.