The ins and outs of APC and beta-catenin nuclear transport.
Adenomatous polyposis coli (APC) and beta-catenin, two key interacting proteins implicated in development and cancer, were recently found to traffic into and out of the nucleus in response to internal and external signals. The two proteins can enter and exit the nucleus independently, a discovery that has prompted debate about the previously proposed role of APC as a beta-catenin chaperone. Here, we review the regulation of APC and beta-catenin subcellular localization, in particular in cancer cells. We speculate that, in non-stimulated cells, APC actively exports beta-catenin from the nucleus to the cytoplasm where its levels are regulated by degradation; and, conversely, that, in cancer cells or those stimulated by Wnt signaling, beta-catenin degradation is inhibited and the accruing protein is capable of moving between the nucleus and cytoplasm independently of APC. Models that link APC and beta-catenin transport to function are discussed.
Henderson
Beric R
BR
Westmead Institute for Cancer Research, University of Sydney, Westmead Millennium Institute, NSW, Australia. beric_henderson@wmi.usyd.edu.au
Fagotto
Francois
F
D021581:Active Transport, Cell Nucleus; D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin; D000097606:Exportin 1 Protein
D025601:Adenomatous Polyposis Coli Protein; D003598:Cytoskeletal Proteins; D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D051176:beta Catenin; D000097606:Exportin 1 Protein; C495270:CTNNB1 protein, human