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Sci. STKE, 5 September 2000 EDITORS' CHOICECANCER APC's NES Helps Shuttle ß-Catenin PDQAbstract: Adenomatous polyposis coli (APC) promotes the degradation of ß-catenin. When APC is mutated, as in colon cancer cells, ß-catenin accumulates in the nucleus, where it functions as a transcriptional coactivator of T-cell factor. The mechanism by which APC regulates ß-catenin degradation has remained elusive. Now, Rosin-Arbesfeld et al. demonstrate that APC contains a functional nuclear export signal (NES), and that APC shuttles ß-catenin into the cytoplasm for subsequent proteasomal degradation. COOH-terminal fragments of APC remained exclusively cytoplasmic. Treatment of APC-expressing cells with leptomycin B, a nuclear export inhibitor, revealed that APC remains in the nucleus, suggesting that an NES exists in the COOH-terminus of APC. The authors observed that ß-catenin colocalized with wild-type APC in the cytoplasm, or in the nucleus with NES-mutated APC. Gene reporter assays also indicated that wild-type APC reduced the ability of ß-catenin to cotransactivate luciferase expression, whereas NES-mutated APC was unable to repress ß-catenin-mediated transcription. Rosin-Arbesfeld, R., Townsley, F., and Bienz, M. (2000) The APC tumour suppressor has a nuclear export function. Nature 406: 1009-1012. [Online Journal]
Citation: APC's NES Helps Shuttle ß-Catenin PDQ. Sci. STKE 2000, tw2 (2000). |
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