Editors' ChoiceCancer

APC's NES Helps Shuttle β-Catenin PDQ

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Science's STKE  05 Sep 2000:
Vol. 2000, Issue 48, pp. tw2
DOI: 10.1126/stke.2000.48.tw2

Adenomatous polyposis coli (APC) promotes the degradation of β-catenin. When APC is mutated, as in colon cancer cells, β-catenin accumulates in the nucleus, where it functions as a transcriptional coactivator of T-cell factor. The mechanism by which APC regulates β-catenin degradation has remained elusive. Now, Rosin-Arbesfeld et al. demonstrate that APC contains a functional nuclear export signal (NES), and that APC shuttles β-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 β-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 β-catenin to cotransactivate luciferase expression, whereas NES-mutated APC was unable to repress β-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]

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