Nuclear localization of the p120(ctn) Armadillo-like catenin is counteracted by a nuclear export signal and by E-cadherin expression

The Armadillo protein p120(ctn) associates with the cytoplasmic domain of c adherins and accumulates at cell-cell junctions. Particular Armadillo prote ins such as beta-catenin and plakophilins show a partly nuclear location, s uggesting gene-regulatory activities. For different human E-cadherin-negati ve carcinoma cancer cell lines we found expression of endogenous p120(ctn) in the nucleus. Expression of E-cadherin directed p120(ctn) out of the nucl eus. Previously, we reported that the human p120(ctn) gene might encode up to 32 protein isoforms as products of alternative splicing. Overexpression of p120(ctn) isoforms B in various cell lines resulted in cytoplasmic immun opositivity but never in nuclear staining. In contrast, upon-expression of p120(ctn) cDNAs lacking exon B, the isoforms were detectable within both nu clei and cytoplasm. A putative nuclear export signal (NES) with a character istic leucine-rich motif is encoded by exon B. This sequence element was sh own to be required for nuclear export and to function autonomously when fus ed to a carrier protein and microinjected into cell nuclei. Moreover, the N ES function of endogenously or exogenously expressed p120(ctn) isoforms B w as sensitive to the nuclear export inhibitor leptomycin B. Expression of ex ogenous E-cadherin down-regulated nuclear p120(ctn) whereas activation of p rotein kinase C increased the level of nuclear p120(ctn). These results rev eal molecular mechanisms controlling the subcellular distribution of p120(c tn).