Plakoglobin regulates the expression of the anti-apoptotic protein BCL-2

Plakoglobin is a cytoplasmic protein and a homologue of beta-catenin and Ar madillo of Drosophila with similar adhesive and signaling functions, These proteins interact with cadherins to mediate cell-cell adhesion and associat e with transcription factors to induce changes in the expression of genes i nvolved in cell fate determination and proliferation. Unlike the relatively well characterized role of beta-catenin in cell proliferation via activati on of c-MYC and cyclin D1 gene expression, the signaling function of plakog lobin in regulation of cell growth is undefined. Here, we show that high le vels of plakoglobin expression in plakoglobin-deficient human SCC9 cells le ads to uncontrolled growth and foci formation. Concurrent with the change i n growth characteristics we observe a pronounced inhibition of apoptosis, T his correlates with an induction of expression of BCL-2, a prototypic membe r of apoptosis-regulating proteins. The BCL-2 expression coincides with dec reased proteolytic processing and activation of caspase-3, an executor of p rogrammed cell death. Our data suggest that the growth regulatory function of plakoglobin is independent of its role in mediating cell-cell adhesion, These observations clearly implicate plakoglobin in pathways regulating cel l growth and provide initial evidence of its role as a pivotal molecular li nk between pathways regulating cell adherence and cell death.