Stabilized β-catenin extends thymocyte survival by up-regulating Bcl-xL

CD4(+)CD8(+) double-positive (DP) thymocytes, which are extremely sensitive to apoptosis, specifically up-regulate Bcl-x(L) to extend their lifespan. Deletion of the Bcl-x(L) gene leads to premature apoptosis of the thymocytes. In this study, we show that stabilization of beta-catenin, a critical coactivator for T cell factor (TCF), enhances DP thymocyte survival via up-regulating Bcl-x(L). Spontaneous or glucocorticoid-induced thymocyte apoptosis was associated with reduced levels of,beta-catenin and Bcl-x(L). Transgenic expression of a stabilized beta-catenin protected DP thymocytes from both spontaneous and glucocorticoid-induced apoptosis, resulting in significantly increased thymic cellularity. Compared with the wild-type mice, both protein and transcript levels of Bcl-x(L) were significantly increased in thymocytes of A-catenin transgenic mice. In addition, TCF-1 as well as beta-catenin were able to stimulate transcriptional activity of the reporter driven by a Bcl-x(L) promoter. beta-Catenin/TCF is thus able to act as a signal to up-regulate Bcl-x(L) levels in DP thymocytes, resulting in their enhanced survival.