Interaction between Smad7 and  -Catenin: Importance for Transforming Growth Factor  -Induced Apoptosis (original) (raw)

2005, Molecular and Cellular Biology

Members of the transforming growth factor ␤ (TGF-␤) and Wnt/wingless superfamilies regulate cell fate during development and tissue maintenance. Here we report that Smad7 interacts with ␤-catenin and lymphoid enhancer binding factor 1/T-cell-specific factor (LEF1/TCF), transcriptional regulators in Wnt signaling, in a TGF-␤-dependent manner. Smad7 was found to be required for TGF-␤1-induced accumulation of ␤-catenin and LEF1 in human prostate cancer (PC-3U) cells as well as in human keratinocytes (HaCaT cells). Moreover, when the endogenous Smad7 was repressed by specific small interfering RNA, TGF-␤-induced increase of activated p38, Akt phosphorylated on Ser473, glycogen synthase kinase 3␤ phosphorylated on Ser9 was prevented, as well as the TGF-␤-induced association between ␤-catenin and LEF1. Notably, the observed physical association of Smad7 and ␤-catenin was found to be important for TGF-␤-induced apoptosis, since suppression of ␤-catenin expression by small interfering RNA decreased the apoptotic response to TGF-␤.