Interaction between Smad7 and beta-catenin: importance for transforming growth factor beta-induced apoptosis.

Members of the transforming growth factor beta (TGF-beta) and Wnt/wingless superfamilies regulate cell fate during development and tissue maintenance. Here we report that Smad7 interacts with beta-catenin and lymphoid enhancer binding factor 1/T-cell-specific factor (LEF1/TCF), transcriptional regulators in Wnt signaling, in a TGF-beta-dependent manner. Smad7 was found to be required ...
for TGF-beta1-induced accumulation of beta-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-beta-induced increase of activated p38, Akt phosphorylated on Ser473, glycogen synthase kinase 3beta phosphorylated on Ser9 was prevented, as well as the TGF-beta-induced association between beta-catenin and LEF1. Notably, the observed physical association of Smad7 and beta-catenin was found to be important for TGF-beta-induced apoptosis, since suppression of beta-catenin expression by small interfering RNA decreased the apoptotic response to TGF-beta.
Mesh Terms:
Animals, Apoptosis, COS Cells, Cell Fractionation, Cercopithecus aethiops, Cytoskeletal Proteins, DNA-Binding Proteins, Glycogen Synthase Kinase 3, Humans, Lymphoid Enhancer-Binding Factor 1, Male, Mice, Phosphorylation, Prostatic Neoplasms, Protein Binding, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, RNA, Small Interfering, Serine, Smad7 Protein, Trans-Activators, Transcription Factors, Transforming Growth Factor beta, Tumor Cells, Cultured, beta Catenin, p38 Mitogen-Activated Protein Kinases
Mol. Cell. Biol.
Date: Feb. 01, 2005
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