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Interaction between Smad7 and ß-Catenin: Importance for Transforming Growth Factor ß-Induced Apoptosis

Sofia Edlund,¹ So Young Lee,^1, Susanne Grimsby,¹ Shouthing Zhang,¹ Pontus Aspenström,¹ Carl-Henrik Heldin,¹ and Maréne Landström^1*

Ludwig Institute for Cancer Research, Uppsala, Sweden¹

Received 9 July 2004/ Returned for modification 24 August 2004/ Accepted 29 October 2004

Members of the transforming growth factor ß (TGF-ß) and Wnt/wingless superfamilies regulate cell fate during development and tissue maintenance. Here we report that Smad7 interacts with ß-catenin and lymphoid enhancer binding factor 1/T-cell-specific factor (LEF1/TCF), transcriptional regulators in Wnt signaling, in a TGF-ß-dependent manner. Smad7 was found to be required for TGF-ß1-induced accumulation of ß-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-ß-induced increase of activated p38, Akt phosphorylated on Ser473, glycogen synthase kinase 3ß phosphorylated on Ser9 was prevented, as well as the TGF-ß-induced association between ß-catenin and LEF1. Notably, the observed physical association of Smad7 and ß-catenin was found to be important for TGF-ß-induced apoptosis, since suppression of ß-catenin expression by small interfering RNA decreased the apoptotic response to TGF-ß.

Supplemental material for this article may be found at http://mcb.asm.org.

Supplemental material for this article may be found at http://mcb.asm.org/.

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