Open AccessInteraction between Smad7 and β-Catenin: Importance for Transforming Growth Factor β-Induced Apoptosis
Author(s) -
Sofia Edlund,
So Young Lee,
Susanne Grimsby,
Shouthing Zhang,
Pontus Aspenström,
CarlHenrik Heldin,
Maréne Landström
Publication year - 2005
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.25.4.1475-1488.2005
Subject(s) - biology , wnt signaling pathway , small interfering rna , gsk 3 , transforming growth factor , hacat , microbiology and biotechnology , beta catenin , catenin , cancer research , protein kinase b , phosphorylation , signal transduction , cell culture , transfection , genetics
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.