Interaction between Smad7 and beta-catenin: importance for transforming growth factor beta-induced apoptosis
2005 (English)In: Molecular and Cellular Biology, ISSN 0270-7306, E-ISSN 1098-5549, Vol. 25, no 4, 1475-1488 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2005. Vol. 25, no 4, 1475-1488 p.
Animals, Apoptosis/drug effects/*physiology, COS Cells, Cell Fractionation, Cercopithecus aethiops, Cytoskeletal Proteins/*metabolism, DNA-Binding Proteins/*metabolism, Glycogen Synthase Kinase 3/metabolism, Humans, Male, Mice, Phosphorylation/drug effects, Prostatic Neoplasms/metabolism, Protein Binding/drug effects, Protein-Serine-Threonine Kinases/metabolism, Proto-Oncogene Proteins/metabolism, RNA; Small Interfering/metabolism, Research Support; Non-U.S. Gov't, Serine/metabolism, Trans-Activators/*metabolism, Transcription Factors/*metabolism, Transforming Growth Factor beta/*pharmacology, Tumor Cells; Cultured, p38 Mitogen-Activated Protein Kinases/metabolism
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-72728DOI: 10.1128/MCB.25.4.1475-1488.2005PubMedID: 15684397OAI: oai:DiVA.org:uu-72728DiVA: diva2:100639