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Interaction between Smad7 and beta-catenin : importance for transforming growth factor beta-induced apoptosis
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- Edlund, Sofia (author)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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- Lee, So Young (author)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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- Grimsby, Susanne (author)
- Uppsala universitet,Ludwiginstitutet för cancerforskning
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- (creator_code:org_t)
- 2005
- 2005
- English.
- In: Molecular and Cellular Biology. - 0270-7306 .- 1098-5549. ; 25:4, s. 1475-1488
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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.
Keyword
- 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
Publication and Content Type
- ref (subject category)
- art (subject category)
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