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

Edlund, Sofia; Lee, So Young; Grimsby, Susanne; Zhang, Shouthing; Aspenström, Pontus; Heldin, Carl‐Henrik; Landström, Maréne

doi:10.1128/mcb.25.4.1475-1488.2005

Cited by 123 publications

(119 citation statements)

References 62 publications

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“…A cross-talk between TGF-β and Wnt signaling pathways through physical association of β-catenin and Smad7 has been reported (Edlund et al, 2005). This cross-talk was found to be important for TGF-β-induced apoptosis.…”

Section: Discussionmentioning

confidence: 93%

Lithium inhibits Smad3/4 transactivation via increased CREB activity induced by enhanced PKA and AKT signaling

Liang¹,

Wendland²,

Chuang³

2008

Molecular and Cellular Neuroscience

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Smad proteins are intracellular transducers for transforming growth factor-β (TGF-β signaling and play a critical role in differentiation, tissue repair and apoptosis of the central nervous system. Both TGF-β and its regulated gene, plasminogen activator inhibitor type-1 (PAI-1), have been implicated in the etiology and progression of neurodegenerative diseases and mood disorders. We previously reported that GSK-3β protein depletion suppresses Smad3/4-dependent gene transcription and causes a reduction in PAI-1 expression. Here, we provide evidence that lithium, the drug for the treatment and prophylaxis of bipolar disorder, inhibits Smad-dependent signaling by regulating cAMP-protein kinase A (PKA), AKT-glycogen synthase kinase-3β (GSK-3β), and CRE-dependent signaling pathways in neuron-enriched cerebral cortical cultures of rats. We demonstrate that lithium-induced activation of these pathways inhibits Smad3/4-dependent gene transcription through an increase in pCREB Ser133 protein levels, an enhanced interaction between pCREB Ser133 and p300/CBP, which causes Smad3/4-p300/CBP complex disruption and transcriptional suppression of Smad3/4-dependent genes. Therapeutic implications of our findings are discussed.

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Section: Discussionmentioning

confidence: 93%

Lithium inhibits Smad3/4 transactivation via increased CREB activity induced by enhanced PKA and AKT signaling

Liang¹,

Wendland²,

Chuang³

2008

Molecular and Cellular Neuroscience

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“…However, a proapoptotic role of HGF (Arakaki et al, 1998;Matteucci et al, 2003;Rasola et al, 2004) and b-catenin (Kim et al, 2000;van Gijn et al, 2001;Edlund et al, 2005) was also reported in several models. Here, we show that the HGFR transduction axis and the b-catenin/TCF pathway cooperate in underpinning survival signals, whose importance probably increases during carcinoma progression.…”

Section: Discussionmentioning

confidence: 99%

A positive feedback loop between hepatocyte growth factor receptor and β-catenin sustains colorectal cancer cell invasive growth

et al. 2006

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Overexpressed or activated hepatocyte growth factor receptor, encoded by the MET proto-oncogene, was found in the majority of colorectal carcinomas (CRCs), whose stepwise progression to malignancy requires transcriptional activation of b-catenin. We here demonstrate that a functional crosstalk between Met and b-catenin signaling sustains and increases CRC cell invasive properties. Hepatocyte growth factor (HGF) stimulation prompts b-catenin tyrosine phosphorylation and dissociation from Met, and upregulates b-catenin expression via the phosphatidylinositol 3-kinase pathway in conditions that mimic those found by the invading and metastasizing cells. Additionally, a transcriptionally active form of b-catenin, known to be oncogenic, enhances Met expression. Furthermore, HGF treatment increases the activity of the b-catenin-regulated T-cell factor transcription factor in cells expressing the wild-type or the oncogenic b-catenin. In the mirror experiments, either Met or b-catenin knocking down also reduces their protein level. In biological assays, b-catenin knocking down abrogates the HGF-induced motile phenotype, whereas active b-catenin fosters ligand-independent cell scattering. Met and b-catenin also cooperate in promoting entry into the cell cycle and in protecting cells from apoptosis. In conclusion, Met and b-catenin pathways are mutually activated in CRC cells. This might generate a selfamplifying positive feedback loop resulting in the upregulation of the invasive growth properties of CRC cells.

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“…In turn, these complexes inhibit phosphorylation of ␤-catenin and thereby its degradation (62). Furthermore, SMAD 7 interacts with ␤-catenin to modulate TGF-␤ induced apoptosis, as SMAD7 acts as positive regulator of the TGF-␤-activated pathway involving TAK1-MKK3 and p38 mitogen-activated kinases, leading to induction of c-Myc and p53 and subsequently apoptosis (46,(62)(63)(64). Indeed, increased apoptosis was detected by PARP1 cleavage, despite of the proliferative phenotype.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of Biglycan Causes Cardiac Fibroblasts to Differentiate into a Myofibroblast Phenotype

Melchior-Becker

Dai

Ding

et al. 2011

Journal of Biological Chemistry

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Myocardial infarction (MI) is followed by extracellular matrix (ECM) remodeling, which is on the one hand required for the healing response and the formation of stable scar tissue. However, on the other hand, ECM remodeling can lead to fibrosis and decreased ventricular compliance. The small leucine-rich proteoglycan (SLRP), biglycan (bgn), has been shown to be critically involved in these processes. During post-infarct remodeling cardiac fibroblasts differentiate into myofibroblasts which are the main cell type mediating ECM remodeling. The aim of the present study was to characterize the role of bgn in modulating the phenotype of cardiac fibroblasts. Cardiac fibroblasts were isolated from hearts of wild-type (WT) versus bgn ؊/0 mice. Phenotypic characterization of the bgn

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

Cited by 123 publications

References 62 publications

Lithium inhibits Smad3/4 transactivation via increased CREB activity induced by enhanced PKA and AKT signaling

Lithium inhibits Smad3/4 transactivation via increased CREB activity induced by enhanced PKA and AKT signaling

A positive feedback loop between hepatocyte growth factor receptor and β-catenin sustains colorectal cancer cell invasive growth

Deficiency of Biglycan Causes Cardiac Fibroblasts to Differentiate into a Myofibroblast Phenotype

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