Plakoglobin (γ-catenin) has TCF/LEF family-dependent transcriptional activity in β-catenin-deficient cell line

Maeda, Osamu; Usami, Noriyasu; Kondo, Masashi; Takahashi, Masahide; Goto, Hidemi; Shimokata, Kaoru; Kusugami, Kazuo; Sekido, Yoshitaka

doi:10.1038/sj.onc.1207254

Cited by 143 publications

(140 citation statements)

References 31 publications

(33 reference statements)

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“…g-catenin) to promote survivin transcription. g-Catenin is a closely related homolog of b-catenin, which has been previously reported to have TCFdependent transcriptional activity in b-catenin-deficient cells (Maeda et al, 2004). We detected upregulation of g-catenin in the nucleus of Hb92 cells, whereas no g-catenin was detected in the nucleus in the parental HCT116 and Hb18 cells ( Figure 2d).…”

Section: Icg-001 Inhibits Survivin Gene Transcription and Expression mentioning

confidence: 64%

Differential roles for the coactivators CBP and p300 on TCF/β-catenin-mediated survivin gene expression

et al. 2005

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The inhibitor of apoptosis (IAP) protein survivin is highly expressed in cancers, but not in normal differentiated tissues. TCF/b-catenin signaling has been reported to participate in the regulation of survivin transcription in colon cancer. We have recently characterized ICG-001, a small molecule specific inhibitor of the b-catenin/ Creb-binding protein (CBP) interaction. Inhibition of the b-catenin/CBP interaction represses a subset of TCF/bcatenin-mediated transcription. ICG-001 potently inhibits survivin gene transcription and expression. ICG-001-mediated downregulation of survivin expression enhanced caspase-3 activity and apoptosis, which was rescued by overexpression of wild type but not mutant (C84A) survivin. Small interfering RNA and genetic reduction of CBP also decreased survivin expression. Chromatin immunoprecipitation assay confirmed that CBP is the crucial coactivator for TCF/b-catenin-mediated survivin transcription. Furthermore, ICG-001-induced recruitment of p300 to the survivin promoter led to concomitant recruitment of SUMO-1, HDAC6 and PML proteins, which have been associated with transcriptional repression. These findings demonstrate that CBP and p300 play very distinct roles in survivin gene transcription.

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Section: Icg-001 Inhibits Survivin Gene Transcription and Expression mentioning

confidence: 64%

Differential roles for the coactivators CBP and p300 on TCF/β-catenin-mediated survivin gene expression

et al. 2005

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“…25 Although plakoglobin and b-catenin are closely related factors, differences in their downstream signaling pathways have recently been suggested in studies using a malignant mesothelioma cell line deficient in b-catenin (NCI-H28), where cyclin D1 has specifically been shown to be a target gene for b-catenin but not for plakoglobin. 26 In human breast biopsies taken from normal breast epithelium, Fibro adenoma of the breast and breast carcinoma, levels of Brn3b mRNA and protein also inversely correlated with plakoglobin mRNA and protein levels. Therefore, it appears that as the disease progresses, Brn-3b is over-expressed, whereas plakoglobin expression is either low or lost.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, plakoglobin was shown to have TCF/LEF family-dependent transcriptional activity in a b-catenin deficient cell line which indicates its crucial role as a transcription factor and regulator of gene expression. 26 b-Catenin and plakoglobin are vertebrate homologs of Drosophila armadillo, functioning in cell adhesion, the Wnt signaling pathway and transactivation. 26,28 Their activities are controlled by 3 types of interactions: those with cadherins in cell-cell junctions, linking them to the cytoskeleton; interactions in the nucleus, where they bind to transcription factors such as TCF/LEF and stimulate gene expression; and interactions of free cytoplasmic b-catenin with axin and adenomatous polyposis coli (APC) protein, which target it for degradation in the absence of Wnt signals.…”

Section: Discussionmentioning

confidence: 99%

“…26 b-Catenin and plakoglobin are vertebrate homologs of Drosophila armadillo, functioning in cell adhesion, the Wnt signaling pathway and transactivation. 26,28 Their activities are controlled by 3 types of interactions: those with cadherins in cell-cell junctions, linking them to the cytoskeleton; interactions in the nucleus, where they bind to transcription factors such as TCF/LEF and stimulate gene expression; and interactions of free cytoplasmic b-catenin with axin and adenomatous polyposis coli (APC) protein, which target it for degradation in the absence of Wnt signals. 29 Secreted proteins of the Wnt family play roles in the regulation of embryonic development and aberrant activation of the Wnt/bcatenin pathway is one of the most frequent abnormality known in human cancer.…”

Section: Discussionmentioning

confidence: 99%

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The Brn‐3b POU family transcription factor represses plakoglobin gene expression in human breast cancer cells

Samady

Faulkes

Budhram-Mahadeo

et al. 2005

Intl Journal of Cancer

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The Brn-3b transcription factor has been shown to be overexpressed in human breast cancer cells and contributes toward cell growth regulation. Using micro-arrays, more than 50 cancerrelated genes regulated by Brn-3b in human breast cancer cells have been identified. For example, Brn-3b activates the cell cycle regulator CDK4 that provides a mechanism by which Brn-3b controls the growth of breast cancer cells. Here, we show that Brn-3b regulates plakoglobin (c-catenin), a member of the catenin family involved in cell-cell adhesion and signal transduction. Brn-3b expression inversely correlates with plakoglobin expression at both mRNA and protein levels in breast cancer cell lines and human breast biopsies. In contrast, no significant correlation was observed between Brn-3b expression and b-catenin, or between Brn-3b expression and E-cadherin expression. Brn-3b represses the plakoglobin promoter via a Brn-3 consensus binding site contained within the region 2965 to 2593 relative to the transcriptional start site. Both repression of the promoter and binding of Brn-3b are lost when this site is mutated. To our knowledge, this is the first time that a Brn-3b POU family transcription factor has been shown to regulate a member of the catenin family, which provides insight into the molecular mechanisms by which Brn-3b expression may favour breast cancer progression and tumor invasion. ' 2005 Wiley-Liss, Inc.Key words: breast cancer; metastasis; Brn-3b transcription factor; Plakoglobin (g-catenin), micro-arrayThe POU (Pit-Oct-Unc) family of transcription factors were originally identified on the basis of a common DNA binding domain, referred to as the POU domain, present in the mammalian transcription factors Pit-1, Oct-1 and Oct-2 and the nematode regulatory protein Unc-86. 1,2 A number of POU family transcription factors have been identified in the nervous system where they have been shown to play a critical role in the regulation of gene expression. Thus, the closely related POU family transcription factors Brn-3a, Brn-3b and Brn-3c were originally identified on the basis of their distinct but overlapping patterns of gene expression in the developing and adult nervous systems. [3][4][5][6] Inactivation of the individual genes encoding these factors has been shown to produce defects in the development of specific parts of the nervous system. 7-9 However, expression of Brn-3a and Brn-3b has also been observed in non-neuronal cells such as in the testis, 10 breast 11 and cervix. 4,12 Changes in expression of Brn-3a and Brn-3b have been reported in tumors derived from the cells which normally express them, suggesting a role for this family of transcription factors in cancer. Indeed, Brn-3a has been shown to be overexpressed in aggressive neuroendocrine tumors, 13 whilst Brn-3b is expressed at high levels in human neuroblastomas. 14,15 Similarly, Brn-3a is highly overexpressed in human cervical intraepithelial neoplasia grade 3 (CIN3), compared to normal human cervical samples. 12 Interestingly, our previous studies have ...

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“…However, an emerging view is that desmosomes, like the classical adherens junctions, are involved in signaling pathways that dictate or maintain the differentiation status or program of the cells [1]. Due to its functional similarity to β-catenin in desmosomes, the armadillo protein PKG, also called γ-catenin, has been at the center of investigation with ample evidence to support a signaling role besides its adhesive role [37,38]. These two possibilities of desmosome function are by no means mutually exclusive and more in vivo experiments will be required to thoroughly explore the signaling role desmosomal components.…”

Section: Models and Cancermentioning

confidence: 99%

Broken hearts, woolly hair, and tattered skin: when desmosomal adhesion goes awry

Bazzi

Christiano

2007

Current Opinion in Cell Biology

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Desmosomal cadherins constitute the adhesive core of desmosomes. The different types of these cadherins are differentially expressed in a tissue specific as well as differentiation dependent manner. The skin and the heart are two examples of tissues whose vital functions require the ability to endure mechanical stress, and therefore, the integrity of desmosomal adhesion. When this adhesion is compromised via mutations in genes encoding desmosomal cadherins or associated plaque proteins, both tissues can suffer the consequences. Open questions revolve around whether the resulting phenotypes are solely due to physical disruption of cell adhesion, or whether these events are coupled with signaling mechanisms that influence many additional cellular processes. In this review, we focus on new developments in desmosomal adhesion with an emphasis on the skin, hair and heart.

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Plakoglobin (γ-catenin) has TCF/LEF family-dependent transcriptional activity in β-catenin-deficient cell line

Cited by 143 publications

References 31 publications

Differential roles for the coactivators CBP and p300 on TCF/β-catenin-mediated survivin gene expression

Differential roles for the coactivators CBP and p300 on TCF/β-catenin-mediated survivin gene expression

The Brn‐3b POU family transcription factor represses plakoglobin gene expression in human breast cancer cells

Broken hearts, woolly hair, and tattered skin: when desmosomal adhesion goes awry

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