Frodo Links Dishevelled to the p120-Catenin/Kaiso Pathway: Distinct Catenin Subfamilies Promote Wnt Signals

Park, Jae-Il; Ji, Hong; Jun, Suckjoon; Gu, Dongmin; Hikasa, Hiroki; Li, Lei; Sokol, Sergei Y.; McCrea, Pierre D.

doi:10.1016/j.devcel.2006.09.022

Cited by 91 publications

(106 citation statements)

References 59 publications

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“…Other potential means of modulating the nuclear entry of ␦-catenin exist. As we and others have indicated, signaling pools of p120-catenin subfamily members, including ␦-catenin, appear to be subject to canonical Wnt signals or the pathway's destruction complex (63)(64)(65)(66). For p120 itself (and ␦-catenin?…”

Section: Apoptosis or Programmed Cell Death Is A Physiologicallymentioning

confidence: 98%

Caspase-3 Cleavage Links δ-Catenin to the Novel Nuclear Protein ZIFCAT

Tonthat

Lee

et al. 2011

Journal of Biological Chemistry

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␦-Catenin is an Armadillo protein of the p120-catenin subfamily capable of modulating cadherin stability, small GTPase activity, and nuclear transcription. From yeast twohybrid screening of a human embryonic stem cell cDNA library, we identified ␦-catenin as a potential interacting partner of the caspase-3 protease, which plays essential roles in apoptotic as well as non-apoptotic processes. Interaction of ␦-catenin with caspase-3 was confirmed using cleavage assays conducted in vitro, in Xenopus apoptotic extracts, and in cell line chemically induced contexts. The cleavage site, a highly conserved caspase consensus motif (DELD) within Armadillo repeat 6 of ␦-catenin, was identified through peptide sequencing. Cleavage thus generates an amino-terminal (residues 1-816) and carboxyl-terminal (residues 817-1314) fragment, each containing about half of the central Armadillo domain. We found that cleavage of ␦-catenin both abolishes its association with cadherins and impairs its ability to modulate small GTPases. Interestingly, 817-1314 possesses a conserved putative nuclear localization signal that may facilitate the nuclear targeting of ␦-catenin in defined contexts. To probe for novel nuclear roles of ␦-catenin, we performed yeast two-hybrid screening of a mouse brain cDNA library, resolving and then validating interaction with an uncharacterized KRAB family zinc finger protein, ZIFCAT. Our results indicate that ZIFCAT is nuclear and suggest that it may associate with DNA as a transcriptional repressor. We further determined that other p120 subfamily catenins are similarly cleaved by caspase-3 and likewise bind ZIFCAT. Our findings potentially reveal a simple yet novel signaling pathway based upon caspase-3 cleavage of p120-catenin subfamily members, facilitating the coordinate modulation of cadherins, small GTPases, and nuclear functions.

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Section: Apoptosis or Programmed Cell Death Is A Physiologicallymentioning

confidence: 98%

Caspase-3 Cleavage Links δ-Catenin to the Novel Nuclear Protein ZIFCAT

Tonthat

Lee

et al. 2011

Journal of Biological Chemistry

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“…An absence of p120 also has been reported to disrupt CK1 -mediated phosphorylation of Dvl2 [305]. In turn, signaling through the proteins Dishevelled and Frodo regulates the stability of p120 [309].…”

Section: Connections Between the Wnt-frizzled-lrp5/6 Signalosome And mentioning

confidence: 99%

Wnt/beta-Catenin Signaling and Small Molecule Inhibitors

Voronkov¹,

Krauß²

2012

CPD

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Wnt/ -catenin signaling is a branch of a functional network that dates back to the first metazoans and it is involved in a broad range of biological systems including stem cells, embryonic development and adult organs. Deregulation of components involved in Wnt/ -catenin signaling has been implicated in a wide spectrum of diseases including a number of cancers and degenerative diseases. The key mediator of Wnt signaling, -catenin, serves several cellular functions. It functions in a dynamic mode at multiple cellular locations, including the plasma membrane, where -catenin contributes to the stabilization of intercellular adhesive complexes, the cytoplasm where -catenin levels are regulated and the nucleus where -catenin is involved in transcriptional regulation and chromatin interactions. Central effectors of -catenin levels are a family of cysteine-rich secreted glycoproteins, known as Wnt morphogens. Through the LRP5/6-Frizzled receptor complex, Wnts regulate the location and activity of the destruction complex and consequently intracellularcatenin levels. However, -catenin levels and their effects on transcriptional programs are also influenced by multiple other factors including hypoxia, inflammation, hepatocyte growth factor-mediated signaling, and the cell adhesion molecule E-cadherin. The broad implications of Wnt/ -catenin signaling in development, in the adult body and in disease render the pathway a prime target for pharmacological research and development. The intricate regulation of -catenin at its various locations provides alternative points for therapeutic interventions.

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“…By inhibiting Kaiso activity, nuclear p120catenin activates the transcription of a number of potent tumour suppressors, including E-cadherin [42], Xist [138], Rb [139] and mts-1 [140] and could therefore act as a tumour suppressor (figure 3a). On the other hand, the interaction between p120catenin and Kaiso induces the canonical Wnt signalling pathway [141,142], which has been shown to promote tumour cell infiltration and metastasis [143,144], notably through the upregulation of the matrixdegrading enzyme and metastasis-promoting gene MMP-7 (matrysilin; figure 3b) [145]. Interestingly, functional regulator of dishevelled in ontogenesis (Frodo), a downstream target of Wnt/Dsh signalling, associates with p120catenin and reinforces p120catenin-mediated inhibition of Kaiso and thus further increases the expression of Wnt/b-catenin target genes [142].…”

Section: (B) P120catenin Interacts With Kaiso To Control Gene Transcrmentioning

confidence: 99%

“…On the other hand, the interaction between p120catenin and Kaiso induces the canonical Wnt signalling pathway [141,142], which has been shown to promote tumour cell infiltration and metastasis [143,144], notably through the upregulation of the matrixdegrading enzyme and metastasis-promoting gene MMP-7 (matrysilin; figure 3b) [145]. Interestingly, functional regulator of dishevelled in ontogenesis (Frodo), a downstream target of Wnt/Dsh signalling, associates with p120catenin and reinforces p120catenin-mediated inhibition of Kaiso and thus further increases the expression of Wnt/b-catenin target genes [142]. Another positive feedback loop involves the phosphorylation of p120catenin by CK11 in response to Wnt3a signalling.…”

Section: (B) P120catenin Interacts With Kaiso To Control Gene Transcrmentioning

confidence: 99%

p120catenin alteration in cancer and its role in tumour invasion

Péglion

Etienne-Manneville

2013

Phil. Trans. R. Soc. B

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Since its discovery in 1989 as a substrate of the Src oncogene, p120catenin has been revealed as an important player in cancer initiation and tumour dissemination. p120catenin regulates a wide range of cellular processes such as cell–cell adhesion, cell polarity and cell proliferation and plays a pivotal role in morphogenesis, inflammation and innate immunity. The pleiotropic effects of p120catenin rely on its interactions with numerous partners such as classical cadherins at the plasma membrane, Rho-GTPases and microtubules in the cytosol and transcriptional modulators in the nucleus. Alterations of p120catenin in cancer not only concern its expression level but also its intracellular localization and can lead to both pro-invasive and anti-invasive effects. This review focuses on the p120catenin-mediated pathways involved in cell migration and invasion and discusses the potential consequences of major cancer-related p120catenin alterations with respect to tumour spread.

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Frodo Links Dishevelled to the p120-Catenin/Kaiso Pathway: Distinct Catenin Subfamilies Promote Wnt Signals

Cited by 91 publications

References 59 publications

Caspase-3 Cleavage Links δ-Catenin to the Novel Nuclear Protein ZIFCAT

Caspase-3 Cleavage Links δ-Catenin to the Novel Nuclear Protein ZIFCAT

Wnt/beta-Catenin Signaling and Small Molecule Inhibitors

p120catenin alteration in cancer and its role in tumour invasion

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