Nuclear Localization of Duplin, a β-Catenin-binding Protein, Is Essential for Its Inhibitory Activity on the Wnt Signaling Pathway

Kobayashi, Masashi; Kishida, Shosei; Fukui, Akimasa; Michiue, Tatsuo; Miyamoto, Yoichi; Okamoto, Tomoyoshi; Yoneda, Yoshihiro; Asashima, Makoto; Kikuchi, Akira

doi:10.1074/jbc.m108433200

Cited by 23 publications

(25 citation statements)

References 60 publications

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“…Contrary to our findings, previously published reports identified Chd8 as a negative regulator of canonical-Wnt/β-catenin signaling 10,13,36 . It is worth noting that these earlier studies were conducted in non-neuronal cells, suggesting that Chd8 could play cell-type specific roles in regulating Wnt signaling.…”

Section: Resultscontrasting

confidence: 99%

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Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling

et al. 2016

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De novo mutations in CHD8 are strongly associated with autism spectrum disorder (ASD), however the basic biology of CHD8 remains poor understood. Here we report that Chd8 knockdown during cortical development results in defective neural progenitor proliferation and differentiation that ultimately manifests in abnormal neuronal morphology and behaviors in adult mice. Transcriptome analysis revealed that while Chd8 stimulates the transcription of cell cycle genes, it also precludes the induction of neural specific genes by regulating the expression of PRC2 complex components. Furthermore, knockdown of Chd8 disrupts the expression of key transducers of Wnt signaling, and enhancing Wnt signaling rescues the transcriptional and behavioral deficits caused by Chd8 knockdown. We propose that these roles of Chd8 and the dynamics of Chd8 expression during development help negotiate the fine balance between neural progenitor proliferation and differentiation. Together, these observations provide new insights into the neurodevelopmental role of Chd8.Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

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Section: Resultscontrasting

confidence: 99%

“…It was initially identified as a binding partner and negative regulator of β-catenin signaling and was shown to be enriched in the promoters of transcriptionally active genes 10–13 . Homozygous deletion of Chd8 in mice results in early embryonic lethality resulting from massive apoptosis 13,14 .…”

Section: Introductionmentioning

confidence: 99%

Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling

et al. 2016

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“…Characterization of this fragment led to the conclusion that Duplin is a negative regulator of the Wnt signaling pathway and functions by blocking the binding of ␤-catenin to TCF (61). However, further studies also indicated that Duplin could attenuate the Wnt signaling pathway downstream of ␤-catenin target genes (38). Bioinformatic analysis suggests that Duplin arose from an improper splicing event, and no evidence for the existence of a human counterpart can be found (data not shown).…”

Section: Discussionmentioning

confidence: 99%

CHD8 Is an ATP-Dependent Chromatin Remodeling Factor That Regulates β-Catenin Target Genes

Thompson

Tremblay

Lin

et al. 2008

Molecular and Cellular Biology

179

163

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ATP-dependent chromatin remodeling by the CHD family of proteins plays an important role in the regulation of gene transcription. Here we report that full-length CHD8 interacts directly with ␤-catenin and that CHD8 is also recruited specifically to the promoter regions of several ␤-catenin-responsive genes. Our results indicate that CHD8 negatively regulates ␤-catenin-targeted gene expression, since short hairpin RNA against CHD8 results in the activation of several ␤-catenin target genes. This regulation is also conserved through evolution; RNA interference against kismet, the apparent Drosophila ortholog of CHD8, results in a similar activation of ␤-catenin target genes. We also report the first demonstration of chromatin remodeling activity for a member of the CHD6-9 family of proteins, suggesting that CHD8 functions in transcription through the ATP-dependent modulation of chromatin structure.The alteration of chromatin structure provides a key regulatory step for all processes that act upon DNA (41). The factors that regulate this structure, commonly referred to as chromatin remodeling enzymes, can be grouped into two broad categories: complexes that alter chromatin structure via the covalent modification of histones (25,42,83) and complexes that use the energy of ATP hydrolysis to alter the structure or position of the nucleosome (6,47,57,67).ATP-dependent chromatin remodeling enzymes modulate the contacts between histones and DNA. In vitro, these enzymes catalyze structural changes that allow factors to access nucleosomal DNA, reposition nucleosomes on a template, transfer histone octamers to donor DNA, and replace histones with histone variants (27,43,80). In vivo, these activities are crucial for transcription, replication, repair, and recombination of the eukaryotic genome (2,21,59,65). These remodeling enzymes can be divided into numerous families based on domain architecture. One such family is the CHD (chromodomain, helicase, DNA binding) group of proteins, which are critical regulators of chromatin structure (23,26,29,49). These enzymes are characterized by tandem chromodomains N-terminal to their catalytic Snf2 helicase domain.The CHD family can be further subdivided into three subfamilies: CHD1-2, CHD3-5, and CHD6-9. While the first two subfamilies have been extensively studied, very little is known about the CHD6-9 family (29, 49). Previous studies have indicated that CHD8 may regulate the Wnt signaling pathway, since an N-terminal fragment of CHD8 was previously identified as a protein in Rattus norvegicus that binds ␤-catenin both in vivo and in vitro (61). This N-terminal fragment, termed Duplin, contains only the chromodomains and lacks the Snf2 helicase domain and C-terminal sequences. Overexpression of this N-terminal fragment results in inhibition of Tcf4-dependent transcription, and studies of Xenopus embryos demonstrated that this fragment inhibited axis formation and ␤-catenin-mediated axis duplication (61).The "canonical" Wnt signaling pathway functions by controlling the soluble pool ...

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“…Since MITF is a candidate SUMO-target protein, the inhibitory effect of PIAS3 on MITF is presumably also linked to SUMO modification [47]. Another PIAS target in the Wnt pathway is duplin, a nuclear inhibitor of b-catenin [48]. Duplin has also been reported to bind to PIAS.…”

Section: Wnt Signallingmentioning

confidence: 97%

PIAS/SUMO: new partners in transcriptional regulation

Schmidt

Müller

2003

Cellular and Molecular Life Sciences (CMLS)

243

214

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Protein inhibitor of activated STATs (PIAS) proteins were initially identified as negative regulators of cytokine signalling that inhibit the activity of STAT-transcription factors. Evidence is accumulating that PIAS proteins function as transcriptional coregulators in various other important cellular pathways, including Wnt signalling, the p53 pathway and steroid hormone signalling. Most interestingly, recent work from several laboratories revealed that PIAS proteins act as E3-like ligases that stimulate the attachment of the ubiquitin-like SUMO modifier to target proteins acting in these pathways. Since in most cases the SUMO ligase activity and the transcriptional coregulator activity are functionally correlated, the PIAS/SUMO pathway appears to be an important mechanism of transcriptional regulation. In this review we will discuss some key findings that exemplify the role of PIAS proteins in the regulation of transcriptional processes and propose a model how the PIAS/ SUMO system may modulate transcriptional activities by mediating the assembly of coactivator or corepressor complexes within distinct subnuclear structures.

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Nuclear Localization of Duplin, a β-Catenin-binding Protein, Is Essential for Its Inhibitory Activity on the Wnt Signaling Pathway

Cited by 23 publications

References 60 publications

Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling

Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling

CHD8 Is an ATP-Dependent Chromatin Remodeling Factor That Regulates β-Catenin Target Genes

PIAS/SUMO: new partners in transcriptional regulation

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