A Novel β-Catenin-binding Protein Inhibits β-Catenin-dependent Tcf Activation and Axis Formation

Sakamoto, Ikuo; Kishida, Shosei; Fukui, Akimasa; Kishida, Michiko; Yamamoto, Hideki; Hino, Shinjiro; Michiue, Tatsuo; Takada, Shinji; Asashima, Makoto; Kikuchi, Akira

doi:10.1074/jbc.m004089200

Cited by 96 publications

(117 citation statements)

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“…2B). These results are consistent with the previous observations that Duplin-(482-749) was present in the nucleus and that Duplin-(1-482) was localized in the cytoplasm (40 (40). One or two clusters of basic amino acids are classical NLSs recognized by importin ␣ (52).…”

Section: Identification Of Importin ␣ As a Duplin-binding Protein-supporting

confidence: 83%

“…The structures of all plasmids were confirmed by restriction enzyme analysis and, in most cases, by DNA sequence analysis across crucial regions. pCGN/Duplin, pBJ-Myc/ Duplin, pEF-BOS-HA/hTcf-4E, pSP-Myc/Duplin, pGEX-GFP, and pGEX/SV40NLS-GFP were constructed as described (19,40,46).…”

Section: Methodsmentioning

confidence: 99%

“…MBP-importin ␣-P was precipitated by centrifugation, then the precipitates were probed with the anti-GST antibody. To determine whether various Duplin mutants interact with ␤-catenin in intact cells, the assays were carried out as described (40).…”

Section: Methodsmentioning

confidence: 99%

“…Effect of Nuclear Localization of Duplin on Its Function-In a prior study (40), we demonstrated that Duplin binds to ␤-catenin and inhibits the binding of ␤-catenin to Tcf, thereby repressing ␤-catenin-dependent Tcf transcriptional activation. We examined whether nuclear localization is necessary for these functions of Duplin.…”

Section: Identification Of Importin ␣ As a Duplin-binding Protein-mentioning

confidence: 99%

“…We have recently identified a novel protein that binds to ␤-catenin in the nucleus and designated it Duplin (40). Duplin inhibits the binding of ␤-catenin to Tcf-4, thereby inhibiting Wnt-3a-and ␤-catenin-dependent Tcf-4 activation in mammalian cells.…”

mentioning

confidence: 99%

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

Kobayashi

Kishida

Fukui

et al. 2002

Journal of Biological Chemistry

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Duplin binds to ␤-catenin and inhibits the Wnt signaling pathway, thereby leading to repression of the ␤-catenin-mediated transactivation and Xenopus axis formation. To find an additional function of Duplin, yeast two-hybrid screening was carried out. Importin ␣ was isolated as a binding protein of Duplin. Importin ␣ bound directly to basic amino acid clusters of Duplin. Although Duplin was present in the nucleus, deletion of the basic amino acid clusters (Duplin ⌬500 -584 ) retained Duplin in the cytoplasm. Duplin ⌬500 -584 bound to ␤-catenin as efficiently as wild-type Duplin, but it neither repressed Wntdependent Tcf transcriptional activation in mammalian cells nor showed ventralization in Xenopus embryos. The Duplin mutant without a ␤-catenin-binding region lost the ability to inhibit the Wnt-dependent Tcf activation, but retained its ventralizing activity. Furthermore, Duplin not only suppressed ␤-catenin-dependent axis duplication and expression of siamois, a Wnt-regulated gene, but also inhibited siamois-dependent axis duplication. These results indicate that Duplin is translocated to the nucleus by interacting with importin ␣, and that nuclear localization is essential for the function of Duplin. Moreover, Duplin has an additional activity of inhibiting the Wnt signaling pathway by affecting the downstream ␤-catenin target genes.

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Section: Identification Of Importin ␣ As a Duplin-binding Protein-supporting

confidence: 83%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Identification Of Importin ␣ As a Duplin-binding Protein-mentioning

confidence: 99%

mentioning

confidence: 99%

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

Kobayashi

Kishida

Fukui

et al. 2002

Journal of Biological Chemistry

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Rise of the Chromodomain Helicase DNA‐Binding (CHD) Chromatin Remodelling Machines

Alendar

2023

Encyclopedia of Life Sciences

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Vital processes such as transcription, repair, replication and recombination continuously shape cellular chromatin landscape. The chromodomain helicase DNA‐binding (CHD) family of enzymes regulate chromatin dynamics by utilising energy from ATP hydrolysis to alter nucleosomal position, structure and composition, thereby modulating accessibility of the underlying DNA sequence. The CHD enzymes are highly conserved in evolution, and genetic studies in fungi, plants and animals demonstrate their critical roles in regulation of cellular identity and fate and organismal development. Advances in genomic studies over the past two decades led to the identification of frequent DNA copy‐number alterations, mutations and aberrant expression of CHDs in human malignancies and various disorders, highlighting their importance as relevant biomarkers or targets for therapeutic intervention. Key Concepts CHD family of enzymes (CHD1‐9) are evolutionary conserved ATP‐dependent chromatin remodelers that mobilise nucleosomes to regulate DNA‐templated processes, such as transcription, replication and repair. They are critical for normal organismal development and are frequently mutated in human disorders and cancers. Chromodomain helicase DNA‐binding proteins (CHD1‐9) are evolutionary conserved family of ATP‐dependent chromatin remodelers that mobilise nucleosomes to regulate DNA‐templated processes such as transcription, replication and DNA repair. CHD enzymes share a common domain structure: two N‐terminal chromodomains, a central ATPase/helicase domain, and a C‐terminal DNA‐binding domain. CHD proteins play crucial roles in diverse cellular processes, including embryonic development, stem cell maintenance and differentiation, and tissue‐specific gene expression. Dysregulation of CHD proteins has been associated with various human diseases, including cancer and neurodevelopmental disorders. CHD proteins are attractive targets for the development of new therapies for diseases associated with chromatin dysfunction. Understanding the molecular mechanisms underlying the function of CHD proteins may pave the way for the development of new drugs that target these proteins and improve the treatment of a variety of human diseases.

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An Overview of Gene Regulation by Wnt/β‐Catenin Signaling

Zhang¹,

Cadigan²

2014

WNT Signaling in Development and Disease

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A Novel β-Catenin-binding Protein Inhibits β-Catenin-dependent Tcf Activation and Axis Formation

Cited by 96 publications

References 57 publications

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

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

Rise of the Chromodomain Helicase DNA‐Binding (CHD) Chromatin Remodelling Machines

An Overview of Gene Regulation by Wnt/β‐Catenin Signaling

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