Zipper-interacting Protein Kinase (ZIPK) Modulates Canonical Wnt/β-Catenin Signaling through Interaction with Nemo-like Kinase and T-cell Factor 4 (NLK/TCF4)

Togi, Sumihito; Ikeda, Osamu; Kamitani, Shinya; Togi, Misa; Sekine, Yoshifumi; Muromoto, Ryuta; Nanbo, Asuka; Oritani, Kenji; Kawai, Taro; Akira, Shizuo; Matsuda, Tadashi

doi:10.1074/jbc.m110.189829

Cited by 28 publications

(25 citation statements)

References 33 publications

(36 reference statements)

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“…Ectopic expression or knockdown of ZIPK disrupts or enhances NLK-TCF4 complex formation respectively. These results indicate that ZIPK serves as a positive regulator of Wnt/β-catenin signalling via interaction with NLK [149]. In addition, we recently reported that DP1, which binds to E2F and enhances E2F activity for regulation of the cell cycle, plays a positive role in Wnt/βcatenin signalling by binding to NLK and suppressing its kinase activity [30,31].…”

Section: Novel Regulators Acting On the β-Catenin-tcf Complexmentioning

confidence: 76%

Wnt/β-catenin signalling: from plasma membrane to nucleus

Kim

Jho

2013

Biochemical Journal

272

211

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Wnt/β-catenin signalling plays essential roles in embryonic development as well as tissue homoeostasis in adults. Thus abnormal regulation of Wnt/β-catenin signalling is linked to a variety of human diseases, including cancer, osteoporosis and Alzheimer's disease. Owing to the importance of Wnt signalling in a wide range of biological fields, a better understanding of its precise mechanisms could provide fundamental insights for therapeutic applications. Although many studies have investigated the regulation of Wnt/β-catenin signalling, our knowledge remains insufficient due to the complexity and diversity of Wnt signalling. It is generally accepted that the identification of novel regulators and their functions is a prerequisite to fully elucidating the regulation of Wnt/β-catenin signalling. Recently, several novel modulators of Wnt signalling have been determined through multiple genetic and proteomic approaches. In the present review, we discuss the mechanistic regulation of Wnt/β-catenin signalling by focusing on the roles of these novel regulators.

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Section: Novel Regulators Acting On the β-Catenin-tcf Complexmentioning

confidence: 76%

Wnt/β-catenin signalling: from plasma membrane to nucleus

Kim

Jho

2013

Biochemical Journal

272

211

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“…Therefore, a loss or reduction of PIAS4 could affect downstream regulation of this pathway. The DAPK3 gene is a serine/threonine kinase is involved in apoptosis and transcriptional regulation including canonical Wnt /β‐catenin signaling [Togi et al, ]. The NMRK2 gene, also known as ( MIBP ), is a muscle integrin binding protein expressed in skeletal and cardiac muscle.…”

Section: Discussionmentioning

confidence: 99%

Clinical Comparison of Overlapping Deletions of 19p13.3

Risheg¹,

Pasion

Sacharow

et al. 2013

American J of Med Genetics Pt A

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We present three patients with overlapping interstitial deletions of 19p13.3 identified by high resolution SNP microarray analysis. All three had a similar phenotype characterized by intellectual disability or developmental delay, structural heart abnormalities, large head relative to height and weight or macrocephaly, and minor facial anomalies. Deletion sizes ranged from 792 Kb to 1.0 Mb and included a common region arr [hg19] 19p13.3 (3,814,392-4,136,989), containing eight genes: ZFR2, ATCAY, NMRK2, DAPK3, EEF2, PIAS4, ZBTB7A, MAP2K2, and two non-coding RNA's MIR637 and SNORDU37. The patient phenotypes were compared with three previous single patient reports with similar interstitial 19p13.3 deletions and six additional patients from the DECIPHER and ISCA databases to determine if a common haploinsufficient phenotype for the region can be established.

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“…Additionally, human DAPK3 regulates a variety of signaling pathways commonly deregulated in cancer. For example, DAPK3 negatively regulates the canonical Wnt/ β-catenin pathway by disrupting the interaction between Nemo-like kinase and T-cell Factor 4 in colon cancer cell lines(7). It also regulates androgen receptor-mediated transcription via ubiquitination and degradation of androgen receptor in various cancer cell lines (8).…”

Section: Introductionmentioning

confidence: 99%

DAPK3 Suppresses Acini Morphogenesis and Is Required for Mouse Development

Kocher

White

Piwnica‐Worms

2015

Molecular Cancer Research

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Death-associated protein kinase (DAPK3) is a serine/threonine kinase involved in various signaling pathways important to tissue homeostasis and mammalian biology. Considered to be a putative tumor suppressor, the molecular mechanism by which DAPK3 exerts its suppressive function is not fully understood and the field lacks an appropriate mouse model. To address these gaps, an in vitro 3D tumorigenesis model was used and a constitutive DAPK3 knockout mouse was generated. In the 3D morphogenesis model, loss of DAPK3 through lentiviral-mediated knockdown enlarged acinar size by accelerated acini proliferation and apoptosis while maintaining acini polarity. Depletion of DAPK3 enhanced growth factor-dependent mTOR activation and, furthermore, enlarged DAPK3 acini structures were uniquely sensitive to low doses of rapamycin. Simultaneous knockdown of RAPTOR, a key mTORC1 component, reversed the augmented acinar size in DAPK3-depleted structures indicating an epistatic interaction. Utilizing a validated gene trap strategy to generate a constitutive DAPK3 knockout mouse, it was demonstrated that DAPK3 is vital for early mouse development. The Dapk3 promoter exhibits spatio-temporal activity in developing mice and is actively expressed in normal breast epithelia of adult mice. Importantly, reduction of DAPK3 expression correlates with the development of DCIS and more aggressive breast cancer as observed in the Oncomine database of clinical breast cancer specimens.

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Zipper-interacting Protein Kinase (ZIPK) Modulates Canonical Wnt/β-Catenin Signaling through Interaction with Nemo-like Kinase and T-cell Factor 4 (NLK/TCF4)

Cited by 28 publications

References 33 publications

Wnt/β-catenin signalling: from plasma membrane to nucleus

Wnt/β-catenin signalling: from plasma membrane to nucleus

Clinical Comparison of Overlapping Deletions of 19p13.3

DAPK3 Suppresses Acini Morphogenesis and Is Required for Mouse Development

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