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Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

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The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
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Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
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Catenins01:23

Catenins

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Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
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Cell Specific Gene Expression01:58

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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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Related Experiment Video

Updated: Sep 13, 2025

Development of a Hepatitis B Virus Reporter System to Monitor the Early Stages of the Replication Cycle
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Wnt/β-Catenin Signaling Regulates Hepatitis B Virus cccDNA Levels.

Atsuya Ishida1, Sadahiro Iwabuchi2,3, Ying-Yi Li4

  • 1Department of Clinical Laboratory Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-0942, Japan.

International Journal of Molecular Sciences
|July 29, 2025
PubMed
Summary

Dedicator of cytokinesis 11 (DOCK11) and tankyrase (TNKS) regulate Hepatitis B virus (HBV) replication. Targeting DOCK11 and Wnt/β-catenin signaling may offer new therapies for persistent HBV infection.

Keywords:
DOCK11TNKSbeta-catenincccDNAhepatitis B virus

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Area of Science:

  • Hepatology
  • Virology
  • Molecular Biology

Background:

  • Hepatitis B virus (HBV) establishes persistent infections via nuclear covalently closed circular DNA (cccDNA).
  • Dedicator of cytokinesis 11 (DOCK11) was previously identified as a potential therapeutic target for reducing HBV cccDNA and HBV-DNA levels.
  • The role of tankyrase (TNKS), a DOCK11-associated gene regulating Wnt/β-catenin signaling, in the HBV life cycle was previously unknown.

Purpose of the Study:

  • To investigate the function of TNKS and Wnt/β-catenin signaling in the HBV life cycle.
  • To evaluate the therapeutic potential of targeting TNKS and Wnt/β-catenin signaling against HBV infection.

Main Methods:

  • Treatment of HBV-infected hepatocytes with TNKS and Wnt/β-catenin signaling inhibitors and agonists.
  • Evaluation of HBV life cycle using immunoprecipitation assays with DOCK11 and bulk RNA sequencing.
  • Assessment of SKL2001 and entecavir combination therapy in HBV-infected hepatocytes.

Main Results:

  • TNKS and Wnt/β-catenin signaling inhibitors significantly reduced HBV cccDNA and HBV-DNA levels.
  • Wnt/β-catenin signaling agonists generally enhanced the HBV life cycle.
  • DOCK11 directly binds to β-catenin, regulating HBV nuclear transport.
  • SKL2001, a Wnt/β-catenin agonist, strongly reduced cccDNA and, with entecavir, eradicated HBV without cytotoxicity.

Conclusions:

  • TNKS and Wnt/β-catenin signaling play crucial roles in the HBV life cycle.
  • DOCK11 and Wnt/β-catenin pathway molecules represent promising therapeutic targets for eliminating persistent HBV infection.