ArticlePloS one2016
Tankyrase Inhibitors Stimulate the Ability of Tankyrases to Bind Axin and Drive Assembly of β-Catenin Degradation-Competent Axin Puncta.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Tankyrases and Their Binding Proteins: Origins of Their Roles in Diverse Cellular Pathways.Cells · 2026Review
- Selective Dual Inhibition of TNKS1 and CDK8 by TCS9725 Attenuates STAT1/β-Catenin/TGFβ1 Signaling in Renal Cancer.Current issues in molecular biology · 2025Article
- A genome-wide screen links peroxisome regulation with Wnt signaling through RNF146 and TNKS/2.The Journal of cell biology · 2024Article
- Analysis of Tumor-Associated AXIN1 Missense Mutations Identifies Variants That Activate β-Catenin Signaling.Cancer research · 2024Article
- A genome-wide screen links peroxisome regulation with Wnt signaling through RNF146 and tankyrase.bioRxiv : the preprint server for biology · 2024Article
- Principles and functions of condensate modifying drugs.Frontiers in molecular biosciences · 2022Review
- Tankyrase inhibitors hinderParasitology · 2021Article
- Reconstitution of the destruction complex defines roles of AXIN polymers and APC in β-catenin capture, phosphorylation, and ubiquitylation.Molecular cell · 2021Article
- Evaluation of AXIN1 and AXIN2 as targets of tankyrase inhibition in hepatocellular carcinoma cell lines.Scientific reports · 2021Article
- Triazole-Based Inhibitors of the Wnt/β-Catenin Signaling Pathway Improve Glucose and Lipid Metabolisms in Diet-Induced Obese Mice.Journal of medicinal chemistry · 2019Article
- Regulation of Wnt/β-catenin signalling by tankyrase-dependent poly(ADP-ribosyl)ation and scaffolding.British journal of pharmacology · 2017Review
- Molecular regulation and pharmacological targeting of the β-catenin destruction complex.British journal of pharmacology · 2017Review
- Differential Roles of AXIN1 and AXIN2 in Tankyrase Inhibitor-Induced Formation of Degradasomes and β-Catenin Degradation.PloS one · 2017Article
- Dual Roles for Membrane Association of Drosophila Axin in Wnt Signaling.PLoS genetics · 2016Article
- Tankyrase Sterile α Motif Domain Polymerization Is Required for Its Role in Wnt Signaling.Structure (London, England : 1993) · 2016Article
- Tankyrase Requires SAM Domain-Dependent Polymerization to Support Wnt-β-Catenin Signaling.Molecular cell · 2016Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the wnt signaling pathway is a major cause of colon cancer development. Tankyrase inhibitors (TNKSi) have recently been developed to block the wnt pathway by increasing axin levels to promote degradation of the wnt-regulator β-catenin. TNKSi bind to the PARP (poly(ADP)ribose polymerase) catalytic region of tankyrases (TNKS), preventing the PARylation of TNKS and axin that normally control axin levels through ubiquitination and degradation. TNKSi treatment of APC-mutant SW480 colorectal cancer cells can induce axin puncta which act as sites for assembly of β-catenin degradation complexes, however this process is poorly understood. Using this model system, we found that siRNA knockdown of TNKSs 1 and 2 actually blocked the ability of TNKSi drugs to induce axin puncta, revealing that puncta formation requires both the expression and the inactivation of TNKS. Immunoprecipitation assays showed that treatment of cells with TNKSi caused a strong increase in the formation of axin-TNKS complexes, correlating with an increase in insoluble or aggregated forms of TNKS/axin. The efficacy of TNKSi was antagonized by proteasome inhibitors, which stabilized the PARylated form of TNKS1 and reduced TNKSi-mediated assembly of axin-TNKS complexes and puncta. We hypothesise that TNKSi act to stimulate TNKS oligomerization and assembly of the TNKS-axin scaffold that form puncta. These new insights may help in optimising the future application of TNKSi in anticancer drug design.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.