ArticleThe Journal of biological chemistry2016
The Poly(ADP-ribose) Polymerase Enzyme Tankyrase Antagonizes Activity of the β-Catenin Destruction Complex through ADP-ribosylation of Axin and APC2.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Tankyrases and Their Binding Proteins: Origins of Their Roles in Diverse Cellular Pathways.Cells · 2026Review
- In Silico and In Vitro Analyses of Strawberry-Derived Extracts in Relation to Key Compounds' Metabolic and Anti-Tumor Effects.International journal of molecular sciences · 2025Article
- Establishment and validation of predictive models by mutational and transcriptional factors for the prognosis of stage IV colorectal cancer patients with liver metastasis who undergo palliative surgery on primary tumors.Translational cancer research · 2025Article
- Gut Microbiota, Deranged Immunity, and Hepatocellular Carcinoma.Biomedicines · 2024Review
- Why Is Wnt/β-Catenin Not Yet Targeted in Routine Cancer Care?Pharmaceuticals (Basel, Switzerland) · 2024Review
- Review
- Tankyrase inhibition interferes with junction remodeling, induces leakiness, and disturbs YAP1/TAZ signaling in the endothelium.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- E74‑like ETS transcription factor 5 facilitates cell proliferation through regulating the expression of adenomatous polyposis coli 2 in non‑small cell lung cancer.International journal of molecular medicine · 2023Article
- Article
- Functional roles of ADP-ribosylation writers, readers and erasers.Frontiers in cell and developmental biology · 2022Review
- Interplay between ADP-ribosyltransferases and essential cell signaling pathways controls cellular responses.Cell discovery · 2021Review
- Tankyrase inhibitors hinderParasitology · 2021Article
- Mutations and mechanisms of WNT pathway tumour suppressors in cancer.Nature reviews. Cancer · 2021Review
- FOXO4 Inhibits the Migration and Metastasis of Colorectal Cancer by Regulating theFrontiers in cell and developmental biology · 2021Article
- TDP-43, a protein central to amyotrophic lateral sclerosis, is destabilized by tankyrase-1 and -2.Journal of cell science · 2020Article
- Axin proteolysis by Iduna is required for the regulation of stem cell proliferation and intestinal homeostasis inDevelopment (Cambridge, England) · 2019Article
- Wnt/Beta-Catenin Signaling Regulation and a Role for Biomolecular Condensates.Developmental cell · 2019Review
- Novel insight into the function of tankyrase.Oncology letters · 2018Review
- miR-4326 promotes lung cancer cell proliferation through targeting tumor suppressor APC2.Molecular and cellular biochemistry · 2018Article
- Regulation of Wnt/β-catenin signalling by tankyrase-dependent poly(ADP-ribosyl)ation and scaffolding.British journal of pharmacology · 2017Review
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
Most colon cancer cases are initiated by truncating mutations in the tumor suppressor, adenomatous polyposis coli (APC). APC is a critical negative regulator of the Wnt signaling pathway that participates in a multi-protein "destruction complex" to target the key effector protein β-catenin for ubiquitin-mediated proteolysis. Prior work has established that the poly(ADP-ribose) polymerase (PARP) enzyme Tankyrase (TNKS) antagonizes destruction complex activity by promoting degradation of the scaffold protein Axin, and recent work suggests that TNKS inhibition is a promising cancer therapy. We performed a yeast two-hybrid (Y2H) screen and uncovered TNKS as a putative binding partner of Drosophila APC2, suggesting that TNKS may play multiple roles in destruction complex regulation. We find that TNKS binds a C-terminal RPQPSG motif in Drosophila APC2, and that this motif is conserved in human APC2, but not human APC1. In addition, we find that APC2 can recruit TNKS into the β-catenin destruction complex, placing the APC2/TNKS interaction at the correct intracellular location to regulate β-catenin proteolysis. We further show that TNKS directly PARylates both Drosophila Axin and APC2, but that PARylation does not globally regulate APC2 protein levels as it does for Axin. Moreover, TNKS inhibition in colon cancer cells decreases β-catenin signaling, which we find cannot be explained solely through Axin stabilization. Instead, our findings suggest that TNKS regulates destruction complex activity at the level of both Axin and APC2, providing further mechanistic insight into TNKS inhibition as a potential Wnt pathway cancer therapy.
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