ReviewRSC advances2026
Disrupting the tumor-associated TNKS-USP25 protein-protein interface in cancer: structural basis, druggability, and therapeutic opportunities.
Review in RSC advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tankyrases (TNKS1/2) are multi-domain poly(ADP-ribose) polymerases that regulate Wnt/β-catenin signaling and broader cellular programs through both catalytic activity and extensive protein-protein interaction (PPI) networks. While most tankyrase-directed drug discovery has focused on inhibiting the PARP catalytic site, an emerging alternative is to target tankyrase stability by disrupting its interaction with the deubiquitinase USP25. USP25 functions as a positive regulator of tankyrase abundance by counteracting ubiquitin-dependent turnover; consequently, blocking the TNKS-USP25 PPI can reduce tankyrase levels, stabilize pathway antagonists such as AXIN, and dampen Wnt transcriptional output. In this review, we discuss current understanding of tankyrase domain architecture with emphasis on ankyrin repeat clusters (ARC1/2/4/5) that recognize short tankyrase-binding motifs (TBMs), and we highlight why ARC5 is a particularly actionable node for intervention in the TNKS-USP25 axis. We summarize the structural basis of USP25 recruitment
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Registered trials
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.