ArticleNature communications2021
TNK1 is a ubiquitin-binding and 14-3-3-regulated kinase that can be targeted to block tumor growth.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- TNK1 is a targetable JAK-independent driver of STAT signaling and inflammation.Genes & development · 2026Article
- Multiomics combined with machine learning defines unique molecular subtypes of cholangiocarcinoma and identifies TNK1 as a therapeutic target.Hepatology (Baltimore, Md.) · 2026Article
- Non-receptor tyrosine kinase signaling pathways and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Article
- Deep learning prioritizes cancer mutations that alter protein nucleocytoplasmic shuttling to drive tumorigenesis.Nature communications · 2025Article
- Integrating Clinical Cancer and PTM Proteomics Data Identifies a Mechanism of ACK1 Kinase Activation.Molecular cancer research : MCR · 2024Article
- Article
- In vitro safety evaluation of dopamine D3R antagonist, R-VK4-116, as a potential medication for the treatment of opioid use disorder.PloS one · 2024Article
- Fusion crystallization reveals the behavior of both the 1TEL crystallization chaperone and the TNK1 UBA domain.Structure (London, England : 1993) · 2023Article
- Computational analysis of regulatory regions in human protein kinases.Protein science : a publication of the Protein Society · 2023Article
- Kinase regulation by liquid-liquid phase separation.Trends in cell biology · 2023Review
- Fusion crystallization reveals the behavior of both the 1TEL crystallization chaperone and the TNK1 UBA domain.bioRxiv : the preprint server for biology · 2023Article
- Review
- Integrated regulation of dopaminergic and epigenetic effectors of neuroprotection in Parkinson's disease models.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Integration of Proteome-Wide PTM Data with Protein Structural and Sequence Features Identifies Phosphorylations that Mediate 14-3-3 Interactions.Journal of molecular biology · 2023Article
- Targeting AKT in ER-Positive HER2-Negative Metastatic Breast Cancer: From Molecular Promises to Real Life Pitfalls?International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
28 authors at 8 institutions in 2 countries.
Funding
Abstract
TNK1 is a non-receptor tyrosine kinase with poorly understood biological function and regulation. Here, we identify TNK1 dependencies in primary human cancers. We also discover a MARK-mediated phosphorylation on TNK1 at S502 that promotes an interaction between TNK1 and 14-3-3, which sequesters TNK1 and inhibits its kinase activity. Conversely, the release of TNK1 from 14-3-3 allows TNK1 to cluster in ubiquitin-rich puncta and become active. Active TNK1 induces growth factor-independent proliferation of lymphoid cells in cell culture and mouse models. One unusual feature of TNK1 is a ubiquitin-association domain (UBA) on its C-terminus. Here, we characterize the TNK1 UBA, which has high affinity for poly-ubiquitin. Point mutations that disrupt ubiquitin binding inhibit TNK1 activity. These data suggest a mechanism in which TNK1 toggles between 14-3-3-bound (inactive) and ubiquitin-bound (active) states. Finally, we identify a TNK1 inhibitor, TP-5801, which shows nanomolar potency against TNK1-transformed cells and suppresses tumor growth in vivo.
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Registered trials
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