ArticleNature communications2018
Molecular basis of Tousled-Like Kinase 2 activation.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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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.
The trial behind it
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Who cites it
29 citing papers in PubMed, 50 citations in OpenAlex.
- Co-Phosphoregulatory Network Underlying Functional Coherence of TLK1 and TLK2 Kinase Paralogs.International journal of molecular sciences · 2026Article
- Calcium overload induced mitochondrial and lysosomal dysfunction is regulated by Tousled-like kinase in a-synucleinopathy.Cell death & disease · 2026Article
- Targeting TLK2 with antisense oligonucleotides as a new strategy in acute myeloid leukemia.Frontiers in oncology · 2026Article
- Neuronal differentiation and activity drive nucleocytoplasmic shuttling of the intellectual disability kinase TLK2.Frontiers in cellular neuroscience · 2026Article
- Chromatin looping-based CRISPR screen identifies TLK2 as chromatin loop formation regulator in cancer stemness plasticity.Nature communications · 2025Article
- A TLK2-mediated calcium-driven cell death pathway links neuronal degeneration to nuclear envelope disruption.Nature communications · 2025Article
- Autophosphorylation of the Tousled-like kinases TLK1 and TLK2 regulates recruitment to damaged chromatin via PCNA interaction.Nucleic acids research · 2025Article
- Identification of modulators of the ALT pathway through a native FISH-based optical screen.Cell reports · 2025Article
- Tousled-like kinase loss confers PARP inhibitor resistance in BRCA1-mutated cancers by impeding non-homologous end joining repair.Molecular medicine (Cambridge, Mass.) · 2025Article
- Identification of Novel Modulators of the ALT Pathway Through a Native FISH-Based Optical Screen.bioRxiv : the preprint server for biology · 2024Article
- The TLK-ASF1 histone chaperone pathway plays a critical role in IL-1β-mediated AML progression.Blood · 2024Article
- Article
- Discovery and optimization of narrow spectrum inhibitors of Tousled like kinase 2 (TLK2) using quantitative structure activity relationships.European journal of medicinal chemistry · 2024Article
- Autophosphorylation of the Tousled-like kinases TLK1 and TLK2 regulates recruitment to damaged chromatin via PCNA interaction.bioRxiv : the preprint server for biology · 2024Article
- Case report: A novelFrontiers in genetics · 2024Article
- Discovery and Optimization of Narrow Spectrum Inhibitors of Tousled Like Kinase 2 (TLK2) Using Quantitative Structure Activity Relationships.bioRxiv : the preprint server for biology · 2023Article
- Untousling the Role of Tousled-like Kinase 1 in DNA Damage Repair.International journal of molecular sciences · 2023Review
- Loss of Nudt15 thiopurine detoxification increases direct DNA damage in hematopoietic stem cells.Scientific reports · 2023Article
- Targeting Prostate Cancer, the 'Tousled Way'.International journal of molecular sciences · 2023Review
- Overexpression of tousled-like kinase 2 predicts poor prognosis in HBV-related hepatocellular carcinoma patients after radical resection.Frontiers in genetics · 2023Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tousled-like kinases (TLKs) are required for genome stability and normal development in numerous organisms and have been implicated in breast cancer and intellectual disability. In humans, the similar TLK1 and TLK2 interact with each other and TLK activity enhances ASF1 histone binding and is inhibited by the DNA damage response, although the molecular mechanisms of TLK regulation remain unclear. Here we describe the crystal structure of the TLK2 kinase domain. We show that the coiled-coil domains mediate dimerization and are essential for activation through ordered autophosphorylation that promotes higher order oligomers that locally increase TLK2 activity. We show that TLK2 mutations involved in intellectual disability impair kinase activity, and the docking of several small-molecule inhibitors of TLK activity suggest that the crystal structure will be useful for guiding the rationale design of new inhibition strategies. Together our results provide insights into the structure and molecular regulation of the TLKs.
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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.