ArticleCell death and differentiation2017
Differential requirements for Tousled-like kinases 1 and 2 in mammalian development.
Article in Cell death and differentiation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Knockdown of Tousled‑like kinase 1 inhibits survival of glioblastoma multiforme cells.International journal of molecular medicine · 2020Pooled it
- ASF1A: A versatile histone chaperone bridging chromatin dynamics, disease mechanisms and clinical potential (Review).Experimental and therapeutic medicine · 2026Review
- Co-Phosphoregulatory Network Underlying Functional Coherence of TLK1 and TLK2 Kinase Paralogs.International journal of molecular sciences · 2026Article
- Cryptic redundancy between PAR1b and PAR1a, two members of the PAR1 kinase family, in the survival of PAR1b-knockout mice.Scientific reports · 2026Article
- Genes with abnormal DNA methylation in chorionic villi of spontaneous abortions with monosomy X.Journal of assisted reproduction and genetics · 2026Article
- Neuronal differentiation and activity drive nucleocytoplasmic shuttling of the intellectual disability kinase TLK2.Frontiers in cellular neuroscience · 2026Article
- Targeting TLK2 with antisense oligonucleotides as a new strategy in acute myeloid leukemia.Frontiers in oncology · 2026Article
- A Tousled-like kinase (TLK) homolog required for male germline stem cell homeostasis in the planarian Schmidtea mediterranea.Developmental biology · 2026Article
- DNA-damage dependent isoform switching modulates RIF1 DNA repair complex assembly and phase separation.The Journal of biological chemistry · 2025Article
- Chromatin looping-based CRISPR screen identifies TLK2 as chromatin loop formation regulator in cancer stemness plasticity.Nature communications · 2025Article
- Mechanistic insights into Circ-MBOAT2-mediated regulation of TLK1 through miR-664b-3p in non-small cell lung cancer.Hereditas · 2025Article
- Autophosphorylation of the Tousled-like kinases TLK1 and TLK2 regulates recruitment to damaged chromatin via PCNA interaction.Nucleic acids research · 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
- Beyond the Horizon: Rethinking Prostate Cancer Treatment Through Innovation and Alternative Strategies.Cancers · 2024Article
- Article
- 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
- 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
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 5 countries.
Funding
Abstract
The regulation of chromatin structure is critical for a wide range of essential cellular processes. The Tousled-like kinases, TLK1 and TLK2, regulate ASF1, a histone H3/H4 chaperone, and likely other substrates, and their activity has been implicated in transcription, DNA replication, DNA repair, RNA interference, cell cycle progression, viral latency, chromosome segregation and mitosis. However, little is known about the functions of TLK activity in vivo or the relative functions of the highly similar TLK1 and TLK2 in any cell type. To begin to address this, we have generated Tlk1- and Tlk2-deficient mice. We found that while TLK1 was dispensable for murine viability, TLK2 loss led to late embryonic lethality because of placental failure. TLK2 was required for normal trophoblast differentiation and the phosphorylation of ASF1 was reduced in placentas lacking TLK2. Conditional bypass of the placental phenotype allowed the generation of apparently healthy Tlk2-deficient mice, while only the depletion of both TLK1 and TLK2 led to extensive genomic instability, indicating that both activities contribute to genome maintenance. Our data identifies a specific role for TLK2 in placental function during mammalian development and suggests that TLK1 and TLK2 have largely redundant roles in genome maintenance.
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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.