Affinage

TLK1

Serine/threonine-protein kinase tousled-like 1 · UniProt Q9UKI8

Length
766 aa
Mass
86.7 kDa
Annotated
2026-06-10
36 papers in source corpus 19 papers cited in narrative 19 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TLK1 is a nuclear serine/threonine kinase that coordinates chromatin maintenance, mitotic fidelity, and the DNA damage response (DDR) through phosphorylation of a defined set of substrates (PMID:9427565, PMID:18940270, PMID:37439356). In the DDR, TLK1 sits both downstream and upstream of checkpoint signaling: Chk1 is activated by DNA damage and phosphorylates/inactivates TLK1 (PMID:20581459), while TLK1 itself acts upstream of NEK1, phosphorylating it at T141 to activate an ATR>Chk1 cascade (PMID:30737777, PMID:30928383); this same NEK1 phosphorylation stabilizes VDAC1 to preserve mitochondrial integrity and limit apoptosis (PMID:31914854). At damage sites TLK1 is recruited via a non-canonical PIP-box that binds PCNA, and N-terminal hyper-autophosphorylation promoted by dimerization masks this PIP-box to suppress recruitment (PMID:39727191). TLK1 promotes repair by phosphorylating Rad9 at S328 to modulate 9-1-1 function and nucleosome reassembly at double-strand breaks (PMID:18940270) and RAD54 at T41/T59 (favoring homologous recombination) and T700 (delaying repair and creating a RAD51 interaction site) (PMID:37439356). In mitosis, TLK1 phosphorylates histone H3 to support chromosome condensation and segregation (PMID:14583098) and regulates myosin II regulatory light chain to ensure faithful chromosome integrity during division (PMID:18838128). Additional substrates link TLK1 to oncogenic signaling and motility: MK5 at S354 driving cell migration and invasion (PMID:35064619), AKTIP at T22/S237 to promote AKT activation (PMID:35366279), and YAP-Y407 phosphorylation (via NEK1) controlling YAP nuclear retention and transcriptional activity (PMID:39199688). A TLK1 missense variant (p.Q479E) that impairs kinase activity is associated with a neurodevelopmental disorder and produces elevated spontaneous DNA damage in patient-derived cells (PMID:38868186).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1997 Medium

    Established TLK1 as a nuclear serine/threonine kinase by identifying a functional NLS, defining where the enzyme acts.

    Evidence GST-NLS localization assay and transient transfection in COS-1 cells

    PMID:9427565

    Open questions at the time
    • No substrates or pathway context identified
    • Kinase activity not linked to a cellular process
  2. 2003 Medium

    Connected TLK1 to mitotic chromatin by showing it phosphorylates histone H3 and is required for proper chromosome condensation and segregation, defining its first chromosomal role.

    Evidence Kinase-dead dominant-negative overexpression, siRNA knockdown, immunofluorescence in breast epithelial cells

    PMID:14583098

    Open questions at the time
    • Direct H3 residue not mapped in this study
    • Mechanism linking H3 phosphorylation to condensation unresolved
  3. 2003 Medium

    Revealed a conserved role in transcription elongation in the C. elegans ortholog, broadening TLK function beyond mitosis.

    Evidence RNAi loss-of-function with RNAPII CTD-Ser2 phosphorylation and H3K36me readouts in C. elegans

    PMID:14614817

    Open questions at the time
    • Relevance to human TLK1 transcription not tested
    • No direct substrate in the elongation machinery identified
  4. 2005 Medium

    Identified the first RNA-related substrate, showing TLK1 phosphorylation of p68 helicase reduces its ssRNA affinity.

    Evidence In vitro kinase assay with immunoprecipitated p68 and gel-shift RNA-binding assay plus overexpression in HT1080

    PMID:15950181

    Open questions at the time
    • Phospho-site not mapped
    • In vivo functional consequence not established
  5. 2008 High

    Defined a direct DDR substrate by showing TLK1B phosphorylates Rad9 at S328 and promotes nucleosome reassembly at double-strand breaks, linking TLK1 to repair and chromatin restoration.

    Evidence Co-IP, in vitro kinase assay with S328A mutagenesis, Rad9-null complementation, and ChIP at HO-induced DSBs

    PMID:18940270

    Open questions at the time
    • Quantitative contribution of S328 to 9-1-1 loading unresolved
    • Interplay with Asf1 competition not fully dissected
  6. 2008 Medium

    Placed TLK1 upstream of myosin II during division by showing it controls MRLC phosphorylation required for chromosome integrity.

    Evidence RNAi knockdown with phosphomimetic DD-MRLC rescue and immunofluorescence

    PMID:18838128

    Open questions at the time
    • Direct MRLC phosphorylation by TLK1 not demonstrated
    • Intermediate kinases not excluded
  7. 2010 Medium

    Positioned TLK1 within checkpoint signaling by showing DNA damage activates Chk1, which phosphorylates and inactivates TLK1.

    Evidence Hypoxia-induced damage with western blot for Chk1 activation/TLK1 inactivation and Chk1 genetic manipulation

    PMID:20581459

    Open questions at the time
    • Chk1 phospho-sites on TLK1 not mapped here
    • Consequence of TLK1 inactivation for repair not quantified
  8. 2010 Medium

    Demonstrated a conserved cytokinesis role by linking TLK-1 to Aurora B (AIR-2) localization at midzone microtubules, with human TLK2 rescuing the ortholog.

    Evidence Time-lapse imaging of tlk-1 mutants, GFP localization, and TLK2 complementation in C. elegans

    PMID:20705056

    Open questions at the time
    • Mechanism of Aurora B recruitment by TLK unknown
    • Human TLK1-specific cytokinesis role not directly tested
  9. 2019 Medium

    Established the oncogenic TLK1>NEK1>ATR>Chk1 DDR axis and its druggability in prostate cancer after androgen deprivation.

    Evidence Kinase cascade western blots, thioridazine inhibition, colony assays, TMA IHC, TRAMP/PDX models

    PMID:30737777 PMID:30928383

    Open questions at the time
    • NEK1 T141 site mapping shown but downstream substrate breadth limited
    • Inhibitor specificity beyond TLK1 not fully resolved
  10. 2020 Medium

    Extended the TLK1>NEK1 axis to mitochondrial homeostasis, showing NEK1-T141 phosphorylation stabilizes VDAC1 and resists apoptosis.

    Evidence NEK1-T141A mutant, doxorubicin treatment, cytochrome C fractionation, and oxygen consumption assays in three cell lines

    PMID:31914854

    Open questions at the time
    • Direct NEK1-VDAC1 phosphorylation not mapped
    • Mitochondrial localization of the axis components not resolved
  11. 2020 Medium

    Provided a more selective TLK1 inhibitor (J54) confirming the kinase-dependence of the DDR axis in vivo.

    Evidence In vitro kinase assay, docking, cell viability, xenografts, dopamine receptor competition

    PMID:32905878

    Open questions at the time
    • Off-target profile incomplete
    • No co-crystal structure of TLK1-inhibitor complex
  12. 2021 Medium

    Linked TLK1 to AKT signaling by identifying AKTIP as a substrate (T22/S237) whose phosphorylation promotes AKT activation.

    Evidence Interactome analysis, phospho-site mapping, AKT phosphorylation readouts with AKTIP knockdown and J54 in prostate cancer cells

    PMID:35366279

    Open questions at the time
    • No in vitro reconstitution of direct phosphorylation
    • Mechanism by which AKTIP enhances PDK1-AKT association unresolved
  13. 2022 High

    Identified MK5 as a direct substrate (S354 critical) driving cell motility, connecting TLK1 to metastatic phenotypes.

    Evidence In vitro kinase assay, S354A mutagenesis, motility rescue in MK5-/- MEFs, phospho-specific antibody in cells and TMA

    PMID:35064619

    Open questions at the time
    • Roles of S160/S386 phosphorylation not dissected
    • Downstream MK5 effectors of motility not defined
  14. 2023 High

    Defined dual control of homologous recombination by mapping activating (T41/T59) and inhibitory (T700) RAD54 phosphorylation sites, with T700 revealing a RAD51 interaction surface.

    Evidence ISce-I HRR reporter, T41A/T59A/T700A mutagenesis, in vitro kinase assay, RAD51 interaction mapping

    PMID:37439356

    Open questions at the time
    • Temporal coordination of opposing phosphorylations unresolved
    • Structural basis of T700-driven RAD51 binding not determined
  15. 2023 Medium

    Connected TLK1 to chemoresistance via a UHRF2(pS643)>DNMT3A>ALOX15 epigenetic axis suppressing ferroptosis in gastric cancer.

    Evidence Co-IP, DNMT3A ubiquitination assay, rescue experiments, subcutaneous xenografts

    PMID:42149324

    Open questions at the time
    • Direct UHRF2-S643 phosphorylation by TLK1 not biochemically reconstituted
    • Generality beyond gastric cancer unknown
  16. 2024 High

    Resolved how TLK1 is recruited to damage and auto-regulated, showing dimerization-driven N-terminal autophosphorylation masks a PIP-box required for PCNA-dependent chromatin recruitment.

    Evidence Autophosphorylation mapping, PIP-box mutagenesis, PCNA Co-IP, laser microirradiation imaging

    PMID:39727191

    Open questions at the time
    • Signal triggering de-autophosphorylation/PIP-box exposure not identified
    • Kinetics of PCNA-dependent recruitment in repair not quantified
  17. 2024 Medium

    Extended the TLK1>NEK1 axis to Hippo signaling by showing it stabilizes nuclear YAP via Y407 phosphorylation and AR/TEAD1 co-activation.

    Evidence YAP-Y407F mutant, ChIP at ARE/TEAD1 promoters, nuclear/cytoplasmic fractionation, J54, LNCaP/VCaP xenografts

    PMID:39199688

    Open questions at the time
    • Whether NEK1 directly phosphorylates YAP-Y407 not established
    • TLK1 as a tyrosine-directed input unexplained
  18. 2024 Medium

    Linked TLK1 kinase function to human disease by showing a neurodevelopmental-disorder variant (p.Q479E) reduces activity and elevates spontaneous DNA damage.

    Evidence Biochemical kinase assay, proteomic interactions, comet assay, RNA-seq in patient-derived lymphoblasts

    PMID:38868186

    Open questions at the time
    • Causality between kinase deficit and neurodevelopmental phenotype not established in vivo
    • Which substrate losses drive the cellular phenotype unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TLK1 integrates its many substrates into stage-specific outputs—and what signal switches it between repair-promoting and repair-delaying activities—remains unresolved.
  • No structural model of substrate selection
  • Trigger for PIP-box exposure during the cell cycle unknown
  • Integration of mitotic, DDR, and oncogenic functions not unified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0140096 catalytic activity, acting on a protein 4 GO:0042393 histone binding 1
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 1
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-73894 DNA Repair 3 R-HSA-8953897 Cellular responses to stimuli 3

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 TLK1 (PKU-beta) encodes a nuclear serine/threonine protein kinase with a putative nuclear localization signal (NLS) in its N-terminal region; GST-fusion proteins containing the NLS localized efficiently to the nucleus, and transiently expressed PKU-beta in COS-1 cells was predominantly nuclear. GST-fusion nuclear localization assay, transient transfection in COS-1 cells, fluorescence in situ hybridization for chromosomal mapping Gene Medium 9427565
2003 TLK1 phosphorylates histone H3 in vitro and in vivo; expression of a kinase-dead TLK1B mutant in normal breast epithelial cells reduced phosphorylated histone H3, caused chromosome missegregation, aneuploidy, less condensed chromosomes at mitosis, and chromosome alignment/attachment failures. siRNA-mediated depletion of TLK1 caused a strong S-phase/G1 cell cycle block. Kinase-dead dominant negative overexpression, FACS, immunofluorescence microscopy, siRNA knockdown BMC cell biology Medium 14583098
2003 C. elegans TLK-1 (ortholog of human TLK1) is required for transcription elongation during development; TLK-1-deficient embryos showed dramatically reduced reporter gene expression and reduced phosphorylation of RNAPII CTD at Ser2 and methylation of histone H3 at Lys36. RNAi knockdown in C. elegans, reporter gene assays, western blot for RNAPII CTD phosphorylation and H3K36 methylation Current biology Medium 14614817
2005 TLK1 phosphorylates the DEAD-box RNA helicase p68; phosphorylation of the C-terminal fragment of p68 by recombinant TLK1 reduced its affinity to single-stranded RNA, and forced TLK1 overexpression in HT1080 cells increased phosphorylation of endogenous p68. In vitro kinase assay with immunoprecipitated p68, gel-shift RNA-binding assay, overexpression in HT1080 cells with western blot Biochemical and biophysical research communications Medium 15950181
2008 TLK1B binds Rad9 and phosphorylates it at S328; TLK1B overexpression hastens DSB repair and promotes nucleosome reassembly at DSBs by competing with Asf1 for binding to TLK1B; the kinase activity of TLK1B is dispensable for stimulation of chromatin remodeling at DSBs, but S328 phosphorylation of Rad9 increases wild-type Rad9's ability to complement radiation and doxorubicin sensitivity. Co-immunoprecipitation/pulldown, in vitro kinase assay (phosphorylation of hRad9-S328), complementation in Rad9-null mouse cells, HO nuclease-induced DSB chromatin reassembly assay, ChIP for Rad9 and Asf1 occupancy at DSB DNA repair High 18940270
2008 TLK1 (PKU-beta) regulates myosin II activity during mitosis; TLK1-depleted cells showed reduced phosphorylation of myosin II regulatory light chain (MRLC) at Ser19/Thr18, and expression of phosphomimetic DD-MRLC rescued chromosome segregation defects caused by TLK1 depletion, placing TLK1 upstream of MRLC phosphorylation for chromosome integrity. RNAi knockdown, western blot for MRLC phosphorylation, rescue with DD-MRLC expression, immunofluorescence Mutation research Medium 18838128
2010 Following DNA damage (severe hypoxia), Chk1 is activated and in turn phosphorylates/deactivates TLK1, placing TLK1 downstream of Chk1 in the DNA damage response checkpoint signaling cascade. Cell-based assay with hypoxia treatment, western blot for Chk1 activation and TLK1 inactivation, genetic manipulation of Chk1 Cell cycle Medium 20581459
2010 C. elegans TLK-1 functions in cytokinesis by localizing Aurora B (AIR-2) to midzone microtubules; tlk-1 mutants are defective in chromosome condensation, segregation, and cytokinesis, and human TLK2 could functionally substitute for tlk-1, suggesting evolutionarily conserved mitotic roles. Time-lapse microscopy of tlk-1 mutant embryos, GFP-localization studies, genetic complementation with human TLK2 Biochemical and biophysical research communications Medium 20705056
2019 Androgen deprivation of LNCaP cells results in increased TLK1B expression; TLK1 functions upstream of NEK1, which activates ATR and Chk1 in the DDR, establishing the axis: ADT > TLK1 > NEK1 > ATR > Chk1. TLK1 inhibition with thioridazine impairs ATR and Chk1 activation and leads to apoptosis. Western blot for kinase activation cascade, TLK1 inhibitor (thioridazine) treatment, colony formation assays, LNCaP xenografts International journal of cancer Medium 30737777
2019 TLK1 phosphorylates NEK1 at T141, activating it as part of the DDR; phosphorylation of Nek1-T141 was detectable in prostate cancer tissue microarrays and correlated with Gleason score, and TRAMP mice treated with thioridazine after castration failed to recover cancerous growth. In vivo TMA immunohistochemistry with pNek1-T141 antibody, TRAMP mouse model with thioridazine treatment, PDX model Cancer letters Medium 30928383
2020 TLK1 phosphorylates NEK1 at T141, and this activating phosphorylation contributes to NEK1-mediated phosphorylation and stabilization of VDAC1, maintaining mitochondrial integrity; cells expressing NEK1-T141A showed increased cytochrome C leakage, reduced oxygen consumption, and greater apoptosis upon doxorubicin treatment. Overexpression of NEK1-T141A mutant, doxorubicin treatment, subG1 FACS analysis, mitochondrial fractionation for cytochrome C, oxygen consumption measurement Cell cycle Medium 31914854
2020 The phenothiazine analog J54 acts as a potent inhibitor of TLK1 kinase activity (established by in vitro kinase assay and docking studies), inhibiting the TLK1>NEK1>ATR>Chk1 DDR axis and mediating apoptosis in prostate cancer cells and LNCaP xenografts. In vitro kinase assay, molecular docking, cell viability assays, xenograft model, dopamine receptor competition binding iScience Medium 32905878
2021 TLK1 interacts with and phosphorylates AKTIP at T22 and S237; TLK1-mediated AKTIP phosphorylation enhances the association of AKT with PDK1 and promotes AKT phosphorylation at T308 and S473, placing TLK1 upstream of AKT activation via AKTIP in prostate cancer cells. Interactome analysis identifying AKTIP as TLK1B substrate, western blot for AKT phosphorylation upon TLK1 inactivation and AKTIP knockdown, TLK1 inhibitor J54 treatment Pathophysiology Medium 35366279
2022 TLK1 directly phosphorylates MK5 (MAPK-activated protein kinase 5) at S160, S354, and S386, resulting in MK5 activation; specifically, phosphorylation at S354 is critical for MK5-driven cell motility, as MK5-S354A failed to restore motility in MK5-/- MEF cells, and TLK1-MK5 signaling promotes prostate cancer cell migration and invasion. In vitro kinase assay, phospho-site mutagenesis (S354A), motility assays (2D and 3D) in MK5-/- MEF rescue, HEK293 mobility shift assay, pMK5-S354 antiserum in LNCaP cells and IHC on TMA Molecular oncology High 35064619
2023 TLK1 phosphorylates RAD54 at T41, T59, and T700; phosphorylation at T41 and T59 (N-terminal domain) supports homologous recombination repair (HRR) and protects cells from DSB damage, whereas phosphorylation at T700 (C-terminal domain) impairs HRR and results in repair delay; T700 phosphorylation also reveals a new RAD54 interaction site with RAD51. TLK1 inhibition/depletion, ISce-I-GR-DsRed HRR reporter assay, phospho-site mutagenesis (T41A, T59A, T700A), in vitro kinase assay, RAD51 interaction studies Nucleic acids research High 37439356
2024 TLK1 (and TLK2) are hyper-autophosphorylated at their N-termini, mediated at least in part by homo- or hetero-dimerization; this hyper-autophosphorylation masks a conserved non-canonical PIP-box and suppresses TLK1 recruitment to damaged chromatin. Mutation of the PIP-box abolishes TLK1 recruitment to DNA damage sites, establishing that PCNA interaction via the PIP-box is required for TLK1 localization to damaged chromatin. Autophosphorylation mapping, PIP-box mutagenesis, PCNA co-immunoprecipitation, laser microirradiation/imaging of TLK1 recruitment to DNA damage sites Nucleic acids research High 39727191
2024 TLK1 variant p.Q479E (NDD-associated) impairs kinase activity without strongly altering localization or proximal protein interactions; patient-derived cells expressing this variant exhibit reduced cytokine responses and elevated spontaneous DNA damage but not increased radiation sensitivity or DNA repair defects. Biochemical kinase activity assay, proteomic interaction analysis, comet assay, flow cytometry, RNA-seq in patient-derived lymphoblasts iScience Medium 38868186
2024 TLK1>NEK1 axis promotes nuclear retention and transcriptional activation of YAP via stabilizing phosphorylation of YAP at Y407; J54 (TLK1 inhibitor) reverses YAP-Y407 phosphorylation, reduces nuclear YAP, enhances cytoplasmic YAP degradation, and disrupts YAP association with AR and TEAD1 co-activators at target gene promoters. Phospho-mutant expression (YAP-Y407F), ChIP assay for GFP-YAP at ARE- and TEAD1-driven promoters, nuclear/cytoplasmic fractionation, J54 inhibitor treatment, LNCaP and VCaP xenografts Cancers Medium 39199688
2023 TLK1 phosphorylates UHRF2 at Serine 643, which in turn suppresses ubiquitination-mediated degradation of DNMT3A; DNMT3A then decreases ALOX15 expression via methylation of its CpG island, establishing a TLK1 > UHRF2(pS643) > DNMT3A > ALOX15 axis that promotes cisplatin resistance in gastric cancer cells by suppressing ferroptosis. Co-immunoprecipitation for TLK1-UHRF2 and UHRF2-DNMT3A interactions, immunoprecipitation for DNMT3A ubiquitination, overexpression rescue experiments, subcutaneous xenograft model Chinese journal of integrative medicine Medium 42149324

Source papers

Stage 0 corpus · 36 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 Circular RNA TLK1 Aggravates Neuronal Injury and Neurological Deficits after Ischemic Stroke via miR-335-3p/TIPARP. The Journal of neuroscience : the official journal of the Society for Neuroscience 180 31311824
2008 Tousled homolog, TLK1, binds and phosphorylates Rad9; TLK1 acts as a molecular chaperone in DNA repair. DNA repair 63 18940270
2020 The circular RNA TLK1 exacerbates myocardial ischemia/reperfusion injury via targeting miR-214/RIPK1 through TNF signaling pathway. Free radical biology & medicine 57 32445866
2003 The C. elegans Tousled-like kinase (TLK-1) has an essential role in transcription. Current biology : CB 56 14614817
2021 Circular RNA TLK1 Promotes Sepsis-Associated Acute Kidney Injury by Regulating Inflammation and Oxidative Stress Through miR-106a-5p/HMGB1 Axis. Frontiers in molecular biosciences 51 34250012
2003 A dominant negative mutant of TLK1 causes chromosome missegregation and aneuploidy in normal breast epithelial cells. BMC cell biology 42 14583098
2019 Targeting the TLK1/NEK1 DDR axis with Thioridazine suppresses outgrowth of androgen independent prostate tumors. International journal of cancer 40 30737777
2019 The TLK1-Nek1 axis promotes prostate cancer progression. Cancer letters 37 30928383
2020 The TLK1/Nek1 axis contributes to mitochondrial integrity and apoptosis prevention via phosphorylation of VDAC1. Cell cycle (Georgetown, Tex.) 35 31914854
2020 Generation of Phenothiazine with Potent Anti-TLK1 Activity for Prostate Cancer Therapy. iScience 31 32905878
2023 TLK1-mediated RAD54 phosphorylation spatio-temporally regulates Homologous Recombination Repair. Nucleic acids research 24 37439356
2010 Exposure to acute hypoxia induces a transient DNA damage response which includes Chk1 and TLK1. Cell cycle (Georgetown, Tex.) 20 20581459
2008 PKU-beta/TLK1 regulates myosin II activities, and is required for accurate equaled chromosome segregation. Mutation research 14 18838128
2022 TLK1-mediated MK5-S354 phosphorylation drives prostate cancer cell motility and may signify distinct pathologies. Molecular oncology 12 35064619
1997 cDNA cloning and chromosomal mapping of genes encoding novel protein kinases termed PKU-alpha and PKU-beta, which have nuclear localization signal. Gene 12 9427565
2022 Circular RNA TLK1 Exerts Oncogenic Functions in Hepatocellular Carcinoma by Acting as a ceRNA of miR-138-5p. Journal of oncology 11 35359342
2021 Inhibiting of circ-TLK1 inhibits the progression of glioma through down-regulating PANX1 via targeting miR-17-5p. Journal of molecular histology 10 34181173
2022 The TLK1-MK5 Axis Regulates Motility, Invasion, and Metastasis of Prostate Cancer Cells. Cancers 9 36497211
2021 Interaction of TLK1 and AKTIP as a Potential Regulator of AKT Activation in Castration-Resistant Prostate Cancer Progression. Pathophysiology : the official journal of the International Society for Pathophysiology 9 35366279
2005 Identification of the human DEAD-box protein p68 as a substrate of Tlk1. Biochemical and biophysical research communications 7 15950181
2023 Exploiting TLK1 and Cisplatin Synergy for Synthetic Lethality in Androgen-Insensitive Prostate Cancer. Biomedicines 5 38001987
2024 De novo TLK1 and MDM1 mutations in a patient with a neurodevelopmental disorder and immunodeficiency. iScience 4 38868186
2023 The interaction between ASF1B and TLK1 promotes the malignant progression of low-grade glioma. Annals of medicine 4 36947060
2024 A novel approach to investigate the combinatorial effects of TLK1 (Tousled-Like Kinase1) inhibitors with Temozolomide for glioblastoma therapy. Bioorganic chemistry 3 39029318
2024 TLK1>Nek1 Axis Promotes Nuclear Retention and Activation of YAP with Implications for Castration-Resistant Prostate Cancer. Cancers 3 39199688
2010 Caenorhabditis elegans TLK-1 controls cytokinesis by localizing AIR-2/Aurora B to midzone microtubules. Biochemical and biophysical research communications 3 20705056
2025 Characterization of new non-ATP dependent inhibitors of TLK1 as potential molecules for treating prostate cancer. Bioorganic chemistry 2 40058222
2024 TLK1 Inhibition Enhances the Anticancer Effect of Deep UV Irradiation Through CHK1 Activation. Anticancer research 2 38925844
2023 Identification of a de novo mutation in TLK1 associated with a neurodevelopmental disorder and immunodeficiency. medRxiv : the preprint server for health sciences 2 37662408
2022 Circ_TLK1 knockdown alleviates oxygen-glucose deprivation/reoxygenation-induced PC12 cell injury by regulating microRNA-136-5p/follistatin like-1 axis. The European journal of neuroscience 2 35766911
2025 TLK1 as a therapeutic target in TMZ resistant glioblastoma using small molecule inhibitor. Scientific reports 1 40287404
2024 Autophosphorylation of the Tousled-like kinases TLK1 and TLK2 regulates recruitment to damaged chromatin via PCNA interaction. bioRxiv : the preprint server for biology 1 38712247
2026 Platycodin D Overcomes Cisplatin Resistance in Gastric Cancer by Inducing Ferroptosis through TLK1-Dependent UHRF2/DNMT3A/ALOX15 Pathway. Chinese journal of integrative medicine 0 42149324
2025 Autophosphorylation of the Tousled-like kinases TLK1 and TLK2 regulates recruitment to damaged chromatin via PCNA interaction. Nucleic acids research 0 39727191
2025 Targeting the TLK1-MK5 Axis Suppresses Prostate Cancer Metastasis. Cancers 0 40227796
2025 Mechanistic insights into Circ-MBOAT2-mediated regulation of TLK1 through miR-664b-3p in non-small cell lung cancer. Hereditas 0 40369698

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