Affinage

PBK

Lymphokine-activated killer T-cell-originated protein kinase · UniProt Q96KB5

Length
322 aa
Mass
36.1 kDa
Annotated
2026-04-29
100 papers in source corpus 34 papers cited in narrative 34 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PBK (also called TOPK) is a mitotic serine/threonine kinase that integrates cell-cycle progression, checkpoint signaling, and chromatin regulation by phosphorylating a broad array of substrates downstream of CDK1/cyclin B1 activation. CDK1 phosphorylates PBK at Thr9, Thr24, Ser32, and Ser59 during mitosis, and Src/FYN phosphorylate it at Tyr74 and Tyr272 to increase its stability and activity; once active, PBK phosphorylates p38 MAPK, ERK2 (forming a positive feedback loop), PRC1, LGN/GPSM2, histone H3, C2H2 zinc-finger protein linkers, c-Jun, IκBα, ULK1, Prx1, YB1, MSL1, PTEN, TRIM37, and PRPK, thereby controlling spindle midzone formation, cytokinesis, the DNA replication stress checkpoint, NF-κB and AP-1 transcriptional programs, autophagy suppression, and antioxidant defense (PMID:15541388, PMID:17631144, PMID:17512944, PMID:17160018, PMID:25575812, PMID:18, PMID:33431797, PMID:24012691, PMID:31378785, PMID:37016377). PBK also binds the DNA-binding domain of p53 and suppresses its transactivation function, linking PBK to p53-dependent tumor suppression and drug resistance (PMID:20622899, PMID:32237067). Through these activities PBK is essential for proliferation of neural progenitor cells and spermatocytes and drives tumorigenesis, metastasis, and multi-drug resistance across diverse cancer types (PMID:16291951, PMID:16316408, PMID:26745678, PMID:35859118).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2004 High

    Establishing PBK as a CDK1-activated mitotic kinase required for cytokinesis resolved its cell-cycle phase of action and placed it at the spindle midzone, a critical structure for cell division.

    Evidence Phospho-site mapping (Thr9 by CDK1/cyclin B), immunofluorescence at spindle midzone, siRNA knockdown causing cytokinesis failure in HeLa cells

    PMID:15541388

    Open questions at the time
    • Mechanism by which PBK promotes midzone assembly not defined
    • Other CDK1 phosphorylation sites on PBK not yet mapped at this time
  2. 2005 High

    Identification of p38 MAPK as a direct PBK substrate linked PBK to DNA damage signaling and demonstrated its role in neural progenitor proliferation, extending PBK function beyond cancer cells to normal stem cell biology.

    Evidence In vitro kinase assay, siRNA knockdown reducing p38 activation and γ-H2AX, pharmacological inhibition and transgenic ablation in mouse neural progenitors

    PMID:16291951 PMID:17160018

    Open questions at the time
    • Phosphorylation sites on p38 targeted by PBK not mapped
    • Relative contribution of PBK versus canonical MKKs to p38 activation unclear
  3. 2007 High

    Discovery of the PBK–ERK2 positive feedback loop and the PBK–CDK1–PRC1 ternary complex established PBK as a signaling hub that both amplifies MAPK cascades and cooperatively regulates mitotic microtubule bundling.

    Evidence Bidirectional in vitro kinase assays between PBK and ERK2 with epistatic knockdowns; ternary complex reconstitution showing PBK enhances CDK1-dependent PRC1-T481 phosphorylation

    PMID:17512944 PMID:17631144

    Open questions at the time
    • Direct PBK phosphorylation sites on ERK2 not mapped
    • Structural basis of ternary PBK–CDK1–PRC1 complex unknown
  4. 2010 High

    Three new direct substrates—LGN/GPSM2 (Thr450), Prx1 (Ser32), and the p53 DNA-binding domain interaction—expanded PBK's roles to spindle orientation, antioxidant defense, and tumor suppressor antagonism, respectively.

    Evidence In vitro kinase assays with phospho-site identification for LGN and Prx1; reciprocal Co-IP and yeast two-hybrid for p53-DBD binding; CD spectroscopy for Prx1 structural change; p21 upregulation upon PBK knockdown

    PMID:20589935 PMID:20622899 PMID:20647304

    Open questions at the time
    • Whether PBK directly phosphorylates p53 or only binds it was not resolved
    • In vivo relevance of Prx1-S32 phosphorylation beyond melanoma not tested
  5. 2012 High

    Development of HI-TOPK-032 as a selective PBK inhibitor provided a pharmacological tool confirming that PBK kinase activity drives ERK-RSK signaling and survival in colon cancer, validating PBK as a druggable target.

    Evidence In vitro kinase assay showing selectivity over ERK1/JNK1/p38, xenograft tumor suppression, apoptosis markers

    PMID:22523035

    Open questions at the time
    • Off-target effects of HI-TOPK-032 not comprehensively profiled
    • Clinical translation not addressed
  6. 2013 High

    The CHFR–PBK–PTEN–Akt axis revealed that PBK is both regulated by E3-ligase-mediated ubiquitination and itself inactivates PTEN by phosphorylation, connecting PBK to PI3K/Akt signaling and mitotic checkpoint control.

    Evidence In vitro ubiquitination and kinase assays, siRNA epistasis linking CHFR to PBK levels and PBK to PTEN phosphorylation

    PMID:24012691

    Open questions at the time
    • PTEN phosphorylation sites by PBK not mapped
    • Whether CHFR ubiquitinates PBK via K48 or K63 chains not determined
  7. 2014 Medium

    Demonstration that PBK phosphorylates IκBα to activate NF-κB-dependent iNOS expression established PBK as a pro-inflammatory kinase operating outside its canonical mitotic context.

    Evidence Co-IP, in vitro kinase assay for IκBα, NF-κB reporter assay, siRNA abolishing LPS-induced iNOS

    PMID:24440499

    Open questions at the time
    • IκBα phosphorylation sites by PBK not identified
    • Whether PBK activates NF-κB independently of IKK complex not resolved
    • Single-lab finding
  8. 2015 High

    Identification of PBK as the master kinase phosphorylating C2H2 zinc-finger protein linkers during mitosis explained the coordinate chromatin dissociation of hundreds of ZFPs, revealing a major role in mitotic chromatin reorganization.

    Evidence Biotinylated kinase-inhibitor affinity purification identifying PBK, in vitro kinase assay with ZFP substrates, temporal correlation with CDK1 activation

    PMID:25575812

    Open questions at the time
    • Functional consequence of ZFP chromatin dissociation for gene bookmarking or re-activation post-mitosis not determined
    • Full spectrum of ZFP substrates not catalogued
  9. 2016 High

    Src-mediated tyrosine phosphorylation of PBK at Y74 and Y272 was shown to stabilize PBK protein and enhance its histone H3 kinase activity, while PBK was found to directly phosphorylate c-Jun at Ser63/73 to activate AP-1, linking upstream tyrosine kinase input to downstream transcriptional output.

    Evidence In vitro kinase assays, Src KO MEFs, pulse-chase stability, Co-IP of PBK–c-Jun, AP-1 reporter, xenograft models

    PMID:26745678 PMID:27016416

    Open questions at the time
    • Relative contributions of Src versus FYN to PBK Y74/Y272 phosphorylation in different tissues not compared
    • Structural basis of Src–PBK interaction unknown
  10. 2017 High

    Comprehensive CDK1 phospho-mapping of PBK (Thr9, Thr24, Ser32, Ser59) revealed that CDK1-mediated phosphorylation paradoxically restrains PBK's oncogenic function, with the non-phosphorylatable T9A mutant being more tumorigenic than wild-type.

    Evidence In vitro kinase assay, phospho-mapping, mutant overexpression with tumorigenesis assays in breast cancer cells

    PMID:28780319

    Open questions at the time
    • Mechanism by which T9 phosphorylation suppresses oncogenic activity not elucidated
    • Whether CDK1 phosphorylation affects PBK substrate selectivity untested
  11. 2019 High

    PBK was shown to directly phosphorylate ULK1 at three sites (S469/S495/S533) to inhibit autophagy initiation, establishing PBK as a negative regulator of autophagy and explaining its role in temozolomide resistance in glioma.

    Evidence In vitro kinase assay with phospho-site mapping, autophagy flux assays, drug sensitivity assays in glioma cells

    PMID:31378785

    Open questions at the time
    • Whether PBK inhibits autophagy through ULK1 in non-cancer contexts not tested
    • Relative importance of each ULK1 phospho-site not dissected
  12. 2020 Medium

    PBK was placed in the replication stress checkpoint through its interaction with CHK1 and Cdc25c, with PBK depletion causing replication fork collapse, extending PBK's roles from mitosis into S-phase DNA integrity.

    Evidence Co-IP of PBK with CHK1/Cdc25c, DNA fiber assays showing increased fork stalling upon PBK siRNA, ssDNA foci, xenograft with fractionated irradiation

    PMID:33168956

    Open questions at the time
    • Whether PBK directly phosphorylates CHK1 or Cdc25c not determined
    • Mechanism of PBK recruitment to stalled forks unknown
    • Single-lab finding
  13. 2021 High

    PBK was shown to phosphorylate MSL1, enhancing MSL complex assembly and H4K16 acetylation at target promoters such as CD276, revealing an epigenetic effector role; separately, a Pbk kinase-dead knock-in mouse demonstrated that PBK kinase activity is required for menin-inhibitor-induced pancreatic beta cell proliferation.

    Evidence In vitro kinase assay and ChIP for MSL1/CD276; Pbk kinase-deficiency knock-in mouse with HFD model and menin inhibitor pharmacology

    PMID:33431797 PMID:33821572

    Open questions at the time
    • MSL1 phosphorylation sites not mapped
    • Whether PBK-MSL1 axis operates outside nasopharyngeal carcinoma not tested
    • Downstream mediators of PBK in beta cell proliferation beyond kinase requirement not identified
  14. 2022 Medium

    Identification of ERK2 phosphorylation of PBK at Ser32 (in addition to CDK1-mediated Thr9) linked PBK activation to drug resistance signaling via HGF/c-Met, while PBK was shown to phosphorylate TRIM37 to activate NF-κB and confer PARP inhibitor resistance.

    Evidence In vitro kinase assay for ERK2→PBK-S32, phospho-specific antibody in sorafenib-resistant RCC; Co-IP of PBK–TRIM37 with nuclear translocation and drug resistance assays in ovarian cancer

    PMID:35546143 PMID:35859118

    Open questions at the time
    • Whether ERK2- and CDK1-mediated S32 phosphorylation are functionally redundant untested
    • TRIM37 phosphorylation sites not mapped
    • Clinical relevance of PBK in PARP inhibitor resistance needs validation
  15. 2023 High

    FYN kinase was identified as a second Src-family kinase phosphorylating PBK at Y272, and phosphoproteomics in TOPK-knockout mice identified HSPB1-Ser15 as a downstream substrate; separately, PBK was shown to phosphorylate YB1 at Thr89/Ser209 to drive eEF1A1 transcription and AKT/mTOR activation.

    Evidence Isotope kinase assay for FYN→PBK-Y272, phosphoproteomics in KO mice identifying HSPB1; in vitro kinase assay for PBK→YB1 with ChIP and rescue experiments

    PMID:37016377 PMID:37328464

    Open questions at the time
    • Full phosphoproteomic landscape of PBK-dependent substrates in vivo not yet catalogued beyond HSPB1
    • Structural basis for PBK's broad substrate recognition unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Despite extensive substrate identification, the structural basis for PBK's unusually broad substrate specificity, its consensus phosphorylation motif, and the tissue-specific regulatory logic that selects among its many substrates remain unresolved.
  • No crystal or cryo-EM structure of PBK available
  • No defined consensus phosphorylation motif
  • Systematic comparison of substrate selectivity across tissues not performed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 19
Localization
GO:0005634 nucleus 2 GO:0005694 chromosome 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-162582 Signal Transduction 8 R-HSA-1640170 Cell Cycle 7 R-HSA-4839726 Chromatin organization 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-73894 DNA Repair 2 R-HSA-9612973 Autophagy 2
Partners
CDK1ERK2FYNPRC1PRKWNK1SRCTP53ULK1

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 TOPK/PBK is phosphorylated at Thr-9 by cdk1/cyclin B during mitosis, associates with mitotic spindles, and is required for formation of the spindle midzone and cytokinesis; knockdown of TOPK disrupts spindle midzone formation and cytokinesis. Immunofluorescence, Western blot, kinase assay, siRNA knockdown with phenotypic readout Biochemical and biophysical research communications High 15541388
2007 TOPK and ERK2 form a positive feedback loop: TOPK phosphorylates ERK2 and ERK2 phosphorylates TOPK; knockdown of either reduces phosphorylation of the other and downstream ERK2 substrates in HCT116 colorectal cancer cells. In vitro kinase assay, siRNA knockdown, EGF-stimulation Western blot, transient transfection Gastroenterology High 17631144
2007 TOPK enhances cdk1/cyclin B1-dependent phosphorylation of the microtubule-bundling protein PRC1 at T481 during mitosis by forming a ternary complex with cdk1/cyclin B1 and PRC1 on microtubules; TOPK enzymatic activity and its association with PRC1 are both required, but TOPK cannot phosphorylate PRC1 directly in vitro without cdk1/cyclin B1. In vitro kinase assay, Co-IP, in vivo phosphorylation assay, dominant-negative constructs Journal of molecular biology High 17512944
2005 PBK/TOPK phosphorylates p38 MAPK and is required for appropriate p38 activation by growth factors; PBK knockdown impairs p38 activation, reduces cell motility, and impairs DNA damage response (reduced γ-H2AX, increased DNA damage). siRNA knockdown, Western blot, kinase assay, soft agar growth assay Oncogene High 17160018
2005 PBK/TOPK is expressed in proliferating neural progenitor cells and phosphorylates p38 MAPK in a cell-cycle-dependent manner; inhibition of the PBK/TOPK–p38 pathway disrupts neural progenitor proliferation and self-renewal in vitro and in vivo. Microarray profiling, in vitro kinase assay, pharmacological inhibition, transgenic ablation/lineage tracing in mice The Journal of neuroscience High 16291951
2005 TOPK is expressed in spermatocytes and spermatids; TOPK-Thr-9 is specifically phosphorylated by cdk1/cyclin B during both mitotic and meiotic phases, while Thr-198 (ATP pocket) is constitutively phosphorylated, indicating a role in cytokinesis/chromosomal segregation during spermatogenesis. Immunofluorescence in situ, phospho-specific antibodies, Western blot Development, growth & differentiation Medium 16316408
2010 PBK/TOPK physically interacts with the DNA-binding domain (DBD) of tumor suppressor p53 in HCT116 cells; this interaction suppresses p53 transactivation function, reducing expression of p21 and other p53 target genes; PBK knockdown upregulates p21 particularly after genotoxic damage. Co-immunoprecipitation, yeast two-hybrid, gene knockdown with microarray analysis Oncogene High 20622899
2010 PBK/TOPK phosphorylates LGN/GPSM2 at Thr450 during mitosis; overexpression of a T450A phosphorylation-deficient mutant causes aberrant chromosomal segregation and growth suppression in breast cancer cells. In vitro kinase assay, Western blot (G2/M-enriched lysates), siRNA, mutant overexpression with phenotypic readout Genes, chromosomes & cancer High 20589935
2010 TOPK binds peroxiredoxin 1 (Prx1) and phosphorylates it at Ser-32, altering Prx1's secondary structure and enhancing its peroxidase activity; this phosphorylation prevents UVB-induced H2O2 accumulation and apoptosis in melanoma cells. LC-MS/MS binding identification, in vitro kinase assay, CD spectroscopy, immunofluorescence, siRNA/stable mutant lines, flow cytometry The Journal of biological chemistry High 20647304
2012 HI-TOPK-032 directly inhibits TOPK kinase activity in vitro with selectivity over ERK1, JNK1, and p38; in cells it reduces ERK-RSK phosphorylation and increases apoptosis via p53, cleaved caspase-7, and cleaved PARP; suppresses tumor growth in colon cancer xenograft in vivo. In vitro kinase assay screen, Western blot, xenograft model Cancer research High 22523035
2013 CHFR (E3 ubiquitin ligase) ubiquitinates TOPK and regulates its protein levels; TOPK in turn phosphorylates and inactivates PTEN, leading to Akt activation and G2/M progression; this CHFR–TOPK–PTEN–Akt axis regulates the mitotic checkpoint. Co-IP, in vitro kinase/ubiquitination assay, siRNA epistasis, phospho-Western blot Cellular signalling High 24012691
2015 TOPK/PBK is the master mitotic kinase that phosphorylates the conserved linker motif of C2H2 zinc finger proteins (ZFPs), driving their coordinate dissociation from condensing chromatin during mitosis; TOPK is activated by Cdk1 with precise temporal correlation to ZFP linker phosphorylation. Biotinylated kinase inhibitor (K252a) affinity purification, in vitro kinase assay with ZFP substrates, pharmacological and genetic inhibition Oncotarget High 25575812
2016 Src kinase directly binds and phosphorylates TOPK at Tyr74 and Tyr272; these phosphorylations increase TOPK stability by reducing its ubiquitination, elevate TOPK kinase activity toward histone H3 (Ser10), and promote colon cancer tumorigenesis. In vitro kinase assay, phospho-specific antibody generation, Co-IP, pulse-chase stability assay, Src KO MEF comparison, xenograft model Oncotarget High 27016416
2016 TOPK directly binds and phosphorylates c-Jun, activating AP-1 transcription of CCND1 and CDC2, thereby conferring resistance of NSCLC cells to EGFR-TKI gefitinib. Co-IP, in vitro kinase assay, reporter assay, siRNA knockdown, xenograft model Oncotarget High 26745678
2017 CDK1 phosphorylates PBK at Thr-9, Thr-24, Ser-32, and Ser-59 during mitosis in vitro and in cells; phosphorylation of Thr-9 is specifically involved in cytokinesis, and the non-phosphorylatable PBK-T9A mutant exhibits greater tumor-promoting activity than wild-type PBK, indicating CDK1-mediated phosphorylation inhibits PBK's oncogenic function. In vitro kinase assay, phosphomapping, mutant overexpression, tumorigenesis assays in breast cancer cells Cellular signalling High 28780319
2018 TOPK promotes microglia/macrophage M2 polarization by binding to HDAC1 and HDAC2 and promoting their phosphorylation; TOPK overexpression increases M2 markers (CD206, Arg1) and reduces M1 inflammatory cytokines; effects are reversed by HDAC1/2 inhibitor FK228, placing TOPK upstream of HDAC1/2 in anti-inflammatory signaling after cerebral ischemia. Co-IP (in vivo binding), Western blot, siRNA/overexpression in BV2 cells, MCAO mouse model Aging and disease Medium 29896413
2018 TOPK is phosphorylated and activated by solar UV; it directly phosphorylates c-Jun at Ser63 and Ser73 in a JNK-independent manner, activating AP-1 and promoting skin carcinogenesis. In vitro kinase assay, phospho-specific Western blot, siRNA knockdown, mouse skin carcinogenesis model Oncogene High 32277233
2018 TOPK phosphorylates PRPK (p53-related protein kinase); knockdown of TOPK inhibits PRPK phosphorylation and confers resistance to solar UV-induced skin carcinogenesis in mouse models. In vitro/cell kinase assay, siRNA knockdown, mouse skin carcinogenesis model, FDA-approved drug PRPK inhibitors Oncogene Medium 29904102
2019 TOPK directly binds and phosphorylates ULK1 at Ser469, Ser495, and Ser533, decreasing ULK1 activity and stability, thereby inhibiting autophagy initiation in glioma cells and contributing to temozolomide resistance. Co-IP, in vitro kinase assay, phospho-site mapping, Western blot, autophagy flux assay, drug sensitivity assay Cell death & disease High 31378785
2019 PBK promotes HCC metastasis via the ETV4–uPAR signaling pathway: PBK enhances binding of transcription factor ETV4 to the uPAR promoter (shown by ChIP assay), increasing uPAR expression; uPAR overexpression rescues the metastasis suppressed by PBK knockdown. Chromatin immunoprecipitation (ChIP), luciferase promoter assay, gain/loss-of-function, orthotopic mouse model Cancer letters Medium 30914208
2019 MET tyrosine kinase phosphorylates TOPK at Tyr74, preventing apoptosis in gefitinib-resistant NSCLC cells; this is downstream of the COX2-TXA2 pathway regulating MET via AP-1. Western blot, phospho-antibody detection, Co-IP, cell viability assays, in vitro and ex vivo validation Cell death & disease Medium 31611604
2020 PBK/TOPK mediates paclitaxel resistance in H460 NSCLC cells by promoting p53 nuclear export and ubiquitination, thereby suppressing p53-dependent autophagic cell death. siRNA knockdown, Western blot for nuclear/cytoplasmic fractionation, ubiquitination assay, LC3 puncta imaging, flow cytometry FEBS open bio Medium 32237067
2021 PBK phosphorylates MSL1 and enhances the interaction of MSL1 with MSL2, MSL3, and KAT8 (components of the MSL complex), promoting MSL complex enrichment on the CD276 promoter, leading to increased histone H4 K16 acetylation and CD276 transcription in nasopharyngeal carcinoma. Co-IP, in vitro kinase assay, ChIP, reporter assay, siRNA knockdown Oncogenesis High 33431797
2021 Menin/JunD/HDAC3 complex represses PBK expression by reducing histone H3 acetylation at the PBK promoter; menin inhibitor disrupts the menin-JunD interaction, derepresses PBK, and promotes beta cell proliferation in HFD-induced diabetic mice; Pbk kinase activity (knock-in deficiency model) is required for menin-inhibitor-induced beta cell proliferation. Pbk kinase-deficiency knock-in mouse model, ChIP, Co-IP, menin inhibitor pharmacology, HFD mouse model EMBO molecular medicine High 33821572
2022 ERK2 phosphorylates TOPK at Ser32 (a novel site in addition to Thr9); pTOPK(S32) is associated with sorafenib resistance in renal cell carcinoma; HGF/c-Met signaling activates p-TOPK(S32) during resistance development. In vitro kinase assay, phospho-specific antibody, Western blot, drug resistance cell models Cell death & disease Medium 35546143
2022 PBK directly interacts with TRIM37 and promotes its phosphorylation and nuclear translocation, activating the NFκB pathway and conferring PARP inhibitor resistance in ovarian cancer. Co-IP, Western blot for phosphorylation and nuclear translocation, siRNA/overexpression, in vitro and in vivo drug resistance assays Experimental & molecular medicine Medium 35859118
2022 PBK directly phosphorylates histone H3 (in vitro reconstitution) and promotes CDH1 phosphorylation at S840/S846/S847 in cells (indirectly, as PBK failed to phosphorylate CDH1 directly in vitro), stabilizing CDH1 and suppressing Wnt/β-catenin signaling to inhibit CRC cell migration and invasion. In vitro kinase assay with recombinant PBK and HH3, phospho-CDH1 Western blot, siRNA/overexpression, migration/invasion assays Frontiers in pharmacology Medium 35115926
2023 FYN tyrosine kinase directly binds and phosphorylates TOPK at Y272; the TOPK-272F mutation abolishes this phosphorylation and interaction; FYN–TOPK axis promotes gastric cancer progression by phosphorylating HSPB1 at Ser15 as identified by phosphoproteomics in TOPK-knockout mice. Co-IP, pull-down assay, in vitro kinase assay with 32P isotope, phospho-specific antibody generation, phosphoproteomics, TOPK knockout mice, immunofluorescence co-localization Journal of experimental & clinical cancer research High 37016377
2023 TOPK phosphorylates YB1 at Thr89 and Ser209; phosphorylated YB1 binds the eEF1A1 promoter to activate its transcription, leading to AKT/mTOR signaling activation and esophageal cancer cell proliferation. In vitro kinase assay, ChIP, reporter assay, TOPK KO, rescue experiments, xenograft model Cell death & disease High 37328464
2020 TOPK directly interacts with CHK1 and Cdc25c; TOPK depletion increases fork stalling and collapse under replication stress, impairs recovery from replication fork stalling, and increases replication-associated single-stranded DNA foci, placing TOPK in the S-phase checkpoint signaling pathway. Co-IP, siRNA knockdown, DNA fiber assay, ssDNA immunofluorescence, cancer cell xenograft with fractionated irradiation Cell death and differentiation Medium 33168956
2014 TOPK promotes NF-κB-dependent iNOS gene expression and nitric oxide production in response to LPS: TOPK interacts with IκBα and phosphorylates it, promoting NF-κB transcriptional activity; knockdown abolishes LPS-induced iNOS and NF-κB promoter activity. Co-IP, in vitro kinase assay for IκBα, reporter assay, siRNA knockdown, NOS expression Western blot Cellular signalling Medium 24440499
2015 PBK/TOPK enhances aggressive phenotype in prostate cancer through β-catenin–TCF/LEF-mediated upregulation of MMP-2 and MMP-9 transcription; gain- and loss-of-function studies show PBK modulates invasive ability causally. siRNA/overexpression, promoter reporter assay, invasion assay, tissue array Oncotarget Medium 25909225
2015 Geranylgeranylation regulates PBK expression in breast cancer cells via YAP (Yes-associated protein) as mediator; atorvastatin or GGTI-298 downregulates PBK through YAP inactivation, identifying PBK as a downstream target of the Hippo-YAP pathway. shRNA knockdown, Western blot, cell proliferation assay, pharmacological inhibition Cancer cell international Medium 25745361
2012 c-Myc regulates PBK expression through E2F1 in high-grade lymphomas; inhibition of c-Myc or E2F1 decreases PBK expression and cell growth, establishing a c-Myc–E2F1–PBK transcriptional axis. ChIP (implied), Western blot, siRNA knockdown, cell viability assay Leukemia research Medium 23237560

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Bidirectional signals transduced by TOPK-ERK interaction increase tumorigenesis of HCT116 colorectal cancer cells. Gastroenterology 127 17631144
2006 PBK/TOPK promotes tumour cell proliferation through p38 MAPK activity and regulation of the DNA damage response. Oncogene 124 17160018
2002 Rice SPK, a calmodulin-like domain protein kinase, is required for storage product accumulation during seed development: phosphorylation of sucrose synthase is a possible factor. The Plant cell 118 11910009
2009 Stable interference of EWS-FLI1 in an Ewing sarcoma cell line impairs IGF-1/IGF-1R signalling and reveals TOPK as a new target. British journal of cancer 111 19491900
2010 PBK/TOPK interacts with the DBD domain of tumor suppressor p53 and modulates expression of transcriptional targets including p21. Oncogene 102 20622899
2001 PBK/TOPK is a novel mitotic kinase which is upregulated in Burkitt's lymphoma and other highly proliferative malignant cells. Blood cells, molecules & diseases 101 11783945
2012 Novel TOPK inhibitor HI-TOPK-032 effectively suppresses colon cancer growth. Cancer research 93 22523035
2005 PBK/TOPK, a proliferating neural progenitor-specific mitogen-activated protein kinase kinase. The Journal of neuroscience : the official journal of the Society for Neuroscience 93 16291951
2011 Coffee phenolic phytochemicals suppress colon cancer metastasis by targeting MEK and TOPK. Carcinogenesis 89 21317303
2004 Characterization of a MAPKK-like protein kinase TOPK. Biochemical and biophysical research communications 89 15541388
2015 Targeting PBK/TOPK decreases growth and survival of glioma initiating cells in vitro and attenuates tumor growth in vivo. Molecular cancer 82 26081429
2007 A mitotic kinase TOPK enhances Cdk1/cyclin B1-dependent phosphorylation of PRC1 and promotes cytokinesis. Journal of molecular biology 79 17512944
2019 PBK overexpression promotes metastasis of hepatocellular carcinoma via activating ETV4-uPAR signaling pathway. Cancer letters 77 30914208
2016 Overexpression of PBK/TOPK relates to tumour malignant potential and poor outcome of gastric carcinoma. British journal of cancer 75 27898655
2010 T-LAK cell-originated protein kinase (TOPK) phosphorylation of Prx1 at Ser-32 prevents UVB-induced apoptosis in RPMI7951 melanoma cells through the regulation of Prx1 peroxidase activity. The Journal of biological chemistry 69 20647304
2018 T-LAK cell-originated protein kinase (TOPK): an emerging target for cancer-specific therapeutics. Cell death & disease 68 30356039
2004 Pilot trial evaluating an 123I-labeled 80-kilodalton engineered anticarcinoembryonic antigen antibody fragment (cT84.66 minibody) in patients with colorectal cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 68 15297402
2019 PBK, targeted by EVI1, promotes metastasis and confers cisplatin resistance through inducing autophagy in high-grade serous ovarian carcinoma. Cell death & disease 57 30778048
2013 Combining in vitro embryotoxicity data with physiologically based kinetic (PBK) modelling to define in vivo dose-response curves for developmental toxicity of phenol in rat and human. Archives of toxicology 55 23943240
2015 PBK/TOPK enhances aggressive phenotype in prostate cancer via β-catenin-TCF/LEF-mediated matrix metalloproteinases production and invasion. Oncotarget 54 25909225
2021 PBK/TOPK: A Therapeutic Target Worthy of Attention. Cells 51 33670114
2021 The rice LEC1-like transcription factor OsNF-YB9 interacts with SPK, an endosperm-specific sucrose synthase protein kinase, and functions in seed development. The Plant journal : for cell and molecular biology 48 33721364
2010 Critical roles of LGN/GPSM2 phosphorylation by PBK/TOPK in cell division of breast cancer cells. Genes, chromosomes & cancer 48 20589935
2016 Oncogenic roles of TOPK and MELK, and effective growth suppression by small molecular inhibitors in kidney cancer cells. Oncotarget 45 26933922
2015 PBK/TOPK mediates geranylgeranylation signaling for breast cancer cell proliferation. Cancer cell international 45 25745361
2016 Overexpression of PBK/TOPK Contributes to Tumor Development and Poor Outcome of Esophageal Squamous Cell Carcinoma. Anticancer research 43 27919968
2012 c-Myc and E2F1 drive PBK/TOPK expression in high-grade malignant lymphomas. Leukemia research 43 23237560
2018 TOPK Promotes Microglia/Macrophage Polarization towards M2 Phenotype via Inhibition of HDAC1 and HDAC2 Activity after Transient Cerebral Ischemia. Aging and disease 42 29896413
2016 Integrating in vitro data and physiologically based kinetic (PBK) modelling to assess the in vivo potential developmental toxicity of a series of phenols. Archives of toxicology 41 27815601
2019 TOPK inhibits autophagy by phosphorylating ULK1 and promotes glioma resistance to TMZ. Cell death & disease 40 31378785
2005 Expression and phosphorylation of TOPK during spermatogenesis. Development, growth & differentiation 40 16316408
2021 PBK/TOPK: An Effective Drug Target with Diverse Therapeutic Potential. Cancers 38 34066486
2016 TOPK promotes lung cancer resistance to EGFR tyrosine kinase inhibitors by phosphorylating and activating c-Jun. Oncotarget 37 26745678
2018 Novel selective TOPK inhibitor SKLB-C05 inhibits colorectal carcinoma growth and metastasis. Cancer letters 36 30590102
2017 Role of TOPK in lipopolysaccharide-induced breast cancer cell migration and invasion. Oncotarget 36 28212583
2013 TOPK and PTEN participate in CHFR mediated mitotic checkpoint. Cellular signalling 36 24012691
2018 Cell growth inhibition by 3-deoxysappanchalcone is mediated by directly targeting the TOPK signaling pathway in colon cancer. Phytomedicine : international journal of phytotherapy and phytopharmacology 34 31035049
2016 Remote ischemic postconditioning protects against renal ischemia/reperfusion injury by activation of T-LAK-cell-originated protein kinase (TOPK)/PTEN/Akt signaling pathway mediated anti-oxidation and anti-inflammation. International immunopharmacology 34 27355132
2020 PBK promotes aggressive phenotypes of cervical cancer through ERK/c-Myc signaling pathway. Journal of cellular physiology 33 33184870
2015 PBK/TOPK mediates promyelocyte proliferation via Nrf2-regulated cell cycle progression and apoptosis. Oncology reports 33 26503118
2000 SPK-1, a C. elegans SR protein kinase homologue, is essential for embryogenesis and required for germline development. Mechanisms of development 33 11091073
2018 Targeting PRPK and TOPK for skin cancer prevention and therapy. Oncogene 32 29904102
2023 Identifying TOPK and Hypoxia Hallmarks in Esophageal Tumors for Photodynamic/Chemo/Immunotherapy and Liver Metastasis Inhibition with Nanocarriers. ACS nano 31 36853935
2017 TOPK (T-LAK cell-originated protein kinase) inhibitor exhibits growth suppressive effect on small cell lung cancer. Cancer science 31 28075524
2015 TOPK is highly expressed in circulating tumor cells, enabling metastasis of prostate cancer. Oncotarget 31 25881543
2014 Expression of PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) in human urinary bladder transitional cell carcinoma. Immunobiology 31 24629784
2017 ADA-07 Suppresses Solar Ultraviolet-Induced Skin Carcinogenesis by Directly Inhibiting TOPK. Molecular cancer therapeutics 29 28655782
2014 Activation of TOPK by lipopolysaccharide promotes induction of inducible nitric oxide synthase through NF-κB activity in leukemia cells. Cellular signalling 29 24440499
2019 MicroRNA-372 enhances radiosensitivity while inhibiting cell invasion and metastasis in nasopharyngeal carcinoma through activating the PBK-dependent p53 signaling pathway. Cancer medicine 28 30656832
2019 Targeting the COX2/MET/TOPK signaling axis induces apoptosis in gefitinib-resistant NSCLC cells. Cell death & disease 28 31611604
2017 CDK1-mediated mitotic phosphorylation of PBK is involved in cytokinesis and inhibits its oncogenic activity. Cellular signalling 28 28780319
2016 Phosphorylation of TOPK at Y74, Y272 by Src increases the stability of TOPK and promotes tumorigenesis of colon. Oncotarget 28 27016416
2015 Identification of the oncogenic kinase TOPK/PBK as a master mitotic regulator of C2H2 zinc finger proteins. Oncotarget 28 25575812
2021 PBK phosphorylates MSL1 to elicit epigenetic modulation of CD276 in nasopharyngeal carcinoma. Oncogenesis 27 33431797
2018 Mitotic kinase PBK/TOPK as a therapeutic target for adult T‑cell leukemia/lymphoma. International journal of oncology 27 29901068
2020 TOPK inhibition accelerates oxidative stress‑induced granulosa cell apoptosis via the p53/SIRT1 axis. International journal of molecular medicine 26 32901866
2016 The Protective Role of the TOPK/PBK Pathway in Myocardial Ischemia/Reperfusion and H₂O₂-Induced Injury in H9C2 Cardiomyocytes. International journal of molecular sciences 26 26907268
2020 PBK attenuates paclitaxel-induced autophagic cell death by suppressing p53 in H460 non-small-cell lung cancer cells. FEBS open bio 25 32237067
2019 TOPK promotes epithelial-mesenchymal transition and invasion of breast cancer cells through upregulation of TBX3 in TGF-β1/Smad signaling. Biochemical and biophysical research communications 25 31757421
2022 PBK drives PARP inhibitor resistance through the TRIM37/NFκB axis in ovarian cancer. Experimental & molecular medicine 24 35859118
2017 TOPK modulates tumour-specific radiosensitivity and correlates with recurrence after prostate radiotherapy. British journal of cancer 24 28677687
2016 PDZ binding kinase (PBK) is a theranostic target for nasopharyngeal carcinoma: driving tumor growth via ROS signaling and correlating with patient survival. Oncotarget 24 27049917
2021 Inactivation of TOPK Caused by Hyperglycemia Blocks Diabetic Heart Sensitivity to Sevoflurane Postconditioning by Impairing the PTEN/PI3K/Akt Signaling. Oxidative medicine and cellular longevity 23 33986917
2019 TOPK promotes metastasis of esophageal squamous cell carcinoma by activating the Src/GSK3β/STAT3 signaling pathway via γ-catenin. BMC cancer 21 31888532
2005 Efficacy and safety of tacrolimus compared with cyclosporin microemulsion in primary SPK transplantation: 3-year results of the Euro-SPK 001 trial. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 21 15814547
2023 FYN/TOPK/HSPB1 axis facilitates the proliferation and metastasis of gastric cancer. Journal of experimental & clinical cancer research : CR 20 37016377
2020 Activation of NF-κB by TOPK upregulates Snail/Slug expression in TGF-β1 signaling to induce epithelial-mesenchymal transition and invasion of breast cancer cells. Biochemical and biophysical research communications 20 32828273
2022 Down-regulation of PBK inhibits proliferation of human endometrial stromal cells in thin endometrium. Reproductive biology and endocrinology : RB&E 19 35105354
2022 TOPK/PBK is phosphorylated by ERK2 at serine 32, promotes tumorigenesis and is involved in sorafenib resistance in RCC. Cell death & disease 19 35546143
2021 PBK expression predicts favorable survival in colorectal cancer patients. Virchows Archiv : an international journal of pathology 19 33638656
2020 Suppression of the solar ultraviolet-induced skin carcinogenesis by TOPK inhibitor HI-TOPK-032. Oncogene 19 32277233
2018 Dual FLT3/TOPK inhibitor with activity against FLT3-ITD secondary mutations potently inhibits acute myeloid leukemia cell lines. Future medicinal chemistry 19 29437468
2017 Development of a Combined In Vitro Physiologically Based Kinetic (PBK) and Monte Carlo Modelling Approach to Predict Interindividual Human Variation in Phenol-Induced Developmental Toxicity. Toxicological sciences : an official journal of the Society of Toxicology 19 28498972
1999 RNA maturation of the rice SPK gene may involve trans-splicing. The Plant journal : for cell and molecular biology 19 10417713
2020 Targeting TOPK sensitises tumour cells to radiation-induced damage by enhancing replication stress. Cell death and differentiation 18 33168956
2021 PBK/TOPK promotes chemoresistance to oxaliplatin in hepatocellular carcinoma cells by regulating PTEN. Acta biochimica et biophysica Sinica 17 33772548
2021 Next generation risk assessment (NGRA): Bridging in vitro points-of-departure to human safety assessment using physiologically-based kinetic (PBK) modelling - A case study of doxorubicin with dose metrics considerations. Toxicology in vitro : an international journal published in association with BIBRA 17 33848589
2014 Expression of PBK/TOPK in cervical cancer and cervical intraepithelial neoplasia. International journal of clinical and experimental pathology 17 25550851
2018 Glycycoumarin Sensitizes Liver Cancer Cells to ABT-737 by Targeting De Novo Lipogenesis and TOPK-Survivin Axis. Nutrients 16 29543705
2018 Design, synthesis and biological evaluation of novel 1-phenyl phenanthridin-6(5H)-one derivatives as anti-tumor agents targeting TOPK. European journal of medicinal chemistry 16 30453248
2023 TOPK inhibits TNF-α-induced granulosa cell apoptosis via regulation of SIRT1/p53. Biochemical and biophysical research communications 15 37148702
2023 TOPK promotes the growth of esophageal cancer in vitro and in vivo by enhancing YB1/eEF1A1 signal pathway. Cell death & disease 15 37328464
2022 PBK Enhances Cellular Proliferation With Histone H3 Phosphorylation and Suppresses Migration and Invasion With CDH1 Stabilization in Colorectal Cancer. Frontiers in pharmacology 14 35115926
2019 Potent anti-myeloma activity of the TOPK inhibitor OTS514 in pre-clinical models. Cancer medicine 14 31714026
2017 Impact of a novel biomarker, T-LAK cell-originating protein kinase (TOPK) expression on outcome in malignant glioma. Neuropathology : official journal of the Japanese Society of Neuropathology 14 29271010
2012 In silico structural and functional analysis of the human TOPK protein by structure modeling and molecular dynamics studies. Journal of molecular modeling 14 22940854
2021 Menin-regulated Pbk controls high fat diet-induced compensatory beta cell proliferation. EMBO molecular medicine 13 33821572
2014 A physiologically based kinetic (PBK) model describing plasma concentrations of quercetin and its metabolites in rats. Biochemical pharmacology 13 24561179
2004 A rice antisense SPK transformant that lacks the accumulation of seed storage substances shows no correlation between sucrose concentration in phloem sap and demand for carbon sources in the sink organs. Plant & cell physiology 13 15356337
2022 PBK/TOPK inhibitor OTS964 resistance is mediated by ABCB1-dependent transport function in cancer: in vitro and in vivo study. Molecular cancer 12 35135547
2021 OTS964, a TOPK Inhibitor, Is Susceptible to ABCG2-Mediated Drug Resistance. Frontiers in pharmacology 12 33658942
2019 TOPK is regulated by PP2A and BCR/ABL in leukemia and enhances cell proliferation. International journal of oncology 12 30864683
2011 SPK-1, an SR protein kinase, inhibits programmed cell death in Caenorhabditis elegans. Proceedings of the National Academy of Sciences of the United States of America 12 21245325
2022 TOPK Affects Autophagy of Skin Squamous Cell Carcinoma by Regulating NF-KB Pathway through HDAC1. Disease markers 11 35756488
2023 The LIN28B-let-7-PBK pathway is essential for group 3 medulloblastoma tumor growth and survival. Molecular oncology 10 37341142
2021 An Integrative Pan-Cancer Analysis of PBK in Human Tumors. Frontiers in molecular biosciences 10 34859049
2020 TOPK mediates hypoxia-induced epithelial-mesenchymal transition and the invasion of nonsmall-cell lung cancer cells via the HIF-1α/snail axis. Biochemical and biophysical research communications 10 33158479
2019 [18F]FE-OTS964: a Small Molecule Targeting TOPK for In Vivo PET Imaging in a Glioblastoma Xenograft Model. Molecular imaging and biology 10 30357568
2019 Gossypetin Inhibits Solar-UV Induced Cutaneous Basal Cell Carcinoma Through Direct Inhibiting PBK/TOPK Protein Kinase. Anti-cancer agents in medicinal chemistry 10 30827262
2023 KRASG12C mutation-induced TOPK overexpression contributes to tumour progression in non-small cell lung cancer. Journal of cellular and molecular medicine 9 37226642