Affinage

PBK

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

Length
322 aa
Mass
36.1 kDa
Annotated
2026-06-10
100 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PBK/TOPK is a MAPKK-like serine/threonine kinase that couples mitotic cell-cycle signaling to chromatin dynamics, cytokinesis, and oncogenic survival pathways (PMID:15541388, PMID:28780319). During mitosis it is activated by CDK1/cyclin B phosphorylation at Thr-9 (and additional sites Thr-24, Ser-32, Ser-59), whereupon it associates with the mitotic spindle and is required for spindle midzone formation and cytokinesis (PMID:15541388, PMID:28780319); mechanistically it complexes with CDK1/cyclin B1 and PRC1 on microtubules to enhance PRC1 phosphorylation (PMID:17512944), phosphorylates LGN/GPSM2 at Thr450 to ensure faithful chromosome segregation (PMID:20589935), directly phosphorylates Histone H3 (PMID:35115926), and serves as the master kinase that phosphorylates the conserved linker of C2H2 zinc-finger proteins to drive their global dissociation from condensing chromatin (PMID:25575812). Beyond mitosis, TOPK functions as a node in stress and survival signaling: it phosphorylates the peroxiredoxin Prx1 (Ser-32) to enhance peroxidase activity and block UVB-induced apoptosis (PMID:20647304), stabilizes the p38-specific phosphatase MKP1 to restrain p38 and inflammation in vivo (PMID:21715333), and binds and suppresses p53 transactivation to license checkpoint bypass (PMID:20622899). In cancer, TOPK is a hub that drives proliferation, invasion, and therapy resistance through substrates including c-Jun (Ser63/Ser73, activating AP-1) (PMID:32277233), ULK1 (Ser469/Ser495/Ser533, inhibiting autophagy) (PMID:31378785), and HSPB1 (PMID:37016377), and its kinase activity is itself amplified by upstream tyrosine kinases Src, JAK2, MET, and FYN that phosphorylate Tyr74/Tyr272 to stabilize the protein and enhance its catalytic output (PMID:27016416, PMID:35780928, PMID:37016377). Pharmacologic TOPK inhibition phenocopies knockdown, producing cytokinesis failure and cancer-cell apoptosis (PMID:25338756). PBK expression is transcriptionally controlled by E2F/CREB, c-Myc–E2F1, EVI1, and a menin/JunD/HDAC3 repressor complex (PMID:16171862, PMID:33821572), and the protein is degraded via CHFR-mediated ubiquitination and dephosphorylated by PP2A (PMID:24012691, PMID:30864683).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2004 High

    Established TOPK as a mitotic effector by showing CDK1/cyclin B phosphorylates it at Thr-9 to target it to the spindle and drive cytokinesis, defining its core cell-cycle function.

    Evidence Immunofluorescence, kinase assay, and siRNA knockdown with cytokinesis readout

    PMID:15541388

    Open questions at the time
    • Did not identify the spindle substrates downstream of TOPK
    • Activation mechanism beyond Thr-9 not resolved
  2. 2005 Medium

    Connected TOPK to p38 MAPK signaling and to transcriptional control, showing it phosphorylates p38 in cycling progenitors and that its own expression is driven by E2F and CREB/ATF.

    Evidence In vitro kinase assay, cell-cycle synchronization, transgenic ablation; EMSA and reporter assays for promoter elements

    PMID:16171862 PMID:16291951

    Open questions at the time
    • Direct vs indirect p38 phosphorylation not fully separated
    • Promoter regulation tested in limited cell contexts
  3. 2007 High

    Defined the molecular partner and substrate of TOPK in cytokinesis, showing it complexes with CDK1/cyclin B1 and PRC1 and enhances PRC1 phosphorylation, and revealed a reciprocal feedback loop with ERK2.

    Evidence Reciprocal Co-IP, in vitro kinase assay, in vivo phosphorylation, knockdown/rescue

    PMID:17512944 PMID:17631144

    Open questions at the time
    • Feedback loop with ERK2 from single lab
    • Stoichiometry of the CDK1/PRC1/TOPK complex not quantified
  4. 2010 High

    Expanded the TOPK substrate repertoire to chromosome segregation and redox/checkpoint control, identifying LGN/GPSM2-Thr450, Prx1-Ser32, and p53 binding as functional targets.

    Evidence In vitro kinase assays with defined phosphosites, CD spectroscopy, Co-IP/yeast two-hybrid, microarray with knockdown

    PMID:20589935 PMID:20622899 PMID:20647304

    Open questions at the time
    • p53 interaction is binding-based suppression, not catalytic
    • In vivo relevance of Prx1-Ser32 across tissues unaddressed
  5. 2011 High

    Provided in vivo proof of TOPK's role in restraining inflammation by showing it phosphorylates and stabilizes MKP1 to dampen p38, with TOPK-knockout mice displaying UV-induced skin inflammation.

    Evidence In vitro kinase assay and TOPK knockout mouse with inflammation phenotype

    PMID:21715333

    Open questions at the time
    • MKP1 phosphosite mapping not detailed
    • Reconciliation with TOPK-as-p38-activator findings unresolved
  6. 2015 Medium

    Identified TOPK as the master mitotic kinase for C2H2 zinc-finger linker regions, mechanistically linking it to global chromatin dissociation during mitosis, and demonstrated that kinase inhibition (OTS964) is sufficient to block cytokinesis therapeutically.

    Evidence Inhibitor panel and affinity purification with kinase validation; siRNA/inhibitor comparison with xenograft models

    PMID:25338756 PMID:25575812

    Open questions at the time
    • ZFP linker phosphorylation shown globally but few individual ZFPs validated
    • Off-target profile of OTS964 not fully excluded
  7. 2016 Medium

    Established upstream tyrosine-kinase regulation of TOPK, showing Src phosphorylates Tyr74/Tyr272 to stabilize TOPK and enhance activity, and linked TOPK to TKI resistance via c-Jun/AP-1.

    Evidence In vitro kinase assays, phospho-specific antibodies, Src-knockout MEFs, pulse-chase; Co-IP and reporter assays for c-Jun axis

    PMID:26745678 PMID:27016416

    Open questions at the time
    • Relative contribution of each Tyr site to stability vs activity not dissected
    • c-Jun phosphosites defined in a later study
  8. 2017 High

    Clarified the regulatory logic of mitotic phosphorylation, mapping CDK1 sites (Thr9/Thr24/Ser32/Ser59) and showing the non-phosphorylatable T9A mutant is more oncogenic, indicating mitotic phosphorylation inhibits TOPK's transforming activity.

    Evidence In vitro kinase assay, phosphosite mutagenesis, soft-agar and cytokinesis assays

    PMID:28780319

    Open questions at the time
    • Mechanism by which Thr9 phosphorylation suppresses oncogenic output unresolved
    • Interplay with tyrosine phosphorylation not examined
  9. 2019 Medium

    Broadened TOPK's signaling reach to autophagy, transcription, and metastasis, identifying ULK1, YB1, and ETV4/uPAR axes and additional upstream inputs (MET, EVI1, PRPK, CHFR/PP2A regulation).

    Evidence Co-IP, in vitro kinase assays with defined phosphosites, ChIP, autophagy flux assays, xenograft and knockout models

    PMID:29904102 PMID:30778048 PMID:30864683 PMID:30914208 PMID:31378785 PMID:31611604 PMID:31888532 PMID:37328464

    Open questions at the time
    • Many substrate/axis findings from single labs in specific cancer contexts
    • Hierarchy among the many parallel oncogenic outputs unclear
  10. 2020 High

    Established a JNK-independent route to AP-1 activation and a role in replication-stress checkpoint signaling, showing TOPK directly phosphorylates c-Jun Ser63/Ser73 and interacts with CHK1/Cdc25c to protect stalled forks.

    Evidence In vitro kinase assay with phosphosites, AP-1 reporter, in vivo carcinogenesis model; Co-IP, DNA fiber and ssDNA foci assays

    PMID:32277233 PMID:33168956

    Open questions at the time
    • Whether CHK1/Cdc25c are TOPK substrates not established
    • Coordination of mitotic vs S-phase roles unaddressed
  11. 2021 Medium

    Connected TOPK to chromatin-acetylation machinery and refined its transcriptional repression, showing it phosphorylates MSL1 to promote MSL-complex/H4K16ac at CD276, while a menin/JunD/HDAC3 complex epigenetically represses Pbk in beta cells.

    Evidence Co-IP, kinase assay, ChIP, histone acetylation assay; ChIP and kinase-dead knock-in mouse with metabolic readout

    PMID:33431797 PMID:33821572

    Open questions at the time
    • MSL1 phosphosite not mapped in detail
    • Generality of menin/JunD repression beyond beta cells untested
  12. 2022 Medium

    Consolidated the upstream tyrosine-kinase network and direct substrate set, confirming JAK2-Tyr74 stabilization, ERK2-Ser32 as a resistance site, TRIM37 phosphorylation, and direct Histone H3 phosphorylation by recombinant PBK.

    Evidence Co-IP, in vitro reconstitution kinase assays, phospho-specific antibodies, xenograft models

    PMID:35115926 PMID:35546143 PMID:35780928 PMID:35859118

    Open questions at the time
    • Redundancy/specificity among Src, JAK2, MET, FYN inputs unresolved
    • CDH1 shown to be phosphorylated only indirectly
  13. 2023 High

    Defined a complete tyrosine-kinase-to-substrate cascade, showing FYN phosphorylates TOPK at Tyr272 and TOPK in turn phosphorylates HSPB1-Ser15 to drive gastric cancer, validated with knockout mice and phosphoproteomics.

    Evidence Co-IP, radioisotope and in vitro kinase assays, phosphoproteomics, TOPK knockout mice

    PMID:37016377

    Open questions at the time
    • Tissue specificity of FYN-TOPK-HSPB1 vs other tyrosine-kinase inputs unclear
    • HSPB1-Ser15 downstream effectors not fully mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TOPK's many parallel substrate axes are prioritized and coordinated in space and time — reconciling its mitotic chromatin/cytokinesis roles with its diverse interphase oncogenic and stress-survival outputs — remains unresolved.
  • No integrated model ranking substrates by context
  • Structural basis of dual Ser/Thr and Tyr-regulated activation not defined
  • In vivo substrate hierarchy in normal vs tumor tissue unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 9 GO:0016740 transferase activity 4 GO:0140110 transcription regulator activity 3
Localization
GO:0005634 nucleus 3 GO:0005856 cytoskeleton 2
Pathway
R-HSA-1640170 Cell Cycle 5 R-HSA-162582 Signal Transduction 4 R-HSA-4839726 Chromatin organization 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-9612973 Autophagy 2
Partners
CCNB1CDK1CHFRFYNJAK2PRC1SRCTP53

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 TOPK is phosphorylated at Thr-9 by CDK1/cyclin B during mitosis, causing TOPK to associate with mitotic spindles; suppression of TOPK expression 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 forms a complex with CDK1/cyclin B1 and PRC1 on microtubules during mitosis; TOPK enhances CDK1/cyclin B1-dependent phosphorylation of PRC1 at T481 (requiring both TOPK enzymatic activity and physical association with PRC1), thereby promoting cytokinesis. Co-immunoprecipitation, in vitro kinase assay, in vivo phosphorylation analysis, functional overexpression/knockdown Journal of molecular biology High 17512944
2007 TOPK and ERK2 form a positive feedback loop: TOPK phosphorylates ERK2 and ERK2 phosphorylates TOPK; EGF-stimulated knockdown of either reduces phosphorylation of the other and blocks downstream ERK2 substrate phosphorylation. In vitro kinase assay, siRNA knockdown, transient transfection, Western blot in HCT116 cells Gastroenterology Medium 17631144
2006 PBK/TOPK is necessary for appropriate p38 MAPK activation by growth factors; PBK knockdown impairs p38 activation, reduces cell motility, and results in an impaired DNA damage response (decreased γ-H2AX generation, increased DNA damage). siRNA knockdown, Western blot, clonogenic assay, motility assay Oncogene Medium 17160018
2005 PBK/TOPK phosphorylates p38 MAPK and is activated in a cell-cycle-dependent manner in neural progenitor cells; inhibition of this pathway disrupts progenitor proliferation and self-renewal. In vitro kinase assay, cell-cycle synchronization, transgenic ablation with lineage tracing in mice The Journal of neuroscience Medium 16291951
2005 TOPK-Thr-9 is specifically phosphorylated by CDK1/cyclin B during both mitotic and meiotic phases in spermatogenic cells, implicating TOPK in cytokinesis and/or chromosomal segregation during spermatogenesis. Immunohistochemistry, Western blot with phospho-specific antibodies on testis sections Development, growth & differentiation Medium 16316408
2010 TOPK physically interacts with the DNA-binding domain of p53 (including five common point mutants); PBK/TOPK knockdown upregulates p53 target genes (p21, apoptotic genes) particularly after genotoxic damage, indicating PBK suppresses p53 transactivation function. Co-immunoprecipitation, yeast two-hybrid, gene microarray, siRNA knockdown with qPCR/Western blot readouts in HCT116 and MCF-7 cells Oncogene High 20622899
2007 PBK physically interacts with p53 (detected by Co-IP and yeast two-hybrid) and downregulates p53, enabling cells to bypass DNA damage checkpoint; a phosphomimetic PBK mutant promotes polyploidization and aberrant mitotic entry after doxorubicin treatment. Co-immunoprecipitation, yeast two-hybrid, ectopic overexpression with flow cytometry (MPM-2 marker) Biochemical and biophysical research communications Medium 17482142
2010 TOPK binds Prx1 and phosphorylates it at Ser-32; this phosphorylation alters the secondary structure of Prx1 and enhances its peroxidase activity, blocking UVB-induced H2O2 accumulation and apoptosis in melanoma cells. LC-MS/MS pulldown identification, in vitro kinase assay, CD spectroscopy of Prx1/S32A mutant, flow cytometry, stable siRNA knockdown The Journal of biological chemistry High 20647304
2011 TOPK negatively regulates p38α activity by phosphorylating the p38α-specific phosphatase MKP1 and enhancing MKP1 stability; TOPK-knockout mice display markedly increased skin inflammation after solar UV irradiation. In vitro kinase assay, Western blot, TOPK knockout mouse model with inflammation phenotype The Journal of biological chemistry High 21715333
2010 PBK/TOPK phosphorylates LGN/GPSM2 at Thr450 during mitosis; overexpression of non-phosphorylatable LGN/GPSM2-T450A causes aberrant chromosomal segregation and growth suppression in breast cancer cells. In vitro kinase assay, Western blot with phospho-specific analysis, siRNA knockdown, mutant overexpression with phenotypic readout Genes, chromosomes & cancer High 20589935
2013 TOPK/PBK is ubiquitinated and targeted for degradation by the E3 ubiquitin ligase CHFR; TOPK in turn phosphorylates and inactivates PTEN, which activates Akt, facilitating G2/M progression in a CHFR-mediated mitotic checkpoint pathway. Co-immunoprecipitation, ubiquitination assay, in vitro kinase assay, siRNA knockdown with cell-cycle readout Cellular signalling Medium 24012691
2016 Src directly binds and phosphorylates TOPK at Tyr74 and Tyr272; these phosphorylations increase TOPK stability by inhibiting its ubiquitination and enhance TOPK kinase activity (measured by Histone H3-Ser10 phosphorylation); TOPK-Y74F/Y272F double mutant displays reduced tumorigenic activity. In vitro kinase assay with recombinant proteins, phospho-specific antibody generation, stable transfection with mutants, Co-IP, pulse-chase protein stability assay, Src-knockout MEFs Oncotarget High 27016416
2017 CDK1 phosphorylates PBK at Thr-9 (and also Thr-24, Ser-32, Ser-59) during mitosis; Thr-9 phosphorylation is required for normal cytokinesis; non-phosphorylatable PBK-T9A augments tumorigenesis more than wild-type PBK, indicating mitotic phosphorylation inhibits PBK's oncogenic activity. In vitro kinase assay, phospho-site mutagenesis, stable cell lines, soft agar assay, immunofluorescence cytokinesis analysis Cellular signalling High 28780319
2015 TOPK/PBK is the master kinase responsible for phosphorylating the conserved linker region of C2H2 zinc finger proteins (ZFPs) during mitosis, causing their dissociation from condensing chromatin; TOPK is activated by CDK1 and acts as the global ZFP linker kinase. Kinase inhibitor panel screen, biotinylated K252a affinity purification, in vitro kinase assay, in vivo phosphorylation correlation Oncotarget Medium 25575812
2014 TOPK inhibition with OTS964 causes cytokinesis defects and subsequent apoptosis of cancer cells, similar to siRNA knockdown; TOPK kinase inhibition (not just expression loss) is sufficient to block cytokinesis. In vitro kinase assay, siRNA comparison, xenograft tumor models, liposomal drug formulation Science translational medicine High 25338756
2016 TOPK promotes lung cancer resistance to EGFR-TKIs by directly binding and phosphorylating c-Jun, which activates AP-1 target genes CCND1 and CDC2; TOPK silencing sensitizes TKI-resistant cells to gefitinib. Co-immunoprecipitation, in vitro kinase assay, luciferase reporter, siRNA knockdown with drug-sensitivity assay, xenograft model Oncotarget Medium 26745678
2019 MET phosphorylates TOPK at Tyr74, preventing apoptosis in gefitinib-resistant NSCLC cells; this is part of the COX2-TXA2-MET-TOPK axis. Western blot with phospho-specific antibodies, in vitro signaling analysis, inhibitor combination studies in vitro and in vivo Cell death & disease Medium 31611604
2019 TOPK directly binds and phosphorylates ULK1 at Ser469, Ser495, and Ser533, decreasing ULK1 activity and stability and thereby inhibiting autophagy initiation in glioma cells. Co-immunoprecipitation, in vitro kinase assay with identified phosphosites, Western blot, autophagy flux assay Cell death & disease High 31378785
2018 TOPK promotes microglia/macrophage M2 polarization by binding to HDAC1 and HDAC2 and promoting their phosphorylation, inhibiting their deacetylase activity; this contributes to neuroprotection after cerebral ischemia. Co-immunoprecipitation (in vivo binding), in vitro TOPK overexpression in BV2 cells, immunofluorescence co-localization, Western blot Aging and disease Medium 29896413
2014 TOPK activates NF-κB by interacting with and phosphorylating IκBα in response to LPS, promoting iNOS transcription and nitric oxide production in leukemia cells. Co-immunoprecipitation, in vitro kinase assay against IκBα, NF-κB/iNOS promoter-driven luciferase assay, siRNA knockdown Cellular signalling Medium 24440499
2019 PBK promotes HCC metastasis via the ETV4-uPAR signaling pathway: PBK enhances binding of ETV4 to the uPAR promoter (shown by ChIP assay), activating uPAR transcription; uPAR overexpression rescues PBK-knockdown metastatic phenotype in vivo. ChIP assay, promoter reporter assay, gain/loss-of-function in vitro migration/invasion, orthotopic mouse model Cancer letters Medium 30914208
2021 PBK phosphorylates MSL1, enhancing MSL1 interaction with MSL2, MSL3, and KAT8 (MSL complex components), promoting MSL complex enrichment on the CD276 promoter, increasing histone H4 K16 acetylation and CD276 transcription in nasopharyngeal carcinoma. Co-immunoprecipitation, in vitro kinase assay, ChIP assay, histone acetylation assay Oncogenesis Medium 33431797
2022 PBK directly interacts with TRIM37 and promotes its phosphorylation and nuclear translocation, activating the NFκB pathway and conferring PARPi resistance in ovarian cancer. Co-immunoprecipitation, Western blot for nuclear translocation, NF-κB pathway analysis, in vitro and in vivo drug resistance assays Experimental & molecular medicine Medium 35859118
2022 ERK2 phosphorylates TOPK at Ser32 (a novel site beyond the previously known Thr9), and p-TOPK(S32) contributes to sorafenib resistance in renal cell carcinoma; HGF/c-MET signaling activates p-TOPK(S32) during resistance. Phospho-specific antibody, Western blot, in vitro kinase assay, combination inhibitor studies Cell death & disease Medium 35546143
2022 JAK2 directly binds and phosphorylates TOPK at Tyr74; this phosphorylation stabilizes TOPK and enhances phosphorylation of Histone H3 (a TOPK substrate) in Burkitt lymphoma cells, promoting tumor growth. Co-immunoprecipitation, in vitro kinase assay, in vivo/in vitro Histone H3 phosphorylation assay, xenograft model Cancer letters Medium 35780928
2023 FYN (a non-receptor tyrosine kinase) directly binds TOPK and phosphorylates it at Tyr272; TOPK in turn phosphorylates HSPB1 at Ser15; the FYN-TOPK-HSPB1 cascade drives gastric cancer proliferation and metastasis. Co-IP, pulldown assay, 32P-labeled isotope radioautography kinase assay, in vitro kinase assay, phospho-specific antibodies, phosphoproteomics, TOPK knockout mice Journal of experimental & clinical cancer research High 37016377
2019 TOPK promotes esophageal cancer through phosphorylation of YB1 at Thr89 and Ser209; phosphorylated YB1 binds the eEF1A1 promoter to activate its transcription, subsequently activating AKT/mTOR signaling. In vitro kinase assay with defined phosphosites, ChIP assay, Western blot, TOPK knockout with rescue, xenograft model Cell death & disease Medium 37328464
2019 TOPK is regulated by the E3 ubiquitin ligase/checkpoint protein CHFR (ubiquitination-mediated degradation); PP2A dephosphorylates TOPK (okadaic acid increases TOPK phosphorylation; FTY720/PP2A activator decreases it); BCR/ABL upregulates TOPK expression. Western blot with PP2A activator/inhibitor, BCR/ABL overexpression/imatinib inhibition, co-culture assays International journal of oncology Medium 30864683
2015 PBK/TOPK promotes geranylgeranylation-dependent breast cancer proliferation through YAP; YAP mediates geranylgeranylation-regulated PBK expression, placing PBK downstream of the Hippo-YAP signaling pathway. shRNA knockdown of YAP, HMG-CoA reductase inhibitor and GGTI-298 treatment, Western blot, proliferation assay Cancer cell international Low 25745361
2018 TOPK is identified as a substrate of PRPK; TOPK phosphorylates PRPK, and knockdown of TOPK inhibits PRPK phosphorylation and reduces solar-simulated light-induced skin carcinogenesis in mouse models. In vivo/ex vivo phosphorylation analysis, TOPK knockdown in mouse skin cancer model, topical inhibitor treatment with carcinogenesis readout Oncogene Medium 29904102
2020 TOPK directly binds and phosphorylates c-Jun at Ser63 and Ser73 after SSL (solar-simulated light) exposure in a JNK-independent manner, activating AP-1 transcriptional activity and promoting skin carcinogenesis. In vitro kinase assay, Co-IP, Western blot with phospho-specific antibodies, AP-1 luciferase reporter, siRNA knockdown, in vivo mouse carcinogenesis model Oncogene High 32277233
2005 PBK transcription is regulated by E2F (at -146 bp) and CREB/ATF (at -312 bp) binding sites in the PBK promoter; knockdown of these transcription factors decreases PBK protein expression, and PBK is downregulated during doxorubicin-induced growth arrest. EMSA, siRNA knockdown of transcription factors, luciferase reporter assay Leukemia research Medium 16171862
2012 c-Myc regulates PBK expression through E2F1; c-Myc–E2F1–PBK constitutes a signaling pathway in high-grade lymphomas, and inhibition of c-Myc, E2F1, or PBK comparably decreases cell growth and survival. siRNA knockdown of c-Myc and E2F1 with PBK protein/mRNA readout, correlation analysis, cell viability assay Leukemia research Low 23237560
2021 Menin and HDAC3 are recruited by JunD to the Pbk promoter, reducing histone H3 acetylation and epigenetically repressing Pbk expression; menin inhibitor disrupts menin-JunD interaction and augments Pbk transcription, promoting beta cell proliferation in a Pbk-kinase-dependent manner. ChIP assay, Pbk kinase-dead knock-in mouse, menin inhibitor treatment, glucose tolerance assay EMBO molecular medicine High 33821572
2020 TOPK interacts directly with CHK1 and Cdc25c; TOPK depletion increases replication fork stalling and collapse under replication stress, impairs recovery from fork stalling, and increases replication-associated ssDNA foci, revealing a role for TOPK in S-phase checkpoint signaling. Co-immunoprecipitation, DNA fiber assay, immunofluorescence for ssDNA foci, siRNA knockdown, xenograft model Cell death and differentiation Medium 33168956
2022 PBK directly phosphorylates histone H3 (confirmed by in vitro kinase assay with recombinant PBK and H3); PBK failed to directly phosphorylate CDH1 in vitro, though it promotes CDH1 phosphorylation indirectly in cells. In vitro kinase assay with recombinant proteins, Western blot in colorectal cancer cells Frontiers in pharmacology Medium 35115926
2019 EVI1 (ecotropic viral integration site-1) transcription factor directly targets the PBK promoter region and regulates PBK expression, placing PBK downstream of EVI1 in ovarian cancer; PBK promotes autophagy and cisplatin resistance via the ERK/mTOR signaling pathway. ChIP/promoter assay, ERK/mTOR Western blot, autophagy inhibitor rescue, in vivo xenograft Cell death & disease Medium 30778048
2019 TOPK promotes invasion of ESCC cells by activating the Src/GSK3β/STAT3 and ERK signaling pathways via γ-catenin, identified by protein kinase array and mass spectrometry. Protein kinase array, mass spectrometry, immunofluorescence, Western blot, in vitro invasion assay, lung metastasis mouse model BMC cancer Medium 31888532

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 130 17631144
2006 PBK/TOPK promotes tumour cell proliferation through p38 MAPK activity and regulation of the DNA damage response. Oncogene 125 17160018
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
2014 TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibition of cytokinesis. Science translational medicine 110 25338756
2010 PBK/TOPK interacts with the DBD domain of tumor suppressor p53 and modulates expression of transcriptional targets including p21. Oncogene 104 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 102 11783945
2012 Novel TOPK inhibitor HI-TOPK-032 effectively suppresses colon cancer growth. Cancer research 95 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 94 16291951
2004 Characterization of a MAPKK-like protein kinase TOPK. Biochemical and biophysical research communications 90 15541388
2011 Coffee phenolic phytochemicals suppress colon cancer metastasis by targeting MEK and TOPK. Carcinogenesis 89 21317303
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 78 30914208
2016 Overexpression of PBK/TOPK relates to tumour malignant potential and poor outcome of gastric carcinoma. British journal of cancer 76 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 71 20647304
2018 T-LAK cell-originated protein kinase (TOPK): an emerging target for cancer-specific therapeutics. Cell death & disease 70 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 69 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
2015 PBK/TOPK enhances aggressive phenotype in prostate cancer via β-catenin-TCF/LEF-mediated matrix metalloproteinases production and invasion. Oncotarget 56 25909225
2021 PBK/TOPK: A Therapeutic Target Worthy of Attention. Cells 51 33670114
2010 Critical roles of LGN/GPSM2 phosphorylation by PBK/TOPK in cell division of breast cancer cells. Genes, chromosomes & cancer 48 20589935
2015 PBK/TOPK mediates geranylgeranylation signaling for breast cancer cell proliferation. Cancer cell international 46 25745361
2011 T-LAK cell-originated protein kinase (TOPK) phosphorylation of MKP1 protein prevents solar ultraviolet light-induced inflammation through inhibition of the p38 protein signaling pathway. The Journal of biological chemistry 46 21715333
2016 Oncogenic roles of TOPK and MELK, and effective growth suppression by small molecular inhibitors in kidney cancer cells. Oncotarget 45 26933922
2016 Overexpression of PBK/TOPK Contributes to Tumor Development and Poor Outcome of Esophageal Squamous Cell Carcinoma. Anticancer research 45 27919968
2012 c-Myc and E2F1 drive PBK/TOPK expression in high-grade malignant lymphomas. Leukemia research 43 23237560
2007 Attenuation of DNA damage checkpoint by PBK, a novel mitotic kinase, involves protein-protein interaction with tumor suppressor p53. Biochemical and biophysical research communications 43 17482142
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
2019 TOPK inhibits autophagy by phosphorylating ULK1 and promotes glioma resistance to TMZ. Cell death & disease 41 31378785
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
2005 Expression and phosphorylation of TOPK during spermatogenesis. Development, growth & differentiation 41 16316408
2021 PBK/TOPK: An Effective Drug Target with Diverse Therapeutic Potential. Cancers 40 34066486
2016 TOPK promotes lung cancer resistance to EGFR tyrosine kinase inhibitors by phosphorylating and activating c-Jun. Oncotarget 39 26745678
2018 Novel selective TOPK inhibitor SKLB-C05 inhibits colorectal carcinoma growth and metastasis. Cancer letters 37 30590102
2017 Role of TOPK in lipopolysaccharide-induced breast cancer cell migration and invasion. Oncotarget 37 28212583
2013 TOPK and PTEN participate in CHFR mediated mitotic checkpoint. Cellular signalling 37 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 36 31035049
2023 Identifying TOPK and Hypoxia Hallmarks in Esophageal Tumors for Photodynamic/Chemo/Immunotherapy and Liver Metastasis Inhibition with Nanocarriers. ACS nano 34 36853935
2020 PBK promotes aggressive phenotypes of cervical cancer through ERK/c-Myc signaling pathway. Journal of cellular physiology 34 33184870
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
2015 PBK/TOPK mediates promyelocyte proliferation via Nrf2-regulated cell cycle progression and apoptosis. Oncology reports 34 26503118
2018 Targeting PRPK and TOPK for skin cancer prevention and therapy. Oncogene 33 29904102
2017 TOPK (T-LAK cell-originated protein kinase) inhibitor exhibits growth suppressive effect on small cell lung cancer. Cancer science 32 28075524
2015 TOPK is highly expressed in circulating tumor cells, enabling metastasis of prostate cancer. Oncotarget 31 25881543
2014 Activation of TOPK by lipopolysaccharide promotes induction of inducible nitric oxide synthase through NF-κB activity in leukemia cells. Cellular signalling 31 24440499
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 30 28655782
2005 Expression of PDZ-binding kinase (PBK) is regulated by cell cycle-specific transcription factors E2F and CREB/ATF. Leukemia research 30 16171862
2019 Targeting the COX2/MET/TOPK signaling axis induces apoptosis in gefitinib-resistant NSCLC cells. Cell death & disease 29 31611604
2016 Phosphorylation of TOPK at Y74, Y272 by Src increases the stability of TOPK and promotes tumorigenesis of colon. Oncotarget 29 27016416
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
2017 CDK1-mediated mitotic phosphorylation of PBK is involved in cytokinesis and inhibits its oncogenic activity. Cellular signalling 28 28780319
2015 Identification of the oncogenic kinase TOPK/PBK as a master mitotic regulator of C2H2 zinc finger proteins. Oncotarget 28 25575812
2013 Expression profiling of 519 kinase genes in matched malignant peripheral nerve sheath tumor/plexiform neurofibroma samples is discriminatory and identifies mitotic regulators BUB1B, PBK and NEK2 as overexpressed with transformation. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 28 23370767
2022 PBK drives PARP inhibitor resistance through the TRIM37/NFκB axis in ovarian cancer. Experimental & molecular medicine 27 35859118
2021 PBK phosphorylates MSL1 to elicit epigenetic modulation of CD276 in nasopharyngeal carcinoma. Oncogenesis 27 33431797
2020 TOPK inhibition accelerates oxidative stress‑induced granulosa cell apoptosis via the p53/SIRT1 axis. International journal of molecular medicine 27 32901866
2018 Mitotic kinase PBK/TOPK as a therapeutic target for adult T‑cell leukemia/lymphoma. International journal of oncology 27 29901068
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 26 31757421
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
2017 TOPK modulates tumour-specific radiosensitivity and correlates with recurrence after prostate radiotherapy. British journal of cancer 25 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 25 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 24 33986917
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 23 32828273
2019 TOPK promotes metastasis of esophageal squamous cell carcinoma by activating the Src/GSK3β/STAT3 signaling pathway via γ-catenin. BMC cancer 22 31888532
2023 FYN/TOPK/HSPB1 axis facilitates the proliferation and metastasis of gastric cancer. Journal of experimental & clinical cancer research : CR 21 37016377
2022 TOPK/PBK is phosphorylated by ERK2 at serine 32, promotes tumorigenesis and is involved in sorafenib resistance in RCC. Cell death & disease 20 35546143
2021 PBK expression predicts favorable survival in colorectal cancer patients. Virchows Archiv : an international journal of pathology 20 33638656
2020 Suppression of the solar ultraviolet-induced skin carcinogenesis by TOPK inhibitor HI-TOPK-032. Oncogene 20 32277233
2020 Targeting TOPK sensitises tumour cells to radiation-induced damage by enhancing replication stress. Cell death and differentiation 20 33168956
2022 Down-regulation of PBK inhibits proliferation of human endometrial stromal cells in thin endometrium. Reproductive biology and endocrinology : RB&E 19 35105354
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
2021 PBK/TOPK promotes chemoresistance to oxaliplatin in hepatocellular carcinoma cells by regulating PTEN. Acta biochimica et biophysica Sinica 18 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 18 33848589
2023 TOPK inhibits TNF-α-induced granulosa cell apoptosis via regulation of SIRT1/p53. Biochemical and biophysical research communications 17 37148702
2023 TOPK promotes the growth of esophageal cancer in vitro and in vivo by enhancing YB1/eEF1A1 signal pathway. Cell death & disease 17 37328464
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 17 30453248
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
2012 In silico structural and functional analysis of the human TOPK protein by structure modeling and molecular dynamics studies. Journal of molecular modeling 15 22940854
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
2022 PBK/TOPK inhibitor OTS964 resistance is mediated by ABCB1-dependent transport function in cancer: in vitro and in vivo study. Molecular cancer 14 35135547
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
2022 TOPK Affects Autophagy of Skin Squamous Cell Carcinoma by Regulating NF-KB Pathway through HDAC1. Disease markers 13 35756488
2021 OTS964, a TOPK Inhibitor, Is Susceptible to ABCG2-Mediated Drug Resistance. Frontiers in pharmacology 13 33658942
2021 Menin-regulated Pbk controls high fat diet-induced compensatory beta cell proliferation. EMBO molecular medicine 13 33821572
2021 Targeting Feedforward Loops Formed by Nuclear Receptor RORγ and Kinase PBK in mCRPC with Hyperactive AR Signaling. Cancers 13 33916325
2019 TOPK is regulated by PP2A and BCR/ABL in leukemia and enhances cell proliferation. International journal of oncology 13 30864683
2014 A physiologically based kinetic (PBK) model describing plasma concentrations of quercetin and its metabolites in rats. Biochemical pharmacology 13 24561179
2024 The TOPK Inhibitor HI-TOPK-032 Enhances CAR T-cell Therapy of Hepatocellular Carcinoma by Upregulating Memory T Cells. Cancer immunology research 11 38407902
2023 The LIN28B-let-7-PBK pathway is essential for group 3 medulloblastoma tumor growth and survival. Molecular oncology 11 37341142
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 11 33158479
2024 The oncogenic kinase TOPK upregulates in psoriatic keratinocytes and contributes to psoriasis progression by regulating neutrophils infiltration. Cell communication and signaling : CCS 10 39090602
2021 An Integrative Pan-Cancer Analysis of PBK in Human Tumors. Frontiers in molecular biosciences 10 34859049
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
2022 Phosphorylation of PBK/TOPK Tyr74 by JAK2 promotes Burkitt lymphoma tumor growth. Cancer letters 9 35780928

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