Affinage

PLK1

Serine/threonine-protein kinase PLK1 · UniProt P53350

Length
603 aa
Mass
68.3 kDa
Annotated
2026-04-28
100 papers in source corpus 43 papers cited in narrative 43 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PLK1 is a master mitotic serine/threonine kinase that orchestrates centrosome maturation, spindle assembly, kinetochore–microtubule attachment, chromosome integrity, cytokinesis, and centromeric CENP-A deposition through phosphorylation of a broad substrate repertoire. PLK1 activation requires Aurora-A–mediated phosphorylation of T210 in a process primed by CDK1-phosphorylated Bora/SPAT-1, and this activation operates as a bistable switch controlled by a dimerization-to-monomer transition that gates nuclear entry (PMID:25753036, PMID:34759346, PMID:24338364). At kinetochores, PLK1 is recruited via its polo-box domain (PBD) to CDK1/self-primed phosphodocking sites on BUB1, CENP-U, CLIP-170, and PBIP1, and is removed by non-proteolytic CUL3–KLHL22 ubiquitylation at K492; its kinase output is further tuned by SETD6 methylation (K209/K413), SET7/9 dimethylation (K191), PTEN-dependent dephosphorylation, and an Apolo1–PP1γ feedback loop (PMID:33248027, PMID:23455478, PMID:30622182, PMID:31863092, PMID:34260926). Beyond mitotic progression, PLK1 phosphorylates p53 and TAp63 to suppress apoptosis, phosphorylates Mre11 to terminate DNA-damage checkpoints, activates Polθ for mitotic DNA repair, restricts PrimPol chromatin loading to prevent replication-associated breaks, promotes CENP-A deposition by activating the Mis18 complex, and coordinates nuclear pore complex disassembly at mitotic entry (PMID:15024021, PMID:19668228, PMID:28512243, PMID:37674080, PMID:34860556, PMID:39236163, PMID:29487689).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1997 High

    Establishing PLK1 as a conserved cell-division kinase: mutagenesis of T210 and the catalytic domain demonstrated that PLK1 kinase activity is essential for viability and that T210 is a key activating residue, while yeast complementation proved functional conservation with Cdc5.

    Evidence Site-directed mutagenesis (K82M, D194N, T210D) with in vitro kinase assay and S. cerevisiae cdc5-1 complementation

    PMID:9154840

    Open questions at the time
    • Upstream activating kinase for T210 not yet identified
    • No structural information on the kinase domain available
  2. 2002 High

    Identifying the first mitotic substrate: PLK1 phosphorylation of TCTP attenuates its microtubule-stabilizing activity, providing direct evidence that PLK1 controls spindle microtubule dynamics through substrate phosphorylation.

    Evidence Two-hybrid screen; in vitro kinase assay; phospho-deficient TCTP mutant causes multinucleation phenocopying PLK1 loss

    PMID:12167714

    Open questions at the time
    • Specific TCTP phosphorylation sites not fully mapped
    • Relative contribution of TCTP versus other substrates to spindle assembly unclear
  3. 2003 High

    Demonstrating that PLK1 is essential for chromosome segregation and cell survival: PLK1 depletion causes mitotic arrest, failure of sister chromatid separation, DNA damage, and caspase-3-dependent apoptosis, establishing PLK1 as indispensable for mitotic fidelity.

    Evidence Vector-based siRNA with FACS, caspase-3 activation, and rescue by non-degradable PLK1

    PMID:12732729

    Open questions at the time
    • Direct substrates mediating sister chromatid separation not identified
    • Mechanism linking PLK1 loss to DNA damage not resolved
  4. 2004 High

    Revealing a reciprocal PLK1–p53 regulatory axis: PLK1 directly binds and phosphorylates p53 to inhibit its transcriptional and pro-apoptotic functions, while p53 reciprocally represses PLK1 transcription via direct promoter binding, establishing a feedback circuit that integrates mitotic signaling with tumor suppression.

    Evidence Co-IP with deletion mapping, kinase-dead mutant, luciferase reporter (2004); ChIP on PLK1 promoter with HDAC recruitment (2010)

    PMID:15024021 PMID:20962589

    Open questions at the time
    • Specific p53 phosphorylation sites by PLK1 not mapped
    • In vivo physiological significance of this feedback in normal tissues not established
  5. 2007 High

    Solving the structural basis for PLK1 kinase selectivity: crystal structures of the kinase domain with BI 2536 and with a DARPin chaperone revealed the active conformation and a Leu132-dependent selectivity pocket, enabling rational drug design.

    Evidence X-ray crystallography of PLK1 kinase domain with BI 2536 (2007) and DARPin 3H10 at 2.3 Å (2008)

    PMID:18005335 PMID:18391401

    Open questions at the time
    • Full-length PLK1 structure including PBD intramolecular contacts not determined
    • Structural basis of substrate recognition beyond PBD not resolved
  6. 2008 Medium

    Defining the self-priming mechanism for kinetochore recruitment: PLK1 phosphorylates PBIP1 to create its own PBD-docking site, then induces PBIP1 degradation to transition to other kinetochore receptors, establishing the principle that PLK1 generates and then consumes its own docking platforms.

    Evidence Cell-based localization with site-directed mutagenesis of PBIP1 phospho-epitope

    PMID:18215321

    Open questions at the time
    • Temporal order of receptor switching at kinetochores not fully resolved
    • Quantitative contribution of PBIP1 versus other docking sites unclear
  7. 2009 High

    Expanding PLK1's substrate repertoire to microtubule depolymerases: PLK1 phosphorylates Kif2a to enhance its depolymerase activity while Aurora-A antagonizes this, revealing a kinase-counterkinase mechanism controlling spindle microtubule length.

    Evidence Co-IP and in vitro kinase/depolymerase assay; PLK1 inhibition increases spindle microtubule intensity in vivo

    PMID:19351716

    Open questions at the time
    • Spatial coordination of PLK1 and Aurora-A on Kif2a at spindle poles not resolved
  8. 2012 High

    Demonstrating phospho-site-specific control of a kinesin: PLK1 phosphorylation of Kif2b at S204 governs kinetochore targeting while T125 phosphorylation activates error-correction function, showing that distinct phospho-events on a single substrate can control localization versus activity.

    Evidence Mass spectrometry phospho-mapping; in vitro kinase assay; phosphomutant localization and functional rescue

    PMID:22535524

    Open questions at the time
    • Whether PLK1-Kif2b axis acts independently of or redundantly with Aurora-B error correction not established
  9. 2013 High

    Discovering non-proteolytic ubiquitylation as a kinetochore removal mechanism: CUL3–KLHL22 ubiquitylates PLK1 at K492 within the PBD to dissociate it from kinetochores without degradation, revealing ubiquitin as a spatial regulator of PLK1 rather than a destruction signal.

    Evidence Mass spectrometry site identification; K492R mutant phenocopies KLHL22 depletion (sustained SAC activation)

    PMID:23455478

    Open questions at the time
    • Identity of deubiquitinase that reverses K492 modification unknown
    • Structural basis for how K492 ubiquitylation disrupts PBD binding not determined
  10. 2014 High

    Establishing a Cdk1→PLK1 sequential phosphorylation relay on procaspase-8 that suppresses extrinsic apoptosis during mitosis, integrating cell-cycle kinase signaling with death receptor signaling.

    Evidence In vitro kinase assay; PBD-docking site generated by Cdk1; S305A mutant sensitizes cells to Fas-induced apoptosis

    PMID:24484936

    Open questions at the time
    • Whether this mechanism operates in non-cancer cell contexts not tested
  11. 2015 High

    Resolving the activation cascade: CDK1 phosphorylates Bora/SPAT-1, which then stimulates Aurora-A–dependent T210 phosphorylation of PLK1, establishing the CDK1→Bora→Aurora-A→PLK1 mitotic entry relay as a conserved mechanism from C. elegans to humans.

    Evidence In vitro reconstitution of CDK1-Bora-Aurora A-PLK1 phosphorylation cascade; non-phosphorylatable SPAT-1 mutants in C. elegans embryos

    PMID:25753036

    Open questions at the time
    • Quantitative parameters of the bistable switch in vivo not measured
    • Spatial regulation of Bora–Aurora-A interaction at centrosomes not resolved
  12. 2016 High

    Revealing PBD dimerization as an autoinhibition-relief mechanism: crystal structure of Drosophila Polo PBD bound to phospho-Pon showed that two PBD molecules dimerize upon phosphopeptide binding, relieving intramolecular autoinhibition.

    Evidence Crystal structure of PBD/phospho-Pon complex; mutagenesis of dimer interface; in vitro kinase assay

    PMID:27238966

    Open questions at the time
    • Whether human PLK1 PBD dimerizes through the same interface not confirmed structurally
    • In vivo relevance of PBD dimerization for PLK1 regulation in mammalian cells not tested
  13. 2017 High

    Linking PLK1 to DNA-damage checkpoint termination: PLK1 phosphorylates Mre11 at S649, priming CK2 phosphorylation at S688 to inhibit MRN complex loading, providing a mechanism by which mitotic entry overrides DNA repair checkpoints.

    Evidence In vitro kinase assay; phosphomimetic/non-phosphorylatable Mre11 mutants; DNA damage focus assay; xenograft sensitivity

    PMID:28512243

    Open questions at the time
    • Whether PLK1-Mre11 regulation operates at all DSB types or only specific lesion classes unknown
  14. 2019 High

    Identifying lysine methylation as a negative regulatory mechanism: SETD6 methylates PLK1 at K209/K413 and SET7/9 dimethylates K191, each independently reducing PLK1 kinase activity; loss of these marks accelerates mitosis, establishing methylation as a kinase tuning mechanism complementary to phosphorylation and ubiquitylation.

    Evidence In vitro methyltransferase assays; non-methylatable PLK1 mutants with elevated activity; kinetochore-microtubule stability readout

    PMID:30622182 PMID:31863092

    Open questions at the time
    • Demethylases that reverse PLK1 methylation not identified
    • Structural mechanism by which methylation reduces ATP utilization unknown
  15. 2019 High

    Demonstrating PLK1's role in centromere structural integrity: PLK1 inactivation permits BLM helicase-dependent unwinding of centromeric DNA, which under bipolar tension leads to centromere rupture and chromosome arm splitting.

    Evidence PLK1 inhibitor with BLM depletion epistasis; live cell imaging of centromere decompaction

    PMID:31253795

    Open questions at the time
    • Direct PLK1 substrate at centromeres that restrains BLM not identified
    • Whether this mechanism operates in non-cancer cells unknown
  16. 2020 High

    Mapping the principal kinetochore docking receptors: BUB1 (outer) and CENP-U (inner) were identified as the main PLK1 receptors at kinetochores, each bearing paired PLK1-docking and PP2A-docking motifs created by CDK1/PLK1 priming phosphorylation, and promoting PLK1 dimerization at kinetochores.

    Evidence Ectopic localization assay; in vitro reconstitution; kinetochore PLK1 localization studies

    PMID:33248027

    Open questions at the time
    • Functional consequence of PLK1 dimerization at kinetochores versus monomeric activity not resolved
  17. 2021 High

    Revealing the dimer-to-monomer activation switch: PLK1 dimerizes in early G2 supported by Bora; Aurora-A–mediated T210 phosphorylation triggers dimer dissociation, generating monomers competent for importin binding and nuclear entry, thereby coupling activation to nuclear translocation.

    Evidence Biochemical dimerization assay; importin co-IP; nuclear localization assay with dimer-interface mutants

    PMID:34759346

    Open questions at the time
    • Structural basis of the PLK1 dimer interface in human PLK1 not determined
    • Whether dimer/monomer ratio is regulated by additional signals unknown
  18. 2021 High

    Discovering a self-limiting feedback loop at kinetochores: Apolo1 sustains PLK1 activity at kinetochores but, once phosphorylated by PLK1, recruits PP1γ to dephosphorylate and inactivate PLK1, constituting a substrate-mediated negative feedback timer.

    Evidence FRET-based PLK1 activity biosensor; co-IP; siRNA; phosphatase recruitment assay

    PMID:34260926

    Open questions at the time
    • Temporal resolution of Apolo1 phosphorylation relative to kinetochore–microtubule stabilization not established
  19. 2021 High

    Connecting PLK1 to genome protection during replication stress: PLK1 phosphorylates PrimPol between its RPA-binding motifs to prevent aberrant chromatin loading; reversal during replication stress licenses PrimPol access, and loss of this regulation causes chromosome breaks and micronuclei.

    Evidence In vitro kinase assay; chromatin recruitment assay; chromosome instability readouts

    PMID:34860556

    Open questions at the time
    • Phosphatase responsible for reversing PrimPol phosphorylation during stress not identified
  20. 2023 High

    Establishing PLK1 as the activating kinase for mitotic DNA repair via Polθ: PLK1 phosphorylates Polθ to activate it during mitosis, enabling TOPBP1-dependent recruitment to mitotic DSBs for end-joining; this pathway is essential for genome stability and is synthetically lethal with HR deficiency.

    Evidence In vitro kinase assay; Polθ–TOPBP1 direct interaction; KO phenotype; mitotic DNA repair assay; synthetic lethality with HR-deficient cells

    PMID:37674080

    Open questions at the time
    • Full spectrum of Polθ phosphorylation sites by PLK1 not mapped
    • Whether PLK1-Polθ axis operates outside mitosis unknown
  21. 2024 High

    Revealing PLK1's role in epigenetic centromere maintenance: PLK1 binds self-primed phosphorylations on Mis18α (S54) and Mis18BP1 (T78/S93) via its PBD, triggering a conformational change in the Mis18α–Mis18β complex that promotes HJURP recruitment and new CENP-A deposition in early G1, extending PLK1 function beyond mitosis into chromatin inheritance.

    Evidence Biochemical reconstitution; PBD binding assay; phospho-site mapping; CENP-A deposition assay (two independent groups)

    PMID:39236163 PMID:39236175

    Open questions at the time
    • How PLK1 activity persists into G1 after mitotic exit-associated degradation not explained
    • Whether PLK1-Mis18 regulation is perturbed in cancer aneuploidies unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Full-length PLK1 structure capturing the intramolecular PBD–kinase domain interface and its modulation by methylation, ubiquitylation, and dimerization remains undetermined; a unified quantitative model integrating all post-translational inputs (phosphorylation, methylation, ubiquitylation, dephosphorylation) into a spatiotemporal activity profile is lacking.
  • No full-length human PLK1 structure
  • No integrated quantitative model of combinatorial PTM regulation
  • Demethylases and deubiquitinases acting on PLK1 not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 13 GO:0016740 transferase activity 11
Localization
GO:0005694 chromosome 10 GO:0005815 microtubule organizing center 3 GO:0005634 nucleus 1
Pathway
R-HSA-1640170 Cell Cycle 9 R-HSA-162582 Signal Transduction 5 R-HSA-5357801 Programmed Cell Death 4 R-HSA-73894 DNA Repair 3 R-HSA-4839726 Chromatin organization 2
Partners
APOLO1AURKABORABUB1CENPUKLHL22MIS18ASETD6

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 PLK1 (Plk) is a functional homolog of S. cerevisiae Cdc5; Glu206 and Thr210 in the kinase domain are critical for catalytic activity, and replacement of Thr210 with a negatively charged residue (T210D) elevates Plk specific activity. Ectopic expression of Plk complements the cdc5-1 cell division defect in yeast in a kinase-activity-dependent manner. In vitro kinase assay with immunoprecipitates from Sf9 cells; site-directed mutagenesis (K82M, D194N, D194R, T210D); yeast complementation of cdc5-1 mutation Molecular and cellular biology High 9154840
2002 PLK1 phosphorylates the microtubule-stabilizing protein TCTP on two serine residues in vitro and in vivo; this phosphorylation decreases TCTP's microtubule-stabilizing activity, and overexpression of a phosphorylation-deficient TCTP mutant causes multinucleate cells and cell death similar to anti-Plk antibody microinjection phenotypes. Two-hybrid screen to identify Plk-interacting proteins; in vitro kinase assay; co-fractionation; in vivo phosphorylation analysis; overexpression of phosphomutant TCTP Molecular and cellular biology High 12167714
2003 Plk1 depletion in cancer cells causes mitotic arrest with 4N DNA content, formation of dumbbell-like chromatin structures (failure of sister chromatid separation), and apoptosis involving caspase-3 activation and p53 stabilization; DNA damage also occurs in p53-null cells. ATM inhibition potentiates lethality of Plk1 depletion. Vector-based siRNA depletion; FACS; caspase-3 activation assay; rescue with non-degradable Plk1 constructs; ATM inhibitor treatment Proceedings of the National Academy of Sciences of the United States of America High 12732729
2004 PLK1 physically binds to the DNA-binding region of p53 (identified by systematic immunoprecipitation with deletion mutants) and phosphorylates p53 in a kinase-dependent manner, thereby inhibiting p53 transcriptional activity and its pro-apoptotic function; a kinase-dead Plk1 mutant fails to suppress p53 activity. Co-immunoprecipitation with deletion mutants; confocal co-localization; luciferase reporter assay; kinase-dead mutant analysis The Journal of biological chemistry High 15024021
2005 PLK1's polo-box domain (PBD) interacts with MCM2 and MCM7 (and the whole MCM2-7 complex) in a chromatin-associated fraction, suggesting a role for PLK1 in coordinating DNA replication and mitotic events. PBD-based protein interaction screen; co-immunoprecipitation of endogenous proteins; immunoblot; chromatin fractionation The Journal of biological chemistry Medium 15654075
2007 Crystal structure of the PLK1 kinase domain in complex with the inhibitor BI 2536 reveals that Leu132 in the hinge region creates a small selectivity pocket exploited by BI 2536's methoxy group, providing structural basis for PLK1 selectivity over other kinases. X-ray crystallography (co-crystal structure of PLK1 kinase domain with BI 2536); selectivity profiling Chemical biology & drug design High 18005335
2008 Crystal structure of wild-type PLK1 kinase domain in complex with DARPin 3H10 solved at 2.3 Å, revealing the active conformation of PLK1 and enabling structure-based drug design. X-ray crystallography using DARPin as crystallization chaperone Acta crystallographica. Section D, Biological crystallography High 18391401
2008 PLK1 is recruited to centromeres through a self-priming mechanism: PLK1 phosphorylates the centromeric component PBIP1, generating its own PBD-binding site (phospho-epitope) for initial kinetochore recruitment; PLK1 subsequently induces PBIP1 delocalization and degradation to allow binding to other kinetochore components. Cell-based localization studies; biochemical analysis of PLK1-PBIP1 interaction; site-directed mutagenesis Cell division Medium 18215321
2008 In C. elegans embryos, PLK-1 is asymmetrically distributed between AB and P1 blastomeres under control of anterior-posterior PAR polarity cues, and this asymmetry promotes mitotic entry preferentially in AB; mild plk-1 RNAi delays mitosis specifically in P1 but not AB, independently of ATL-1/CHK-1. RNAi depletion in C. elegans; live imaging; genetic analysis with PAR mutants Development (Cambridge, England) High 18305005
2009 PLK1 interacts with the microtubule depolymerase Kif2a during mitosis in a kinase-activity-dependent manner and phosphorylates Kif2a to enhance its depolymerase activity in vitro; PLK1 inhibition decreases microtubule-associated Kif2a signals and increases spindle microtubule intensity in vivo. Aurora A antagonizes this by phosphorylating Kif2a to suppress its depolymerase activity. Proteomic identification; co-immunoprecipitation; in vitro kinase/depolymerase assay; PLK1 inhibition/depletion in vivo Journal of cell science High 19351716
2009 PLK1 phosphorylates TAp63 at Ser-52 of the TA domain (demonstrated by in vitro kinase assay), decreasing TAp63 protein stability and suppressing TAp63-induced apoptotic cell death in liver tumor cells; PLK1 binds p63 through its kinase domain via p63's DNA-binding region. Immunoprecipitation; in vitro pull-down; in vitro kinase assay; siRNA knockdown; double knockdown epistasis Oncogene High 19668228
2010 PICH (a PLK1-binding protein) and PLK1 kinase coordinately maintain chromosome arm architecture during prometaphase; PICH knockdown causes loss of PLK1 from chromosome arms, resulting in 'wavy' chromosome disorganization that can be prevented by topoisomerase II inhibition, suggesting the PICH-PLK1 complex normally acts via topoisomerase II activity. siRNA knockdown; live and fixed-cell imaging; chromosome architecture analysis; topoisomerase II inhibitor treatment Molecular biology of the cell Medium 20130082
2010 p53 represses PLK1 transcription directly: chromatin immunoprecipitation shows p53 binds two sites (p53RE1 and p53RE2) on the PLK1 promoter; DNA damage stimulates p53 recruitment to p53RE2 coincident with repression-associated chromatin changes including HDAC recruitment; this repression is independent of p21 and the CDE/CHR element. Chromatin immunoprecipitation (ChIP); reporter gene assay; siRNA; HDAC inhibitor treatment Cell cycle (Georgetown, Tex.) High 20962589
2012 PLK1 directly phosphorylates the kinesin-13 Kif2b at Thr125 and Ser204; phosphorylation of S204 is required for kinetochore localization of Kif2b in prometaphase, while T125 phosphorylation is required for Kif2b activity in correcting k-MT attachment errors. Mass spectrometry phospho-mapping; in vitro kinase assay; phosphomutant overexpression; kinetochore localization assay Molecular biology of the cell High 22535524
2013 The CUL3-KLHL22 E3 ubiquitin ligase ubiquitylates PLK1 at Lys492 within the PBD, causing PLK1 dissociation from kinetochore phosphoreceptors without proteolytic degradation; loss of KLHL22 causes PLK1 accumulation at kinetochores and sustained SAC activation; expression of non-ubiquitylatable PLK1-K492R phenocopies KLHL22 inactivation. Co-immunoprecipitation; mass spectrometry; siRNA; non-ubiquitylatable mutant expression; kinetochore localization; SAC analysis Nature cell biology High 23455478
2013 Bora-Aurora-A remains the major activating complex for PLK1 in mitosis (not only G2); a small amount of Aurora-A activity with residual Bora is sufficient to sustain PLK1 T210 phosphorylation in mitosis, creating a bistable switch where PLK1 is sensitive to Aurora-A inhibition during initial activation but refractory once fully activated. Kinase inhibitor treatment; immunoblotting of T210 phosphorylation; RNAi depletion of Bora Journal of cell science Medium 24338364
2014 Sequential phosphorylation of procaspase-8 by Cdk1/cyclin B1 at S387 (generating a PBD-docking phospho-epitope) followed by PLK1 at S305 suppresses extrinsic apoptosis during mitosis; non-phosphorylatable caspase-8 S305A increases Fas-stimulated cell death, and BI 2536 (PLK1 inhibitor) lowers the threshold for Fas-induced apoptosis. In vitro kinase assay; PBD-binding assay; RNAi replacement with phosphomutants; Fas-stimulation assay; BI 2536 treatment Molecular oncology High 24484936
2014 CLIP-170, phosphorylated by CDK1 at T287, acts as a PLK1 recruiter at kinetochores during early mitosis; depletion of CLIP-170 or expression of non-phosphorylatable CLIP-170-T287A reduces PLK1 kinetochore localization, destabilizes kinetochore fibers, and impairs chromosome alignment. Co-localization; siRNA depletion; phosphomutant expression; kinetochore fiber stability assay Journal of cell science High 24777477
2014 PLK1 regulates NEK2 activity, which in turn phosphorylates and stabilizes β-catenin at mitotic centrosomes; Plk1 inhibition or depletion disrupts this pathway. In vitro and cell-based assays show Nek2 phosphorylates β-catenin at N-terminal regulatory sites, blocking β-TrCP binding and preventing ubiquitination and degradation. In vitro kinase assay; co-immunoprecipitation; ubiquitination assay; PLK1 inhibitor treatment; siRNA Molecular biology of the cell High 24501426
2015 CDK-1 phosphorylates Bora/SPAT-1 at conserved Sp/Tp residues, promoting Bora interaction with PLK1 and stimulating Aurora A-dependent T-loop phosphorylation of PLK1 to trigger mitotic entry; phospho-SPAT-1 activates PLK1 by enabling Aurora A phosphorylation in vitro; this mechanism is conserved between C. elegans and humans. In vitro kinase assay (CDK1 phosphorylation of Bora; Aurora A phosphorylation of PLK1); non-phosphorylatable SPAT-1 mutant analysis in C. elegans embryos; human Bora/PLK1 reconstitution The Journal of cell biology High 25753036
2015 PLK1 is required for efficient meiotic resumption (nuclear envelope breakdown), recruitment of centrosomal proteins to acentriolar MTOCs, spindle formation, stable kinetochore-microtubule attachment, APC/C activation (by promoting EMI1 degradation), and chromosome condensation maintenance during meiosis I-II transition in mouse oocytes. Specific small-molecule PLK1 inhibition combined with live mouse oocyte imaging; time-lapse microscopy; APC/C activity assay PloS one High 25658810
2016 Drosophila Polo/PLK1's polo-box domain (PBD) binds phospho-Pon (phosphorylated by Cdk1 at Thr63), and crystal structure of Plk1 PBD/phospho-Pon complex reveals that two phospho-Pon-bound PBDs dimerize; this PBD dimerization relieves Plk1 autoinhibition and promotes sequential Plk1 phosphorylation of Pon. Crystal structure of PBD/phospho-Pon complex; in vitro binding assay; mutagenesis; in vitro kinase assay Structure (London, England : 1993) High 27238966
2016 PTEN physically associates with PLK1 and reduces PLK1 phosphorylation in a phosphatase-dependent manner; PTEN deficiency leads to elevated PLK1 phosphorylation; a phospho-mimetic PLK1 mutant causes polyploidy, and expression of non-phosphorylatable PLK1 or PLK1 inhibition reduces polyploid cell populations. Co-immunoprecipitation; phosphatase assay; phosphomimetic and non-phosphorylatable PLK1 mutant expression; ploidy analysis Cell cycle (Georgetown, Tex.) Medium 27398835
2017 PLK1 phosphorylates Mre11 at S649, priming subsequent CK2-mediated phosphorylation at S688; dual phosphorylation inhibits MRN complex loading onto damaged DNA, leading to premature DNA damage checkpoint termination and impaired DNA repair. In vitro kinase assay; phosphomimetic/non-phosphorylatable Mre11 mutants; DNA damage focus assay; checkpoint termination assay; xenograft tumor sensitivity assay Cancer research High 28512243
2017 PLK1 coordinates nuclear pore complex (NPC) disassembly at mitotic entry (but not lamin A/C disassembly) and negatively regulates NPC reassembly on lagging chromatin; this reveals independent regulatory pathways for lamin A/C (CDK1-dependent) and NPCs (PLK1-dependent) during mitosis. PLK1 inhibition; live cell imaging; immunofluorescence; functional analysis of NPC/lamin assembly on lagging chromatin Oncotarget Medium 29487689
2017 Plk1 phosphorylates Numb, leading to enhanced proteasomal degradation of Numb and impairment of the Numb/p53 pathway, thereby antagonizing p53 during DNA damage response; cancer cells expressing non-phosphorylatable Numb are more sensitive to doxorubicin. In vitro kinase assay; co-immunoprecipitation; proteasomal degradation assay; phosphomutant expression; xenograft model Oncogene High 29059161
2017 HMMR acts at centrosomes in a PLK1-dependent pathway that localizes active Ran and modulates cortical NuMA-dynein complexes for spindle orientation; HMMR loss causes spindle misorientation that phenocopies disruption of this PLK1-dependent pathway. Hmmr-knockout mouse model; live cell imaging; Ran-GTP localization; spindle orientation assay eLife Medium 28994651
2018 DNA replication restricts CDK1 and PLK1 activation; preventing DNA replication licensing or firing causes premature activation of CDK1 and PLK1 in S phase; in the presence of DNA replication, CHK1 and p38 inhibition also leads to premature mitotic kinase activation causing replication stress. Double-degron system for protein depletion; kinase inhibitors; cell cycle synchronization; kinase activity assays Molecular cell High 30008317
2018 PLK1 overexpression causes cytokinesis defects correlated with defective loading of Cep55 and ESCRT complexes to the abscission bridge in a PLK1 kinase-dependent manner, generating polyploid cells with reduced proliferative potential. Inducible knock-in mouse model; live cell imaging; Cep55/ESCRT localization assay; kinase-dead mutant Nature communications High 30069007
2019 SETD6 binds and methylates PLK1 at K209 and K413 during mitosis; lack of PLK1 methylation results in increased PLK1 kinase activity, accelerated mitosis, and faster cellular proliferation, revealing SETD6-mediated methylation as a negative regulator of PLK1 kinase activity. In vitro methyltransferase assay; SETD6-deficient cells; non-methylatable PLK1 mutants; kinase activity assay; time-lapse microscopy Proceedings of the National Academy of Sciences of the United States of America High 30622182
2019 PLK1 inhibition reveals a centromere disintegration mechanism: PLK1 inactivation allows BLM helicase to unwind DNA at a specific centromere domain, and under bipolar spindle pulling, the distorted centromeres are decompacted into threadlike DNA molecules leading to centromere rupture and chromosome arm splitting. PLK1 small-molecule inhibition; live cell imaging; BLM depletion epistasis; centromere structure analysis Nature communications High 31253795
2020 BUB1 (outer kinetochore) and CENP-U (inner kinetochore) are the main PLK1 receptors at kinetochores; both share a constellation of sequence motifs (PP2A-docking motif and two PLK1-docking sites); PLK1 recruitment requires priming phosphorylation by CDK1 and PLK1 itself, and promotes PLK1 dimerization. Ectopic localization assay; in vitro reconstitution; kinetochore localization studies; biochemical binding assays Molecular cell High 33248027
2020 BRCA2 is phosphorylated by PLK1 at T207 (a bona fide PLK1 docking site); BRCA2 bound to PLK1 forms a complex with PP2A and phospho-BUBR1; disruption of BRCA2-PLK1 binding (BRCA2 variants S206C and T207A) destabilizes this complex, causing unstable kinetochore-microtubule interactions, chromosome misalignment, and aneuploidy. Phosphorylation site mapping; co-immunoprecipitation; BRCA2 variant analysis; kinetochore-microtubule stability assay; chromosome alignment analysis Nature communications High 32286328
2020 SET7/9 dimethylates PLK1 at Lys191 at kinetochores during early mitosis, tuning down PLK1 kinase activity by limiting ATP utilization; overexpression of non-methylatable PLK1 or SET7/9 inhibition causes mitotic arrest due to destabilized kinetochore-microtubule attachments. In vitro methyltransferase assay; non-methylatable PLK1 mutant expression; PLK1 kinase activity assay; kinetochore-microtubule stability analysis; SET7/9 inhibitor treatment Journal of molecular cell biology High 31863092
2021 PLK1 dimerization during early G2 phase (supported by Bora) fine-tunes PLK1 activation timing and nuclear entry; T210 phosphorylation by Aurora-A triggers dimer dissociation generating active PLK1 monomers; interfering with this dimer/monomer switch prevents importin association and nuclear PLK1 localization during G2-M transition. Biochemical dimerization assay; T210 phosphorylation analysis; importin co-immunoprecipitation; nuclear localization assay; dimer interface mutants Oncogene High 34759346
2021 Apolo1 localizes to kinetochores during early mitosis, sustains PLK1 kinase activity at kinetochores for accurate kinetochore-microtubule attachment, and is itself a PLK1 substrate; PLK1-phosphorylated Apolo1 recruits PP1γ to dephosphorylate and inactivate PLK1, constituting a feedback loop that fine-tunes PLK1 activity. FRET-based PLK1 activity biosensor; co-immunoprecipitation; siRNA; kinase assay; phosphatase recruitment assay Cell reports High 34260926
2021 PLK1 activity is essential for time-dependent release of 53BP1 from kinetochores (through CENP-F as docking partner); PLK1 inhibition causes 53BP1 persistence at kinetochores, preventing cytosolic 53BP1 association with p53 and blunting the mitotic surveillance pathway (mitotic stopwatch). PLK1 inhibitor treatment; 53BP1 localization imaging; CENP-F-53BP1 binding disruption; mitotic surveillance pathway activation assay EMBO reports High 37888778
2021 PLK1 regulates PrimPol by phosphorylating it at a conserved residue between its RPA binding motifs, preventing aberrant PrimPol chromatin recruitment; this phosphorylation is cell cycle regulated and reversed during replication stress; loss of PLK1-dependent PrimPol regulation causes chromosome breaks and micronuclei. In vitro kinase assay; chromatin recruitment assay; cell cycle phosphorylation analysis; chromosome instability readouts (breaks, micronuclei); drug sensitivity assays Science advances High 34860556
2021 PLK1 promotes NLRP3 inflammasome activation at cell interphase; a proximity-dependent BioID screen identifies enhanced PLK1-NLRP3 proximity upon inflammasome activation; PLK1 orchestrates MTOC structure and NLRP3 subcellular positioning upon inflammasome activation; PLK1 inhibition suppresses IL-1β production in vivo. BioID proximity screen; co-immunoprecipitation (interaction domain mapping); PLK1 inhibitor in vivo; NLRP3 subcellular localization; MTOC organization assay The Journal of clinical investigation Medium 37698938
2023 PLK1 phosphorylates DNA polymerase theta (Polθ) to activate it specifically during mitosis; phosphorylated Polθ is recruited via direct interaction with BRCA1 C-terminal domains of TOPBP1 to mitotic DNA double-strand breaks, where it mediates DNA end joining; loss of Polθ leads to defective mitotic DSB repair and genome instability. In vitro kinase assay; direct protein interaction assay (Polθ-TOPBP1); KO phenotype analysis; DNA repair assay in mitosis; synthetic lethality assay with HR-deficient cells Nature High 37674080
2023 PLK1 maintains intralysosomal pH by regulating ATP6V1A phosphorylation, and PLK1 inhibition impairs lysosomal function leading to blockade of autophagic flux and reduced fibroblast activation in renal fibrosis. PLK1 pharmacological inhibition/genetic KO; lysosomal pH measurement; autophagic flux assay; ATP6V1A phosphorylation analysis; UUO mouse model Cell death & disease Medium 37640723
2024 PLK1 promotes CENP-A deposition in early G1 by interacting with the Mis18 complex through recognition of self-primed phosphorylations on Mis18α (Ser54) and Mis18BP1 (Thr78 and Ser93) via its polo-box domain; PLK1 binding activates a conformational switch in Mis18α-Mis18β and promotes Mis18 complex-HJURP interaction required for CENP-A loading. Biochemical reconstitution; PLK1 PBD binding assay; phosphorylation site mapping; structural analysis; functional CENP-A deposition assay Science (New York, N.Y.) High 39236163
2024 PLK1 interacts with Mis18α and Mis18BP1 through their self-primed phosphorylations (Mis18α Ser54, Mis18BP1 Thr78 and Ser93) recognized by PLK1's polo-box domain; disrupting these phosphorylations perturbs HJURP centromere recruitment and new CENP-A loading; PLK1 binding activates Mis18α-Mis18β complex. Biochemical and functional analysis of Mis18 phosphorylation; PLK1 PBD-binding assay; HJURP recruitment assay; CENP-A loading assay Science (New York, N.Y.) High 39236175

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Polo-like kinase (Plk)1 depletion induces apoptosis in cancer cells. Proceedings of the National Academy of Sciences of the United States of America 432 12732729
2008 Polo on the Rise-from Mitotic Entry to Cytokinesis with Plk1. Developmental cell 425 18477449
2004 Polo-like kinase 1 (Plk1) inhibits p53 function by physical interaction and phosphorylation. The Journal of biological chemistry 227 15024021
2002 Plk phosphorylation regulates the microtubule-stabilizing protein TCTP. Molecular and cellular biology 224 12167714
2009 Polo-like kinase (PLK) inhibitors in preclinical and early clinical development in oncology. The oncologist 206 19474163
2005 Intravesical administration of small interfering RNA targeting PLK-1 successfully prevents the growth of bladder cancer. The Journal of clinical investigation 169 15761500
1997 Plk is a functional homolog of Saccharomyces cerevisiae Cdc5, and elevated Plk activity induces multiple septation structures. Molecular and cellular biology 165 9154840
2021 Polo-like kinase 1 (PLK1) signaling in cancer and beyond. Biochemical pharmacology 154 34454931
2018 Plk1 overexpression induces chromosomal instability and suppresses tumor development. Nature communications 133 30069007
2017 Playing polo during mitosis: PLK1 takes the lead. Oncogene 131 28436952
1997 Cell cycle regulation of the human polo-like kinase (PLK) promoter. The Journal of biological chemistry 118 9083047
2005 Silencing of polo-like kinase (Plk) 1 via siRNA causes induction of apoptosis and impairment of mitosis machinery in human prostate cancer cells: implications for the treatment of prostate cancer. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 117 15661849
2001 Comparative expression of the mitotic regulators SAK and PLK in colorectal cancer. Annals of surgical oncology 105 11597015
2015 Recent Advances and New Strategies in Targeting Plk1 for Anticancer Therapy. Trends in pharmacological sciences 103 26478211
2010 p53-dependent repression of polo-like kinase-1 (PLK1). Cell cycle (Georgetown, Tex.) 102 20962589
2013 Ubiquitylation-dependent localization of PLK1 in mitosis. Nature cell biology 100 23455478
2018 DNA Replication Determines Timing of Mitosis by Restricting CDK1 and PLK1 Activation. Molecular cell 99 30008317
2023 Polθ is phosphorylated by PLK1 to repair double-strand breaks in mitosis. Nature 98 37674080
2007 Selectivity-determining residues in Plk1. Chemical biology & drug design 98 18005335
2022 Present and Future Perspective on PLK1 Inhibition in Cancer Treatment. Frontiers in oncology 93 35719948
2014 Molecular dynamics of PLK1 during mitosis. Molecular & cellular oncology 92 27308323
2013 Bora and Aurora-A continue to activate Plk1 in mitosis. Journal of cell science 91 24338364
2016 Spotlight on Volasertib: Preclinical and Clinical Evaluation of a Promising Plk1 Inhibitor. Medicinal research reviews 89 27140825
2020 BUB1 and CENP-U, Primed by CDK1, Are the Main PLK1 Kinetochore Receptors in Mitosis. Molecular cell 88 33248027
2018 Regulating a key mitotic regulator, polo-like kinase 1 (PLK1). Cytoskeleton (Hoboken, N.J.) 88 30414309
2009 Plk1 and Aurora A regulate the depolymerase activity and the cellular localization of Kif2a. Journal of cell science 85 19351716
2015 Multiple requirements of PLK1 during mouse oocyte maturation. PloS one 83 25658810
2014 Nek2 phosphorylates and stabilizes β-catenin at mitotic centrosomes downstream of Plk1. Molecular biology of the cell 82 24501426
2015 Cross-Talk between AURKA and Plk1 in Mitotic Entry and Spindle Assembly. Frontiers in oncology 81 26779436
2006 Overexpression of polo-like kinase 1 (PLK1) and chromosomal instability in bladder cancer. Oncology 78 16837776
2018 MiR-126 negatively regulates PLK-4 to impact the development of hepatocellular carcinoma via ATR/CHEK1 pathway. Cell death & disease 74 30315225
2008 PLK-1 asymmetry contributes to asynchronous cell division of C. elegans embryos. Development (Cambridge, England) 74 18305005
2001 Polo-like kinase (PLK) expression in endometrial carcinoma. Cancer letters 71 11410324
2014 Sequential Cdk1 and Plk1 phosphorylation of caspase-8 triggers apoptotic cell death during mitosis. Molecular oncology 63 24484936
2023 Multiple Roles of PLK1 in Mitosis and Meiosis. Cells 60 36611980
2017 Plk1 Phosphorylation of Mre11 Antagonizes the DNA Damage Response. Cancer research 53 28512243
2008 Silencing of polo-like kinase (Plk) 1 via siRNA causes inhibition of growth and induction of apoptosis in human esophageal cancer cells. Oncology 53 18714168
2015 Cdk1 phosphorylates SPAT-1/Bora to trigger PLK-1 activation and drive mitotic entry in C. elegans embryos. The Journal of cell biology 51 25753036
2012 Plk1 regulates the kinesin-13 protein Kif2b to promote faithful chromosome segregation. Molecular biology of the cell 50 22535524
2017 HMMR acts in the PLK1-dependent spindle positioning pathway and supports neural development. eLife 49 28994651
2010 The substrates of Plk1, beyond the functions in mitosis. Protein & cell 49 21153517
2020 Proper chromosome alignment depends on BRCA2 phosphorylation by PLK1. Nature communications 48 32286328
2016 PLK-1: Angel or devil for cell cycle progression. Biochimica et biophysica acta 47 26899266
2023 CCNE1 and PLK1 Mediate Resistance to Palbociclib in HR+/HER2- Metastatic Breast Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 46 36749874
2005 Interaction of chromatin-associated Plk1 and Mcm7. The Journal of biological chemistry 45 15654075
2015 PLK-1 Targeted Inhibitors and Their Potential against Tumorigenesis. BioMed research international 42 26557691
2014 Plk1-targeted therapies in TP53- or RAS-mutated cancer. Mutation research. Reviews in mutation research 38 24630986
2015 Caenorhabditis elegans polo-like kinase PLK-1 is required for merging parental genomes into a single nucleus. Molecular biology of the cell 37 26490119
2010 PICH and cotargeted Plk1 coordinately maintain prometaphase chromosome arm architecture. Molecular biology of the cell 37 20130082
2008 Structure of wild-type Plk-1 kinase domain in complex with a selective DARPin. Acta crystallographica. Section D, Biological crystallography 37 18391401
2005 Expression of Polo-Like Kinase (PLK1) in non-Hodgkin's lymphomas. Leukemia & lymphoma 37 15621805
2019 Polo-like kinase 1 (Plk1) inhibition synergizes with taxanes in triple negative breast cancer. PloS one 36 31751384
2022 A novel PLK1 inhibitor onvansertib effectively sensitizes MYC-driven medulloblastoma to radiotherapy. Neuro-oncology 35 34477871
2016 PTEN regulates PLK1 and controls chromosomal stability during cell division. Cell cycle (Georgetown, Tex.) 35 27398835
2019 The methyltransferase SETD6 regulates Mitotic progression through PLK1 methylation. Proceedings of the National Academy of Sciences of the United States of America 34 30622182
2017 CDK1 and PLK1 coordinate the disassembly and reassembly of the nuclear envelope in vertebrate mitosis. Oncotarget 34 29487689
2016 Mitotic entry: The interplay between Cdk1, Plk1 and Bora. Cell cycle (Georgetown, Tex.) 33 27831827
2008 Self-regulated mechanism of Plk1 localization to kinetochores: lessons from the Plk1-PBIP1 interaction. Cell division 32 18215321
2020 PLK1 is required for chromosome compaction and microtubule organization in mouse oocytes. Molecular biology of the cell 30 32267211
2019 PLK1 facilitates chromosome biorientation by suppressing centromere disintegration driven by BLM-mediated unwinding and spindle pulling. Nature communications 30 31253795
2019 Complex karyotype AML displays G2/M signature and hypersensitivity to PLK1 inhibition. Blood advances 29 30782614
2014 CLIP-170 recruits PLK1 to kinetochores during early mitosis for chromosome alignment. Journal of cell science 29 24777477
2004 Polo-like kinase (Plk) 1: a novel target for the treatment of prostate cancer. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 29 14718382
2024 Role of protein kinase PLK1 in the epigenetic maintenance of centromeres. Science (New York, N.Y.) 28 39236163
2021 PLK1 regulates centrosome migration and spindle dynamics in male mouse meiosis. EMBO reports 28 33615693
2021 Luteolin-Fabricated ZnO Nanostructures Showed PLK-1 Mediated Anti-Breast Cancer Activity. Biomolecules 28 33807771
2012 Systematic analysis of the Plk-mediated phosphoregulation in eukaryotes. Briefings in bioinformatics 27 22851512
2021 Overlapping roles for PLK1 and Aurora A during meiotic centrosome biogenesis in mouse spermatocytes. EMBO reports 25 33615678
2021 PLK1 Inhibition Induces Immunogenic Cell Death and Enhances Immunity against NSCLC. International journal of medical sciences 25 34522178
2020 Dual PLK1 and STAT3 inhibition promotes glioblastoma cells apoptosis through MYC. Biochemical and biophysical research communications 25 32962858
2007 TTDN1 is a Plk1-interacting protein involved in maintenance of cell cycle integrity. Cellular and molecular life sciences : CMLS 25 17310276
2017 Polo-like kinase 1 (Plk1) overexpression enhances ionizing radiation-induced cancer formation in mice. The Journal of biological chemistry 24 28900036
2012 Superiority of PLK-2 as α-synuclein phosphorylating agent relies on unique specificity determinants. Biochemical and biophysical research communications 24 22248692
2009 Plk1 regulates liver tumor cell death by phosphorylation of TAp63. Oncogene 24 19668228
2003 Cell cycle dependent expression of Plk1 in synchronized porcine fetal fibroblasts. Molecular reproduction and development 24 12784245
2024 PLK1-mediated phosphorylation cascade activates Mis18 complex to ensure centromere inheritance. Science (New York, N.Y.) 23 39236175
2021 Feedback control of PLK1 by Apolo1 ensures accurate chromosome segregation. Cell reports 23 34260926
2020 Methylation of PLK1 by SET7/9 ensures accurate kinetochore-microtubule dynamics. Journal of molecular cell biology 23 31863092
2020 PLK1- and PLK4-Mediated Asymmetric Mitotic Centrosome Size and Positioning in the Early Zebrafish Embryo. Current biology : CB 23 32916112
2019 Synergistic activity of BET inhibitor MK-8628 and PLK inhibitor Volasertib in preclinical models of medulloblastoma. Cancer letters 23 30611741
2018 Hsa-let-7b inhibits cell proliferation by targeting PLK1 in HCC. Gene 23 29913237
2013 TrkC promotes survival and growth of leukemia cells through Akt-mTOR-dependent up-regulation of PLK-1 and Twist-1. Molecules and cells 23 23832765
2010 BI_2536--targeting the mitotic kinase Polo-like kinase 1 (Plk1). Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer 23 20072841
2020 Combination of Inhibitors of USP7 and PLK1 has a Strong Synergism against Paclitaxel Resistance. International journal of molecular sciences 22 33207738
2016 Phospho-Pon Binding-Mediated Fine-Tuning of Plk1 Activity. Structure (London, England : 1993) 21 27238966
2021 A dimerization-dependent mechanism regulates enzymatic activation and nuclear entry of PLK1. Oncogene 20 34759346
2023 Plk1 promotes renal tubulointerstitial fibrosis by targeting autophagy/lysosome axis. Cell death & disease 19 37640723
2023 Chronic chromosome instability induced by Plk1 results in immune suppression in breast cancer. Cell reports 19 37979172
2014 Liver kinase B1 regulates the centrosome via PLK1. Cell death & disease 19 24722282
2013 CUL3 and protein kinases: insights from PLK1/KLHL22 interaction. Cell cycle (Georgetown, Tex.) 19 24067371
2005 Polo-like kinase (Plk) 1 as a target for prostate cancer management. IUBMB life 19 16223707
2021 PLK1 regulates the PrimPol damage tolerance pathway during the cell cycle. Science advances 18 34860556
2019 LSD1 Inhibition Attenuates Tumor Growth by Disrupting PLK1 Mitotic Pathway. Molecular cancer research : MCR 18 30760542
2019 PLK1 targets NOTCH1 during DNA damage and mitotic progression. The Journal of biological chemistry 18 31597699
2017 Plk1 phosphorylation of Numb leads to impaired DNA damage response. Oncogene 18 29059161
2023 PLK1 inhibition dampens NLRP3 inflammasome-elicited response in inflammatory disease models. The Journal of clinical investigation 17 37698938
2023 PLK1 promotes the mitotic surveillance pathway by controlling cytosolic 53BP1 availability. EMBO reports 17 37888778
2020 SKA3 Promotes Cell Growth in Breast Cancer by Inhibiting PLK-1 Protein Degradation. Technology in cancer research & treatment 16 32799774
2017 Gravin regulates centrosome function through PLK1. Molecular biology of the cell 16 29282278
2018 miR‑23a suppresses pancreatic cancer cell progression by inhibiting PLK‑1 expression. Molecular medicine reports 15 29749476