| 1994 |
Human PLK (PLK1) encodes a serine/threonine kinase of 603 amino acids; its mRNA expression is strongly correlated with mitotic activity of cells, being absent in resting cells and induced upon cell cycle entry. |
cDNA cloning, Northern blot analysis, cell synchronization experiments |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
8127874
|
| 1997 |
The PLK1 promoter contains a repressor element (CDE/CHR) near the transcription start site that mediates cell cycle-dependent transcription; three activating regions are located between −35 and −93 bp upstream, with promoter activity maximal at G2/M phase. |
PLK promoter/luciferase constructs in synchronized HeLa cells, deletion/mutation analysis |
The Journal of biological chemistry |
Medium |
9083047
|
| 2000 |
PLK1 binds to and phosphorylates the Golgi peripheral protein GRASP65 in vitro and in vivo; deletion or frameshift mutations in the conserved C-terminal polo-box domain of PLK1 greatly diminish its ability to phosphorylate GRASP65, demonstrating the PBD is required for this substrate interaction. |
Yeast two-hybrid screen, co-immunoprecipitation, in vitro kinase assay, deletion/frameshift mutant analysis |
Proceedings of the National Academy of Sciences of the United States of America |
High |
11050165
|
| 2000 |
The Ste20-like kinase SLK can phosphorylate and activate murine PLK1; SLK activity increases during G2 phase progression, proposing SLK as an upstream kinase regulating PLK1 in the somatic cell cycle. |
In vitro kinase assay, endogenous SLK activity measurements, cell synchronization |
Genes to cells : devoted to molecular & cellular mechanisms |
Medium |
10886374
|
| 2003 |
Depletion of PLK1 by siRNA causes cell cycle arrest with 4N DNA content, formation of dumbbell-like chromatin, activation of caspase-3, and apoptosis; the p53 pathway and ATM are involved in PLK1-depletion-induced apoptosis, and DNA damage occurs even in p53-null cells. |
Vector-based siRNA knockdown, FACS, caspase-3 activation assay, rescue with non-degradable Plk1, ATM inhibitor co-treatment |
Proceedings of the National Academy of Sciences of the United States of America |
High |
12732729
|
| 2003 |
BRCA1 mediates repression of PLK1 mRNA after ionizing radiation through a CHK1-dependent pathway, and loss of BRCA1 impairs this downregulation, linking BRCA1 to G2/M checkpoint control via PLK1 transcriptional suppression. |
RT-PCR of PLK mRNA in irradiated BRCA1−/− cells vs. BRCA1-reconstituted cells, CHK1 inhibitor (UCN-01) treatment |
Oncogene |
Medium |
14654792
|
| 2004 |
PLK1 physically binds to the sequence-specific DNA-binding domain of p53 and phosphorylates it, inhibiting p53 transactivation of p21WAF1, MDM2, and BAX promoters and its pro-apoptotic function; kinase-dead PLK1 fails to repress p53 transcriptional activity. |
Co-immunoprecipitation with deletion mutants, confocal co-localization, luciferase reporter assay, endogenous p21 induction assay, kinase-dead mutant analysis |
The Journal of biological chemistry |
High |
15024021
|
| 2005 |
PLK1 phosphorylation at T210 (activation loop) and S137 occurs in mitosis; DNA damage prevents phosphorylation at both sites in asynchronous cells through ATM/ATR and CHK1/CHK2 pathways; constitutively active T210D mutant is insensitive to DNA damage-induced inhibition. |
In vivo phosphopeptide mapping, T210D mutant analysis, kinase inhibitor treatments (ATM/ATR, CHK1/CHK2 inhibitors) |
Cell cycle (Georgetown, Tex.) |
Medium |
15611664
|
| 2005 |
The polo-box domain (PBD) of PLK1 interacts with MCM2 and MCM7 (and the entire MCM2-7 complex); the strongest interaction between endogenous PLK1 and Mcm7 is detected in a soluble chromatin fraction, suggesting a role for PLK1 in coordinating DNA replication and mitotic events. |
PBD-bait pulldown screen, co-immunoprecipitation, subcellular fractionation, immunoblot |
The Journal of biological chemistry |
Medium |
15654075
|
| 2007 |
TTDN1 is identified as a PLK1-interacting protein; CDK1 phosphorylates TTDN1, which is required for TTDN1-PLK1 interaction; mutation of Thr120 in TTDN1's PLK1-binding motif abolishes the interaction; TTDN1 co-localizes with PLK1 at centrosomes during mitosis and the midbody during cytokinesis. |
Yeast two-hybrid, co-immunoprecipitation, site-directed mutagenesis, immunofluorescence co-localization |
Cellular and molecular life sciences : CMLS |
Medium |
17310276
|
| 2007 |
Crystal structure of the PLK1 kinase domain with BI 2536 reveals that Leu132 in the hinge region creates a small pocket exploited by the methoxy group of BI 2536 for selectivity against non-PLK kinases; structure solved to inform structure-based drug design. |
X-ray crystallography (co-crystal structure of PLK1 KD with BI 2536) |
Chemical biology & drug design |
High |
18005335
|
| 2008 |
Crystal structure of wild-type PLK1 kinase domain in complex with DARPin 3H10 determined at 2.3 Å resolution, revealing the active conformation of PLK1; DARPin enabled crystallization by masking a surface patch rich in charged residues. |
X-ray crystallography using DARPin-assisted co-crystallization |
Acta crystallographica. Section D, Biological crystallography |
High |
18391401
|
| 2008 |
PLK-1 protein is distributed asymmetrically in C. elegans two-cell embryos with more present in the anterior AB blastomere than in P1; this asymmetry is regulated by PAR-protein-dependent anterior-posterior polarity cues through preferential protein retention; mild PLK-1 RNAi delays mitotic entry specifically in P1, promoting asynchronous cell division. |
Live imaging, RNAi knockdown, PAR mutant analysis in C. elegans embryos |
Development (Cambridge, England) |
Medium |
18305005
|
| 2010 |
PICH and PLK1 cooperate to maintain chromosome architecture during prometaphase; PICH knockdown removes PLK1 from chromosome arms causing disorganized chromosomes with open/X-shaped configuration consistent with loss of arm cohesion; chromosome disorganization is prevented by topoisomerase II inhibitor, indicating the PICH-PLK1 complex maintains architecture through topoisomerase II. |
siRNA knockdown of PICH, immunofluorescence, topoisomerase II inhibitor (ICRF-193) treatment |
Molecular biology of the cell |
Medium |
20130082
|
| 2013 |
CUL3-KLHL22 E3 ubiquitin ligase ubiquitylates PLK1 at Lys492 within the polo-box domain, causing degradation-independent dissociation of PLK1 from kinetochore phosphoreceptors; non-ubiquitylatable PLK1-K492R accumulates at kinetochores, activates the spindle assembly checkpoint, and phenocopies KLHL22 inactivation. |
Mass spectrometry identification, Co-IP, K492R mutant expression, live imaging, spindle assembly checkpoint assays |
Nature cell biology |
High |
23455478
|
| 2013 |
Aurora-A together with its cofactor Bora remains the major activator of PLK1 during mitosis (not only at G2/M transition); a small fraction of Bora is retained in mitosis, essential for continued Aurora-A-dependent T210 phosphorylation; PLK1 activation acts as a bistable switch requiring minimal Bora-Aurora-A once fully active. |
Kinase inhibitor treatments, cell synchronization, immunoblotting for pT210, siRNA knockdown of Bora |
Journal of cell science |
Medium |
24338364
|
| 2014 |
Sequential phosphorylation of procaspase-8 by CDK1/cyclin B1 (at S387, generating a PBD-docking site) and then PLK1 (at S305) during mitosis inhibits extrinsic apoptotic signaling; non-phosphorylatable S305A caspase-8 increases Fas-stimulated cell death; PLK1 inhibitor BI 2536 lowers the threshold for Fas-induced death. |
RNAi replacement strategy, phospho-site mutagenesis (S305A, S387A), co-IP with PBD, Fas stimulation apoptosis assay, PLK1 inhibitor treatment |
Molecular oncology |
High |
24484936
|
| 2014 |
PLK1 phosphorylates CLIP-170 at Ser312 during mitosis; this phosphorylation diminishes CLIP-170 binding to microtubule ends and lattice (without affecting EB3 binding); phosphorylation/dephosphorylation cycling at Ser312 is required for stable kinetochore-microtubule attachment and chromosome alignment. |
In vitro kinase assay with purified CLIP-170 N-terminal fragment, phospho-specific antibody, S312A/S312D mutant analysis, live imaging of chromosome alignment |
Cell structure and function |
High |
24451569
|
| 2014 |
DNA-PKcs physically associates with PLK1 during the mitotic phase; depletion of DNA-PKcs leads to overexpression of PLK1 through increased protein stability but attenuates recruitment of phosphorylated PLK1 to the midbody (while not affecting centrosome/kinetochore localization), resulting in cytokinesis failure. |
Co-immunoprecipitation, siRNA knockdown, immunofluorescence co-localization |
Journal of cellular biochemistry |
Medium |
24166892
|
| 2014 |
LKB1 regulates PLK1 by activating NUAK1 (ARK5), which phosphorylates MYPT1, enhancing MYPT1-PP1 binding to PLK1 and promoting PLK1 dephosphorylation; LKB1 deficiency leads to elevated phospho-PLK1 and centrosome amplification, reversed by PLK1 depletion or inhibition. |
Co-immunoprecipitation, kinase assay, siRNA, PLK1 overexpression rescue, BTO-1 inhibitor treatment |
Cell death & disease |
Medium |
24722282
|
| 2015 |
PLK-1 is required in C. elegans oocytes for nuclear envelope breakdown; partial PLK-1 inactivation causes failure to form a gap in the nuclear envelope at the interface between pronuclei and defects in chromosome congression, resulting in paired nuclei containing either maternal or paternal chromosomes in daughter cells. |
Partial RNAi inactivation, live fluorescence imaging of nuclear envelopes and chromosomes in C. elegans embryos |
Molecular biology of the cell |
Medium |
26490119
|
| 2016 |
PTEN physically associates with PLK1 and reduces PLK1 phosphorylation in a phosphatase-dependent manner; PTEN deficiency leads to elevated PLK1 phosphorylation and polyploidy; phospho-mimicking PLK1 mutant causes polyploidy similar to PTEN loss, while non-phosphorylatable PLK1 reduces the polyploid population. |
Co-immunoprecipitation, phospho-mimicking and non-phosphorylatable PLK1 mutant expression, PTEN phosphatase-dead mutant, cell ploidy analysis |
Cell cycle (Georgetown, Tex.) |
Medium |
27398835
|
| 2017 |
PLK1 phosphorylates Mre11 at S649, which primes subsequent CK2-mediated phosphorylation at S688; dual phosphorylation inhibits MRN complex loading onto damaged DNA, leading to premature DNA damage checkpoint termination and inhibition of DNA repair. |
In vitro kinase assay, phospho-site mutagenesis, chromatin loading assay, DNA damage checkpoint assays |
Cancer research |
High |
28512243
|
| 2017 |
Gravin acts as a scaffold for PLK1 at mitotic centrosomes; Gravin depletion increases PLK1 mobility (by FRAP), redistributes active PLK1, increases phosphorylation of CEP215 at S613, causes microtubule renucleation defects, chromosome misalignment, and micronuclei; a Gravin mutant unable to bind PLK1 fails to rescue these defects. |
FRAP, PLK1 FRET-based activity biosensor, shRNA knockdown, PLK1-binding-deficient Gravin mutant rescue |
Molecular biology of the cell |
High |
29282278
|
| 2017 |
PLK1 regulates NOTCH1 expression at the G2/M transition; upon DNA damage in G2, PLK1 activity is inhibited while NOTCH1 expression is maintained; PLK1-dependent signaling antagonizes NOTCH1 involvement in the DNA damage checkpoint in squamous cell carcinoma cells. |
Chemical library kinase screen, pharmacological PLK1 inhibition, co-immunoprecipitation, cell cycle synchronization, immunoblotting |
The Journal of biological chemistry |
Low |
31597699
|
| 2018 |
PLK1 overexpression causes defective cytokinesis 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, immunofluorescence of Cep55/ESCRT at abscission bridges, kinase-dead PLK1 comparison |
Nature communications |
High |
30069007
|
| 2018 |
CDK1/Aurora-A phosphorylates CtIP at S327, creating a PLK1 polo-box domain docking site; PLK1 then phosphorylates CtIP at S723; phospho-mimetic CtIP S723 fails to perform extended end resection and homologous recombination but retains ability to mediate microhomology-mediated end joining (MMEJ) while inactivating the G2/M checkpoint. |
In vitro kinase assay, phospho-site mutagenesis, MMEJ/HR reporter assays, G2/M checkpoint assay, PLK1-PBD binding assay |
Nucleic acids research |
High |
30202980
|
| 2018 |
DNA replication restricts activation of both CDK1 and PLK1; preventing DNA replication licensing and/or firing causes premature activation of CDK1 and PLK1 in S phase; inhibition of CHK1 and p38 in the presence of replication leads to premature mitotic kinase activation and replication stress. |
Double-degron system for protein depletion, kinase inhibitors, cell synchronization, CDK1/PLK1 activity reporters |
Molecular cell |
High |
30008317
|
| 2019 |
PLK1 plays dual roles in cytokinesis: PLK1 activity promotes release of centralspindlin from the spindle midzone through inhibition of PRC1, allowing centralspindlin to activate RhoA at the equatorial cortex; PLK1 inhibition sequesters centralspindlin on the midzone, making it unavailable for Aurora B-dependent RhoA activation. |
PRC1 knockdown, PLK1 inhibitor treatment, live imaging of centralspindlin and RhoA activity |
The Journal of cell biology |
Medium |
30728176
|
| 2019 |
PLK1 methyltransferase SETD6 methylates PLK1 at K209 and K413 during mitosis; loss of these methylation sites increases PLK1 kinase activity, accelerates mitotic progression and cellular proliferation; SETD6-deficient cells phenocopy non-methylatable PLK1. |
Proteomic screen, in vitro methylation assay, K209R/K413R PLK1 mutants, kinase activity assay, live cell imaging of mitotic progression |
Proceedings of the National Academy of Sciences of the United States of America |
High |
30622182
|
| 2019 |
PLK1 inhibition causes centromere disintegration driven by BLM helicase-mediated DNA unwinding at centromeres under bipolar spindle pulling force; PLK1 normally suppresses BLM activity at centromeres to maintain centromere integrity for chromosome biorientation. |
PLK1 inhibitor treatment, BLM helicase co-depletion rescue experiment, live imaging of centromere dynamics |
Nature communications |
Medium |
31253795
|
| 2019 |
PLK1 phosphorylates Gli1 at S481, promoting nuclear export of Gli1 and its binding to the negative regulator Sufu, thereby inhibiting Hedgehog signaling activity during G2/M; PLK1 inhibition prevents this phosphorylation and sustains Gli1 transcriptional activity. |
In vitro kinase assay, S481 phospho-site mutagenesis, nuclear/cytoplasmic fractionation, Gli1-Sufu co-IP, Hedgehog target gene luciferase reporter |
Journal of cell science |
High |
30578313
|
| 2019 |
Chromatin-localized PLK1 signals maintain kinetochore and centromere integrity (CENP-A, CENP-C, CENP-T, Hec1, Nuf2, Knl1 retention) against microtubule pulling forces; PICH helicase is required for centromere disruption in PLK1-inhibited cells and PICH depletion rescues kinetochore architecture; tethering PLK1 to chromatin (H2B, INCENP) but not CENP-A rescues anaphase defects. |
PLK1 inhibitor treatment, PICH siRNA rescue, chromatin-tethered PLK1 constructs (H2B-PLK1, INCENP-PLK1, CENP-A-PLK1), immunofluorescence of kinetochore components |
EMBO reports |
High |
31468671
|
| 2020 |
BRCA2 is phosphorylated by PLK1 at T207 in mitotic cells; phospho-T207 serves as a PLK1 docking site; BRCA2 bound to PLK1 forms a complex with PP2A and phospho-BUBR1; BRCA2 breast cancer variants S206C and T207A reduce PLK1 binding, causing unstable kinetochore-microtubule interactions, chromosome misalignment, and aneuploidy. |
Phospho-site identification, co-immunoprecipitation (BRCA2-PLK1-PP2A-BUBR1 complex), BRCA2 variant functional analysis, chromosome alignment assays |
Nature communications |
High |
32286328
|
| 2020 |
PLK1 is required for chromosome compaction, cohesin/condensin localization, and MTOC organization in mouse oocytes; PLK1 conditional knockout oocytes fail to form compact bivalents, develop abnormal or absent bipolar spindles due to defective C-NAP1 release and failure to recruit MTOC components and LISD factors. |
Plk1 conditional knockout mouse (oocyte-specific), immunofluorescence of cohesin, condensin, C-NAP1, MTOC components |
Molecular biology of the cell |
High |
32267211
|
| 2020 |
SET7/9 dimethylates PLK1 at K191 during early mitosis, reducing PLK1 kinase activity by limiting ATP utilization; non-methylatable PLK1 K191 mutant or SET7/9 inhibition causes mitotic arrest due to destabilized kinetochore-microtubule attachments, indicating methylation promotes dynamic attachments for error correction. |
In vitro methylation assay, K191 mutation, SET7/9 inhibitor treatment, kinetochore-microtubule attachment assay, kinase activity assay |
Journal of molecular cell biology |
High |
31863092
|
| 2020 |
BUB1 and CENP-U are the main PLK1 kinetochore receptors in mitosis; both contain a constellation of a PP2A-docking motif flanked by two PLK1-docking sites; CDK1-primed phosphorylation on these sites enables PLK1 binding and promotes PLK1 dimerization at kinetochores; this mechanism accounts for most/all kinetochore PLK1. |
Ectopic localization assay, in vitro reconstitution, kinetochore localization studies, co-IP, CDK1 priming assay, PLK1 dimerization assay |
Molecular cell |
High |
33248027
|
| 2021 |
PLK1 dimerizes during early G2 phase in a Bora-supported manner; T210 phosphorylation by Aurora-A at late G2 triggers dimer dissociation generating active PLK1 monomers; interfering with the dimer/monomer switch prevents importin association and limits nuclear shuttling, causing nuclear PLK1 mislocalization at G2/M. |
Co-immunoprecipitation of PLK1 dimers, phospho-T210 mutant analysis, importin interaction assay, live cell nuclear localization imaging |
Oncogene |
Medium |
34759346
|
| 2021 |
Apolo1 localizes to kinetochores during early mitosis and sustains PLK1 kinase activity at kinetochores (measured by FRET biosensor); Apolo1 is a PLK1 substrate, and its phosphorylation enables PP1γ to dephosphorylate and inactivate PLK1; Apolo1 constitutes a feedback loop connecting PLK1 to its own inactivation. |
FRET-based PLK1 activity reporter, co-IP, in vitro kinase assay, PP1γ interaction assay, siRNA knockdown with chromosome alignment readout |
Cell reports |
High |
34260926
|
| 2021 |
PLK1 phosphorylates PrimPol at a conserved residue between its RPA-binding motifs; this phosphorylation is cell cycle-dependent and prevents aberrant PrimPol recruitment to chromatin; loss of PLK1-dependent regulation leads to chromosome breaks, micronuclei, and reduced survival after replication stress. |
In vitro kinase assay, phospho-site identification, chromatin fractionation, siRNA, cell viability assays |
Science advances |
Medium |
34860556
|
| 2021 |
In C. elegans oocyte meiosis, BUB-1 directly recruits PLK-1 to the kinetochore and midbivalent; CENP-CHCP-4 recruits PLK-1 to chromosome arms through direct interaction; perturbing both recruitment mechanisms causes severe meiotic defects and highly aneuploid oocytes. |
Biochemical interaction assays, live imaging, C. elegans genetic mutants, co-immunoprecipitation |
eLife |
High |
37067150
|
| 2021 |
PLK1 regulates DNA replication origin firing in Xenopus by controlling origin firing frequency and synchrony; PLK1 interacts with firing factors MTBP/Treslin/TopBP1 and with Rif1; PLK1 phosphorylates Rif1 at S2058 (in its PP1-binding site), disrupting Rif1-PP1 interaction and modulating DNA replication. |
PLK1 immunodepletion in Xenopus extract, DNA fiber analysis, quantitative chromatin proteomics, co-immunoprecipitation, LC-MS/MS phosphopeptide mapping, S2058D phospho-mimetic mutant |
Nucleic acids research |
High |
34469577
|
| 2021 |
PLK1 phosphorylates DNMT3a, leading to its proteasomal degradation during mitosis; DNMT3a in turn represses PLK1 transcription in interphase, constituting a negative feedback loop; combined inhibition of PLK1 and DNMT3a suppresses prostate cancer synergistically through autophagy regulation. |
Co-IP, kinase assay, DNMT3a stability assay upon PLK1 activation, PLK1 promoter analysis |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) |
Medium |
34051063
|
| 2021 |
PLK1 activity is essential for time-dependent release of 53BP1 from kinetochores; PLK1 inhibition causes 53BP1 persistence at kinetochores (via CENP-F docking), preventing cytosolic 53BP1 association with p53 and blunting the mitotic surveillance pathway; CENP-F-53BP1 binding disruption has no impact on mitotic timing, indicating cytosolic (not kinetochore) 53BP1 measures mitotic duration. |
PLK1 inhibitor treatment, CENP-F-53BP1 binding mutant, immunofluorescence quantification of kinetochore/cytosolic 53BP1, p53 activation assay |
EMBO reports |
Medium |
37888778
|
| 2021 |
PLK1 and Aurora-A are both required for centrosome maturation and separation prior to metaphase I in mouse spermatocytes; PLK1 is additionally required to block premature second-round centriole duplication until anaphase I, maintaining strict spatiotemporal control of centrosome biogenesis during meiosis. |
Germ cell-specific conditional knockout of Plk1 and Aurora-A, immunofluorescence of centriole/centrosome markers through meiotic progression |
EMBO reports |
High |
33615678
|
| 2022 |
PLK1 promotes NLRP3 inflammasome activation during cell interphase; PLK1 is in close proximity to and interacts with NLRP3; mechanistically, PLK1 orchestrates the MTOC structure and NLRP3 subcellular positioning upon inflammasome activation; pharmacological PLK1 inhibition suppresses IL-1β production in vivo. |
BioID proximity-labeling screen, co-immunoprecipitation, domain interaction mapping, pharmacological PLK1 inhibition, in vivo endotoxemia and peritonitis mouse models |
The Journal of clinical investigation |
Medium |
37698938
|
| 2022 |
Pathogenic BRCA1 mutations reduce BRCA1 function, leading to elevated PLK1 activity, which specifically disrupts cell division axis orientation in mammary cells; this defect is independent of accumulated DNA damage and depends on PLK1 activity, as shown by 15 genetically edited BRCA1 mutant cell lines. |
Primary mammary cell division axis imaging, BRCA1-mutant genetically-edited cell lines, PLK1 activity measurements, genetic and pharmacological PLK1 inhibition |
Nature communications |
Medium |
35459234
|
| 2022 |
PLK1-mediated phosphorylation of RB at S758 inhibits NF-κB nuclear translocation, inactivating the NF-κB pathway; PLK1 inhibition or depletion therefore activates NF-κB, upregulating PD-L1 expression in pancreatic ductal adenocarcinoma cells. |
In vitro kinase assay for RB-S758 phosphorylation, NF-κB nuclear translocation assay, PD-L1 expression analysis, siRNA and pharmacological PLK1 inhibition |
Cancer research |
Medium |
35950917
|
| 2023 |
BUB-1-bound PLK-1 is required for CDC-20 kinetochore recruitment and timely mitotic progression in C. elegans embryos; PLK-1 kinase activity phosphorylates the CDC-20-binding ABBA motif of BUB-1 to promote BUB-1-CDC-20 interaction; a conserved STP motif in BUB-1 that docks PLK-1 is necessary for this function. |
C. elegans genetics (STP motif mutation in BUB-1), live imaging, in vitro kinase assay of ABBA motif phosphorylation, CDC-20 localization analysis |
Current biology : CB |
High |
37137308
|
| 2023 |
PLK1 phosphorylates DNA polymerase theta (Polθ) in mitosis, activating it; phosphorylated Polθ is recruited to mitotic DSBs through direct interaction with BRCA1 C-terminal domains of TOPBP1; Polθ-mediated end joining repairs mitotic DSBs and maintains genome integrity; loss of Polθ is synthetically lethal with homologous recombination deficiency. |
In vitro kinase assay, co-IP (Polθ-TOPBP1 interaction), mitotic DSB repair assay, synthetic lethality assay (HR-deficient cells) |
Nature |
High |
37674080
|
| 2023 |
PLK1 maintains lysosomal function in renal tubular cells by phosphorylating the V-ATPase subunit ATP6V1A to regulate intralysosomal pH; PLK1 inhibition or knockout impairs lysosomal acidification and blocks autophagic flux, leading to reduced fibroblast activation and attenuation of renal tubulointerstitial fibrosis. |
Plk1 knockout mice (UUO model), pharmacological PLK1 inhibition, ATP6V1A phosphorylation assay, lysosomal pH measurement, autophagic flux assay |
Cell death & disease |
Medium |
37640723
|
| 2024 |
PLK1 promotes CENP-A deposition (centromere maintenance) in early G1 by recognizing self-primed phosphorylations of Mis18α (Ser54) and Mis18BP1 (Thr78, Ser93) through its polo-box domain; PLK1 binding activates Mis18α-Mis18β and promotes Mis18 complex-HJURP interaction required for CENP-A loading. |
Biochemical phosphorylation mapping, PLK1-PBD binding assays, CENP-A deposition assay, HJURP co-IP, phospho-site mutagenesis |
Science (New York, N.Y.) |
High |
39236163 39236175
|
| 2019 |
PP2A-B55 (α and δ isoforms) directly interacts with PLK1 during recovery from mitotic DNA damage; dephosphorylation of PLK1 by PP2A-B55 is induced through ATM/CHK1/CHK2-dependent repression of the Greatwall/ENSA pathway, leading to PP2A-B55 liberation and PLK1 dephosphorylation and mitotic slippage. |
Co-immunoprecipitation of PLK1-PP2A-B55α/δ, siRNA depletion of PP2A-B55, immunoblotting for phospho-PLK1, Greatwall/ENSA pathway manipulation |
Cell cycle (Georgetown, Tex.) |
Medium |
31072185
|
| 2017 |
PLK1 phosphorylates Numb, promoting its proteasomal degradation; loss of Numb impairs the Numb/p53 pathway, providing a mechanism by which PLK1 antagonizes p53 during DNA damage response; cancer cells with non-phosphorylatable Numb show increased sensitivity to doxorubicin. |
In vitro kinase assay, phospho-site mutagenesis, proteasomal degradation assay, p53 stabilization assay, xenograft model |
Oncogene |
Medium |
29059161
|