| 2002 |
CDK1 (Cdc2) forms a stoichiometric heterodimeric complex with cyclin B, and the cyclin subunit is necessary for CDK1 to gain protein kinase activity; this complex constitutes MPF (maturation-promoting factor) that controls entry into M phase. |
Biochemical purification, sequencing of cyclin B from purified starfish MPF, reconstitution in invertebrate eggs and vertebrate cells |
Journal of cell science |
High |
12045216
|
| 2005 |
CDK1 directly phosphorylates Swe1 (yeast Wee1), first activating Swe1 and promoting formation of a stable Swe1-CDK1 inhibitory complex, and then further phosphorylating Swe1 to release and activate CDK1; thus CDK1 both positively and negatively regulates its own inhibitor. |
In vitro kinase assay, co-immunoprecipitation, phosphorylation site mutagenesis in budding yeast |
Cell |
High |
16096060
|
| 2004 |
Drosophila Wee1 (dWee1) phosphorylates CDK1 at tyrosine 15 to inhibit its activity and time mitotic entry; loss of maternal dwee1 causes premature mitosis, spindle defects, and embryonic lethality. |
Genetic loss-of-function (dwee1 mutant embryos), in vitro kinase assay, Chk2-dependent developmental block as phenotypic readout |
Current biology |
High |
15589158
|
| 2003 |
Binding of cyclin B1 to CDK1 initiates conformational changes allowing CDK1 to alter its phosphorylation status and become an active kinase; the active cyclin B1-CDK1 complex must translocate to the nucleus (via phosphorylation of cyclin B1 within the CRS region) to phosphorylate nuclear substrates at mitotic onset. |
Biochemical analysis, phosphorylation studies, nuclear import/export assays |
Progress in cell cycle research |
Medium |
14593728
|
| 1997 |
CDK1 inactivation (by expression of non-destructible cyclin B) inhibits chromosome decondensation, nuclear envelope formation, and cytokinesis, and prevents formation of the central anaphase spindle and equatorial organization of F-actin/myosin II, demonstrating that CDK1 inactivation is required to drive anaphase spindle dynamics and cytokinesis. |
mRNA microinjection of non-destructible cyclin BΔ90 into prometaphase cells, rhodamine-tubulin injection, F-actin/myosin II localization by immunofluorescence |
The Journal of cell biology |
High |
9230080
|
| 2013 |
Aurora B and CDK1 phosphorylate Sororin, which destabilizes the Sororin-Pds5 interaction, releases acetylated cohesin from chromosome arms, and promotes loss of cohesion; centromeric PP2A-Sgo1 opposes this by dephosphorylating Sororin. |
In vitro kinase assay, co-immunoprecipitation, phospho-site mutagenesis, cell-based chromosome cohesion assays |
Proceedings of the National Academy of Sciences |
High |
23901111
|
| 2011 |
CDK1 phosphorylates Sororin, causing its release from chromatin and cohesin in mitosis; hypophosphorylated Sororin associates with DNA and cohesin and increases sister chromatid cohesion, while CDK1-phosphorylated Sororin loses chromatin association. |
CDK1 phosphorylation site mutagenesis, DNA-cellulose pull-down, co-immunoprecipitation, sister chromatid cohesion assays |
Journal of cell science |
High |
21878504
|
| 2007 |
G1 cyclin-CDK1 complexes in budding yeast specifically phosphorylate multiple proteins associated with Cdc24 (the GEF for Cdc42), and a Cdc24-associated protein with mutated CDK1 phosphorylation sites causes bud growth defects, linking CDK1 directly to control of polarized cell growth. |
Mass spectrometry identification of CDK1 substrates, phosphorylation site mutagenesis, bud growth phenotype analysis |
Nature cell biology |
High |
17417630
|
| 2013 |
CDK1 (with Cdc5/PLK1) activates Mus81-Mms4 via phosphorylation in late G2/M to drive resolution of DNA damage-tolerance recombination intermediates; premature activation of this pathway causes crossover-associated chromosomal translocations. |
Phosphomimetic/phospho-deficient Mms4 variants, genetic epistasis in S. cerevisiae, checkpoint-deficient backgrounds |
The EMBO journal |
High |
23531881
|
| 2015 |
CDK1-cyclin B1 directly hyperphosphorylates 4E-BP1 at authentic mTOR phosphorylation sites during mitosis, generating a mitosis-specific δ-isoform resistant to mTOR inhibition; this maintains cap-dependent protein translation during mitosis. |
In vitro kinase assay with recombinant CDK1/CYCB1 and 4E-BP1, mTOR inhibitor resistance assay, reticulocyte translation reconstitution, Click-iT flow cytometry for protein synthesis |
Proceedings of the National Academy of Sciences |
High |
25883264
|
| 2018 |
CDK1 in complex with cyclin A2 promotes adhesion complex organization and actin cytoskeleton organization during interphase (S phase); elevated cyclin B1 and subsequent inhibitory phosphorylation of CDK1 triggers adhesion complex disassembly in G2 and entry into mitosis. |
Cell synchronization, CDK1 inhibition, cyclin knockdown/overexpression, high-content imaging of focal adhesion dynamics |
The Journal of cell biology |
High |
29930204
|
| 2020 |
CDK1-cyclin B phosphorylates human cGAS at S305 (mouse S291), inhibiting its ability to synthesize cGAMP during mitosis and thus preventing innate immune sensing of self-DNA upon nuclear envelope breakdown; PP1 dephosphorylates cGAS upon mitotic exit to restore DNA sensing. |
In vitro kinase assay, phospho-site mutagenesis, cGAMP synthesis assay, cell-based mitotic entry/exit experiments |
Cell discovery |
High |
32351706
|
| 2018 |
CDK1 (priming kinase) phosphorylates BUB1 and CENP-U at PLK1-docking sites at kinetochores; this CDK1-primed phosphorylation enables PLK1 recruitment to kinetochores and promotes PLK1 dimerization, constituting the main PLK1 kinetochore-targeting mechanism. |
Ectopic localization assay, in vitro reconstitution, kinetochore localization studies, phospho-site mutagenesis |
Molecular cell |
High |
33248027
|
| 2019 |
CDK1-CCNB1 phosphorylates MPS1 at S281, enabling MPS1 recruitment to unattached kinetochores and spindle checkpoint signaling; PP2A-B55, negatively regulated by CDK1-CCNB1, delays MPS1 S281 dephosphorylation to extend the checkpoint-responsive period. |
Phospho-site mutagenesis, kinetochore tethering bypass experiments, cell cycle synchronization, kinase/phosphatase inhibition |
The Journal of cell biology |
High |
30674582
|
| 2019 |
CDK1-CCNB1 localizes to unattached kinetochores via interaction with the first 100 amino acids of MAD1 (in an MPS1-dependent manner), creating a positive feedback loop for MPS1 kinetochore recruitment and sustained spindle checkpoint arrest. |
Proteomic analysis, co-immunoprecipitation, kinetochore localization studies, live cell imaging |
The Journal of cell biology |
High |
30674583
|
| 2020 |
In embryonic stem cells, CDK1 phosphorylates chromatin-bound proteins including Dot1l (H3K79 methyltransferase), partially inactivating it; decrease in CDK1 activity during differentiation de-represses Dot1l and allows coordinated expression of differentiation genes. |
Analog-sensitive CDK1 knockin mice, quantitative phosphoproteomics, histone modification profiling, Dot1l activity assays |
Molecular cell |
High |
32240602
|
| 2015 |
CDK1-cyclin B1 phosphorylates SIRT3 at Thr150/Ser159, enhancing SIRT3 deacetylase activity in mitochondria; cells expressing Thr150Ala/Ser159Ala-mutant SIRT3 show reduced mitochondrial deacetylation, membrane potential, MnSOD activity, and ATP generation, and increased radiation sensitivity. |
In vitro kinase assay, phospho-site mutagenesis, mitochondrial fractionation, mitochondrial functional assays, clonogenic survival, xenograft |
Molecular cancer therapeutics |
High |
26141949
|
| 2015 |
CDK1 relocates to mitochondria upon genotoxic stress and phosphorylates complex I subunits, boosting mitochondrial ATP generation to fuel nuclear DNA repair; cells with CDK1 phosphorylation-deficient complex I subunits show compromised mitochondrial ATP and DNA repair. |
Mitochondrial fractionation, in vitro kinase assay, phospho-site mutagenesis of complex I subunits, oxygen consumption and ATP measurement, DNA repair assay |
Cell reports |
High |
26670043
|
| 2012 |
During mitosis, CDK1 phosphorylates CLASP2 at S1234, priming CLASP2 for association with PLK1; PLK1 recruitment to kinetochores is enhanced by this phosphorylation and is required to stabilize kinetochore-microtubule attachments for chromosome alignment. |
In vitro kinase assay, phospho-site mutagenesis, kinetochore localization, chromosome alignment assays |
The Journal of cell biology |
High |
23045552
|
| 2015 |
CDK1 directly phosphorylates Ajuba at Ser119 and Ser175 during G2/M; mitotic phosphorylation of Ajuba is sufficient to promote cell proliferation and anchorage-independent growth in vitro and tumorigenesis in vivo, independently of Hippo pathway effects. |
In vitro kinase assay, phospho-site mutagenesis, cell proliferation assays, anchorage-independent growth, in vivo tumorigenesis |
The Journal of biological chemistry |
High |
27226586
|
| 2015 |
CDK1 phosphorylates TAZ at S90, S105, T326, and T346 during G2/M, inactivating TAZ oncogenic activity; non-phosphorylatable TAZ-5A has higher transcriptional activity and causes greater spindle/centrosome defects than wild-type TAZ. |
In vitro kinase assay, phospho-site mutagenesis, EMT assay, anchorage-independent growth, mitotic spindle analysis |
Oncotarget |
High |
26375055
|
| 2015 |
CDK1 phosphorylates the Smc4 subunit of condensin at multiple sites; this multisite phosphorylation acts as a high-sensitivity switch that drives chromosome condensation at mitotic entry, and its abrogation causes chromosome segregation defects and lethality. |
Phospho-site mutagenesis of Smc4, CDK1 activity titration, chromosome segregation assays in budding yeast |
Genes & development |
High |
25691469
|
| 2016 |
CDK1-CyclinB inhibits PLK4-STIL complex formation in mitosis by binding STIL, thereby preventing untimely centriole biogenesis; after CDK1-CyclinB inactivation at mitotic exit, PLK4 can bind and phosphorylate STIL in G1 to initiate pro-centriole assembly. |
Co-immunoprecipitation, phosphorylation assays, in vitro kinase assay, cell cycle synchronization experiments |
Current biology |
High |
27112295
|
| 2016 |
CDK1 phosphorylates WRN at S1133, promoting WRN interaction with the MRE11 complex and enabling DNA2-dependent long-range resection at replication-associated DSBs, thereby promoting homologous recombination and suppressing NHEJ. |
In vitro kinase assay, phospho-site mutagenesis, co-immunoprecipitation (WRN-MRE11), DNA resection assays, HR/NHEJ pathway choice assay |
Nature communications |
High |
27634057
|
| 2020 |
CDK1 phosphorylates hTERT at threonine 249 during mitosis; this phosphorylation is required for hTERT RNA-dependent RNA polymerase (RdRP) activity but dispensable for reverse transcriptase activity, and regulates expression of genes necessary for cancer cell proliferation. |
CRISPR/Cas9 endogenous mutagenesis, in vitro kinase assay, CAGE transcriptomics, RdRP activity assay |
Nature communications |
High |
32214089
|
| 2020 |
CDK1 phosphorylates ULK1 and ATG13 (of the ULK1-ATG13 autophagy initiation complex) during mitosis, promoting mitotic autophagy and cell cycle progression; double knockout of ULK1 and ATG13 blocks cell cycle progression. |
Mass spectrometry, site-directed mutagenesis, in vitro kinase assay, ULK1/ATG13 double KO mouse/cell models |
PLoS biology |
High |
32516310
|
| 2020 |
CDK1 phosphorylates LARP1, and this phosphorylation is required for CDK1's strong positive effect on translation of 5'TOP mRNAs (encoding ribosomal proteins and translation factors), coupling cell proliferation with biosynthesis of the translation machinery. |
Kinase/phosphatase screen, cell synchronization, Ribo-Seq, LARP1 phosphorylation analysis, stress granule formation assay |
The Journal of cell biology |
High |
32040547
|
| 2014 |
CDK1/cyclin B1 phosphorylates procaspase-8 at S387, creating a phospho-epitope for PLK1's polo-box domain binding; subsequent PLK1 phosphorylation of S305 inhibits caspase-8 activation, reducing sensitivity to extrinsic apoptosis during mitosis. |
In vitro kinase assay, RNAi replacement with phospho-mutants, Fas-stimulated death receptor assay |
Molecular oncology |
High |
24484936
|
| 2015 |
CDK1 phosphorylation of RepoMan reduces PP1 binding to RepoMan but facilitates PP2A-B56 recruitment; upon CDK1 inactivation in early anaphase, this phosphatase switch is reversed, accumulating PP1-RepoMan to inactivate Aurora B and initiate nuclear envelope reassembly. |
In vitro kinase assay, phospho-site mutagenesis, phosphatase binding assays, live-cell imaging of mitotic exit events |
Nature communications |
High |
26674376
|
| 2020 |
CDK1 phosphorylates the PP2A catalytic subunit (PP2Ac) at a threonine residue, disrupting its holoenzyme formation with regulatory subunit B55, thereby decreasing dephosphorylation of PP2A-B55 substrates and promoting mitotic entry. |
Chemical proteomics enrichment of PPP holoenzymes, mass spectrometry, kinase profiling, in vitro phosphorylation |
Science signaling |
High |
32900880
|
| 2008 |
CDK1 directly phosphorylates the vacuole inheritance adaptor Vac17 in budding yeast, promoting Vac17 interaction with the myosin V motor Myo2 and coordinating vacuole movement with cell cycle progression. |
In vitro kinase assay, phospho-site mutagenesis, co-immunoprecipitation, vacuole inheritance assay |
Developmental cell |
High |
18804442
|
| 2017 |
CDK1-cyclin B activity generates a spatiotemporal gradient from the nucleus in starfish oocytes that drives surface contraction waves by activating RhoA/RhoA kinase/myosin II at the wave front (via removal of CDK1 inhibition of RhoA module) and negative feedback at the rear. |
Quantitative live imaging, biochemical perturbations, mathematical modeling, CDK1 activity manipulation |
Nature communications |
High |
29021609
|
| 2012 |
CDK1 phosphorylates KIBRA at Ser542 and Ser931 in response to spindle damage; CDC14A/B phosphatases associate with KIBRA and dephosphorylate these CDK1 sites; this CDK1/CDC14-dependent phosphoregulation of KIBRA is involved in mitotic exit under spindle stress. |
In vitro kinase assay, phospho-site mutagenesis, co-immunoprecipitation, in vitro phosphatase assay, inducible expression cell lines |
The Biochemical journal |
High |
22784093
|
| 2019 |
CDK1 phosphorylates TFCP2L1 (a pluripotency transcription factor) at Thr177, affecting ESC cell cycle progression, pluripotency, and differentiation; CDK1-mediated TFCP2L1 phosphorylation also drives bladder cancer cell proliferation, self-renewal, and invasion. |
In vitro kinase assay, phospho-site mutagenesis (Thr177), ESC differentiation assays, xenograft tumor model |
EMBO molecular medicine |
High |
31709755
|
| 2014 |
CDK1 (and PKCδ) bind Drp1 and phosphorylate it at Ser616, activating Drp1-mediated mitochondrial fission; inhibition of CDK1 attenuates pSer616 Drp1, mitochondrial fission, and cardiomyocyte death during anoxia-reoxygenation injury. |
Co-immunoprecipitation, phospho-specific antibody detection, CDK1 inhibitor treatment, mitochondrial morphology assay, cell death assay |
Biochemical and biophysical research communications |
Medium |
25445585
|
| 2016 |
CDK1 phosphorylates Bora (SPAT-1 in C. elegans) at conserved Sp/Tp residues, which is essential for Aurora A-dependent PLK1 activation and mitotic entry; this mechanism also operates during DNA damage checkpoint recovery in mammalian cells. |
Phospho-site mutagenesis of Bora, FRET-based PLK1 activity biosensor, C. elegans genetics, mammalian checkpoint recovery assays |
Cell cycle |
High |
27831827
|
| 2019 |
CDK1 and CDK2 phosphorylate NICD1 (Notch intracellular domain), targeting it for SCF E3 ligase-dependent degradation in a cell cycle-dependent manner; inhibiting CDK1 or CDK2 increases NICD levels, delays segmentation clock gene oscillations, and increases somite size. |
In vitro kinase assay, phospho-site mutagenesis, CDK inhibitor treatment, in vivo somitogenesis assay |
EMBO reports |
High |
31267714
|
| 2021 |
CDK1 phosphorylates CHMP7 at Ser3 and Ser441 upon mitotic entry, reducing CHMP7 interaction with LEM2 and suppressing ESCRT-III assembly during M phase; spatiotemporal dephosphorylation of CHMP7 by CDK1 inactivation licenses ESCRT-III-dependent nuclear envelope reformation during telophase. |
Live cell imaging, protein biochemistry, phospho-site mutagenesis, CDK1 inhibition |
eLife |
High |
34286694
|
| 2019 |
CDK1-cyclin B1 phosphorylates importin-α1 at Thr9 and Ser62 during mitosis, inhibiting its binding to importin-β and promoting release of spindle assembly factors TPX2 and KIFC1 to the spindle; non-phosphorylatable importin-α1 causes shortened spindles and prolonged metaphase. |
Phospho-site mutagenesis, importin-β binding assay, spindle assembly phenotype analysis, live cell imaging |
Journal of cell science |
High |
31434716
|
| 2020 |
CDK1 phosphorylates NuMA at Thr2055, negatively regulating its cortical localization; PP2A-B55γ (PPP2CA-B55γ-PPP2R1B complex) dephosphorylates NuMA T2055 to restore cortical dynein and ensure proper mitotic spindle orientation. |
In vitro reconstitution of phosphatase activity, phospho-site mutagenesis, cortical NuMA localization assay, spindle orientation phenotype |
Journal of cell science |
High |
32591484
|
| 2022 |
CDK1-cyclin B1 phosphorylates kindlin during mitotic entry, leading to recruitment of the cullin 9-FBXL10 ubiquitin ligase complex that ubiquitinates and degrades kindlin, driving focal adhesion disassembly and cell rounding at mitotic entry. |
Phospho-site mutagenesis, co-immunoprecipitation of ubiquitin ligase, ubiquitination assay, FA disassembly phenotype, live cell imaging |
Nature cell biology |
High |
35469017
|
| 2019 |
CDK1 phosphorylates Sox2, increasing its phosphorylation, nuclear translocation, and transcriptional activity; blockade of CDK1 reduces Sox2 nuclear localization and activity, and knockout of Sox2 abolishes CDK1-driven tumor-initiating capacity in melanoma. |
Proteomic analysis (Co-IP-MS), CDK1 overexpression/inhibition, Sox2 knockdown/knockout, nuclear localization assay, sphere-forming and xenograft assays |
Cancer research |
Medium |
30297536
|
| 2017 |
CDK1-cyclin B1 phosphorylates XIAP at S40, inhibiting XIAP's binding to activated effector caspases and abolishing its anti-apoptotic function; phosphomimetic S40D mutation sensitizes cells to apoptosis during mitotic arrest, while non-phosphorylatable S40A blocks apoptosis. |
In vitro kinase assay, phospho-site mutagenesis, caspase binding assay, live-cell imaging of apoptosis during mitotic arrest |
Journal of cell science |
High |
27927753
|
| 2017 |
CDK1 phosphorylates PBK at Thr9, Thr24, Ser32, and Ser59 during mitosis; phosphorylation of Thr9 is required for cytokinesis, and non-phosphorylatable PBK-T9A augments tumorigenesis, indicating CDK1-mediated phosphorylation inhibits PBK's oncogenic activity. |
In vitro kinase assay, phospho-site mutagenesis, cytokinesis phenotype assay, tumorigenesis assay |
Cellular signalling |
High |
28780319
|
| 2000 |
CDK1 negatively regulates APC/C activation by the Cdh1/Fzr co-activator, preventing premature cyclin degradation; Fzr overexpression or CDK1 inhibition can override the prometaphase checkpoint, and mammalian Cdc14 phosphatase contributes to this pathway. |
CDK1 inhibitor treatment, Fzr overexpression, spindle checkpoint assay, mammalian cell-based cyclosome activity assay |
Experimental cell research |
High |
10694434
|
| 2012 |
CDK1 phosphorylates MYT1 inhibitory kinase contributes context: MYT1 (not WEE1) has a rate-determining role in checkpoint recovery — depletion of MYT1 causes precocious mitotic entry when checkpoint is abrogated by CHK1 or WEE1 inhibitors, by lowering the threshold for CDK1 activation. |
MYT1 siRNA depletion, CHK1/WEE1 inhibitor treatment, time-lapse microscopy, clonogenic survival, xenograft |
Oncogene |
Medium |
23146904
|
| 2020 |
CDK1 directly phosphorylates USP9X at serine 2563, activating its deubiquitinase activity; activated USP9X stabilizes WT1 (Wilms' tumor protein 1), which functions as a mitotic transcription factor driving CXCL8/IL-8 expression for mitotic survival; CDC14B phosphatase opposes this by dephosphorylating USP9X. |
Proteome-wide phosphorylation screen, in vitro kinase assay, ubiquitination/deubiquitination assays, WT1 transcription assays |
Nature communications |
High |
32152317
|
| 2021 |
USP7 interacts with PP2A and supports active PP2A localization in the cytoplasm; inhibition of USP7 leads to widespread CDK1 activation throughout the cell cycle, producing CDK1 target phosphorylation and DNA damage; toxicity is alleviated by lowering CDK1 activity or activating PP2A. |
USP7 inhibitor treatment, CDK1 inhibitor rescue, phosphoproteomics, co-immunoprecipitation (USP7-PP2A) |
The EMBO journal |
Medium |
33856059
|
| 2020 |
CDK1 phosphorylates the Dam1 complex subunit Ask1 in budding yeast, increasing Dam1 complex residence time on microtubules and enhancing kinetochore-microtubule attachment strength via promotion of Dam1 oligomerization. |
In vitro reconstitution with purified components, single-molecule microtubule attachment assay, phospho-site mutagenesis of Ask1 |
Current biology |
High |
32946748
|
| 2021 |
CKS1 has a proteome-wide role as an enhancer of multisite CDK1 phosphorylation; Cyclin A and CKS1 together promote CDK1 phosphorylation at non-proline-directed sites (preferably with +3 lysine), contrary to the classical model of CDK1 as exclusively proline-directed. |
Fixed-cell kinase assay, quantitative phosphoproteomics, recombinant CDK1 complex reconstitution with Cyclin A/B and CKS1 |
Cell reports |
High |
36840943
|
| 2022 |
A fraction of CDK1 bound to spindle structures is maintained in an inhibited (phosphorylated) state by Wee1 even in mitosis; this 'compartmentalized' inactive CDK1 (i-Cdk1) is required for spindle assembly, as loss of i-Cdk1 inhibits spindle assembly and its restoration promotes it. |
Live cell imaging, immunofluorescence, CDK1 inhibitor and Wee1 inhibitor treatment, Cdc25 exclusion from spindle-bound CDK1 |
Cell reports |
Medium |
35081344
|
| 2022 |
Nuclear-cytoplasmic compartmentalization of cyclin B1-CDK1 modulates cell cycle clock properties: in nucleus-present cells, CDK1 frequency remains constant against cyclin B1 variations (robust mitotic phase duration), and active cyclin B1-CDK1 accumulates in nuclei without delay until nuclear envelope breakdown triggers anaphase. |
FRET biosensor for CDK1 activity in reconstituted cells with or without nucleus, quantitative live-cell imaging |
Cell reports |
High |
36577372
|
| 2021 |
Reconstituted ternary CDK1:Cyclin-B:CKS1 complex is more active than binary CDK1:Cyclin-B; CDK1 kinase activity requires T-loop phosphorylation by CDK-activating kinase (CAK); CKS1 boosts CDK1 processivity for multisite substrate phosphorylation. |
Recombinant protein reconstitution in insect cells and in vitro with purified CAKs, in vitro kinase assay comparing binary/ternary complexes |
Protein science |
High |
34791727
|
| 2022 |
S6K1 phosphorylates CDK1 at serine 39, causing G2/M cell cycle arrest and enabling homologous recombination DNA repair; this places CDK1 downstream of the mTORC1-S6K1 pathway as a regulator of DNA repair pathway choice. |
In vitro kinase assay, phospho-site mutagenesis, cell cycle analysis, HR repair assay |
eLife |
Medium |
36189922
|
| 2023 |
CDK1 directly binds and phosphorylates ACSL4 at S447, recruiting E3 ubiquitin ligase UBR5 and causing polyubiquitination and degradation of ACSL4, thereby reducing polyunsaturated fatty acid lipid biosynthesis, inhibiting ferroptosis, and conferring oxaliplatin resistance in colorectal cancer. |
Co-immunoprecipitation, in vitro kinase assay, ubiquitination assay, CRISPR/Cas9 screen, cell/patient-derived xenograft models |
Advanced science |
High |
37428466
|
| 2023 |
CDK1 directly phosphorylates USP29, activating its deubiquitinase activity toward TWIST1, stabilizing TWIST1 and driving EMT, cancer stem cell features, and chemotherapy resistance in triple-negative breast cancer. |
In vitro kinase assay, deubiquitinase activity assay, co-immunoprecipitation, TWIST1 stability analysis, in vitro/in vivo tumor models |
Advanced science |
High |
36782089
|
| 2023 |
CDK1 directly phosphorylates pVHL at Ser80, priming recognition by PIN1 isomerase, which then facilitates recruitment of E3 ligase WSB1, leading to pVHL ubiquitination and degradation, thereby promoting tumor progression. |
In vitro kinase assay, co-immunoprecipitation, ubiquitination assay, CDK1 inhibitor (RO-3306) treatment, in vivo xenograft |
Cell death and differentiation |
High |
36813923
|
| 2023 |
YOD1 (OTUD2) deubiquitinase binds CDK1, removes its ubiquitin chains, and stabilizes CDK1 protein by preventing its degradation; this stabilization promotes TNBC proliferation and tumor progression. |
Co-immunoprecipitation, ubiquitination/deubiquitination assay, YOD1 knockdown, in vitro and in vivo tumor models |
Journal of experimental & clinical cancer research |
Medium |
37667382
|
| 2024 |
OTUD4 deubiquitinase directly interacts with CDK1 and stabilizes it by removing K11-, K29-, and K33-linked polyubiquitin chains; OTUD4 also indirectly stabilizes CDK1 via FGFR1 stabilization, resulting in MAPK pathway activation and GBM progression. |
Co-immunoprecipitation, ubiquitination assay (linkage-specific), in vitro DUB assay, in vitro/in vivo GBM models |
Cell death & disease |
Medium |
38429268
|
| 2022 |
USP14 deubiquitinase interacts with CDK1 and stabilizes it by removing K48-linked ubiquitin chains, preventing CDK1 degradation; USP14 inhibition causes G2/M arrest and reduces CDK1 protein levels in breast cancer cells. |
Co-immunoprecipitation, K48-linked ubiquitination assay, flow cytometry cell cycle analysis, CDK1 protein stability assay |
Acta biochimica et biophysica Sinica |
Medium |
36604147
|
| 2018 |
DNA replication provides an inhibitory signal that restricts CDK1 and PLK1 activation; prevention of DNA replication licensing/firing leads to premature CDK1 and PLK1 activation in S phase, and CHK1/p38 inhibition in the presence of ongoing replication induces severe replication stress via premature CDK1/PLK1 activation. |
Double-degron degradation system, kinase inhibitors, DNA replication inhibition, CDK1/PLK1 activity monitoring |
Molecular cell |
High |
30008317
|
| 2011 |
CDK1 phosphorylation of the kinetochore protein Nsk1 in fission yeast antagonizes its kinetochore and spindle localization during early mitosis; non-phosphorylatable Nsk1 binds prematurely, cementing improper kinetochore-microtubule attachments and causing chromosome mis-segregation. |
Phospho-site mutagenesis of Nsk1, kinetochore/spindle localization assay, chromosome segregation phenotype analysis in S. pombe |
The Journal of cell biology |
High |
22065639
|
| 2019 |
CDK1 phosphorylates the transcription factor Hcm1 at distinct site clusters in budding yeast: one cluster activates Hcm1 (promoting S-phase gene expression) and another targets it for degradation; calcineurin phosphatase specifically removes activating phosphates to slow proliferation under stress. |
Phospho-site mutagenesis, Hcm1 transcriptional activity assay, calcineurin inhibition, stress response assays |
Molecular biology of the cell / Current genetics |
Medium |
26269584 26590602
|
| 2021 |
CDK1-Clb2-Cks1 multisite phosphorylation of the transcriptional co-activator Ndd1 first promotes CLB2 gene transcription (positive feedback at low CDK1 activity) and then, at high CDK1 activity, triggers Ndd1 degradation (delayed negative feedback), producing a pulse of mitotic gene expression. |
Phospho-site mutagenesis of Ndd1, CLB2 reporter assay, CDK1 activity titration, Cks1/Clb2 phosphate-binding pocket mutations |
Current biology |
High |
34818519
|
| 2017 |
CDK1 and PLK1 coordinate disassembly and reassembly of the nuclear envelope during vertebrate mitosis via independent regulatory pathways: Lamin A/C targeting to chromatin is controlled by CDK1 activity (clock-based model), while NPC loading is spatially monitored by PLK1. |
CDK1 and PLK1 inhibitor treatment, live cell imaging of NE components, micronuclei analysis |
Oncotarget |
Medium |
29487689
|