| 1987 |
A human homologue of the fission yeast cdc2 gene was cloned by complementation of a cdc2 mutant in fission yeast, establishing that the cell cycle control mechanism is conserved between yeast and humans. |
Functional complementation of S. pombe cdc2 mutant with human cDNA library |
Nature |
High |
3553962
|
| 1988 |
Human p34cdc2 is phosphorylated at multiple sites, associates with p62 (cyclin B), and its kinase activity is cell cycle-regulated, peaking during mitotic metaphase; the complex is inactive in early G1 and maximally active at G2/M. |
Cell fractionation, immunoprecipitation, in vitro kinase assay, cell synchronization |
Cell |
High |
3289755
|
| 1989 |
Cdc2 protein kinase forms separate complexes with cyclin A and cyclin B; these complexes display cell cycle-dependent histone H1 kinase activity, and cyclin proteolysis at the end of mitosis inactivates MPF. |
Immunoprecipitation with anti-cyclin A/B antibodies, p13suc1-Sepharose pulldown, in vitro histone H1 kinase assay |
Cell |
High |
2538242
|
| 1989 |
Human cyclin B1 associates with p34cdc2 during G2/M phase, and this complex has histone H1 kinase activity; cyclin B1 is present in the cytoplasm during interphase and enters the nucleus at mitosis onset. |
Immunoprecipitation, in vitro kinase assay, cell cycle synchronization |
Cell |
High |
2570636
|
| 1989 |
CDK1 (p34cdc2) is required for mitosis in mammalian cells: microinjection of anti-p34 antibodies blocked cell division without affecting DNA synthesis; p34 localizes to the nucleus during interphase and associates with centrosomes during mitosis. |
Microinjection of antibodies into rat fibroblasts, immunofluorescence localization |
Cell |
High |
2541912
|
| 1990 |
Human p53 is phosphorylated by CDK1 (p60-cdc2 and cyclin B-cdc2) primarily at serine-315 in a cell cycle-dependent manner. |
In vitro kinase assay with purified p60-cdc2 and cyclin B-cdc2, phosphopeptide mapping, cell cycle fractionation |
Proceedings of the National Academy of Sciences of the United States of America |
High |
2141171
|
| 1991 |
CDK1 (cdc2 kinase) phosphorylates smooth muscle caldesmon in vitro, reducing its binding to F-actin; phosphorylation sites are located in the COOH-terminal actin/calmodulin-binding domain, suggesting cdc2-mediated caldesmon phosphorylation contributes to microfilament disassembly during mitosis. |
In vitro kinase assay with mitotic HeLa cdc2 kinase, tryptic mapping, F-actin cosedimentation assay |
The Journal of biological chemistry |
High |
2016282
|
| 1991 |
Cyclin A binds both CDK2 and CDC2 (CDK1), generating two distinct cyclin A kinase activities; anti-cyclin A antibody microinjection inhibits both DNA synthesis (S phase) and mitotic entry (G2/M), demonstrating CDK1-cyclin A has a role at two cell cycle points. |
Microinjection of anti-cyclin A antibodies, immunoprecipitation, in vitro kinase assay |
The EMBO journal |
High |
1312467
|
| 1991 |
Cyclin A and cyclin B1 are differentially localized: cyclin A is predominantly nuclear from S phase onwards and associates with a 33-kDa PSTAIRE-containing protein (CDK1/CDK2), while cyclin B1 accumulates in the cytoplasm and only enters the nucleus at the beginning of mitosis, where it associates with p34cdc2. |
Immunofluorescence, cell fractionation, immunoprecipitation |
The Journal of cell biology |
High |
1717476
|
| 1992 |
The retinoblastoma protein (pRB) physically associates with p34cdc2 or a closely related enzyme; the associated kinase activity phosphorylates pRB at most of its in vivo sites and is absent in G1 but appears in S phase, implicating CDK1 as a major regulator of pRB. |
Co-immunoprecipitation with anti-pRB antibodies, in vitro kinase assay on pRB substrate |
Molecular and cellular biology |
High |
1545827
|
| 1992 |
CDK1 (cdc2) transcription is cell cycle-regulated: high in S and G2, low in G1; the retinoblastoma protein (Rb) represses cdc2 transcription via E2F binding sites in the 5' flanking region. |
Nuclear run-on assays, CAT reporter gene assays, deletion analysis of promoter elements |
The EMBO journal |
High |
1582409
|
| 1992 |
CDK1 protein levels are maintained at a constant steady state through coordinated synthesis and degradation: transcription is activated at G1/S (12-fold), mRNA is rapidly degraded after mitosis, translation is shut off at mitotic onset, and >75% of new cdc2 complexes with cyclin. |
Metabolic labeling, pulse-chase, nuclear run-on, cell cycle synchronization, immunoprecipitation |
Proceedings of the National Academy of Sciences of the United States of America |
High |
1372997
|
| 1994 |
CDK1 (cdc2 kinase) phosphorylates vimentin at Ser55 upon mitotic entry; a phospho-specific monoclonal antibody (4A4) confirmed that all cytoplasmic vimentin Ser55 residues are phosphorylated at mitotic entry and dephosphorylated during cytokinesis; the degree of vimentin filament disassembly correlated with mitotic cdc2 kinase activity. |
Monoclonal antibody 4A4 (phospho-Ser55 specific), Western blot, immunofluorescence, immunoelectron microscopy, Mono-Q fractionation, in vitro kinase assay |
The Journal of biological chemistry |
High |
7983050
|
| 1995 |
Wee1 kinase phosphorylates CDK1 (Cdc2) at T14 in fission yeast; T14 phosphorylation plays an inhibitory role in Cdc2 activation and requires prior phosphorylation at Y15; Mik1 and Chk1 cannot drive T14 phosphorylation in vivo. |
In vivo phosphorylation analysis, chromosomal replacement with T14A/T14S cdc2 mutants, genetic epistasis |
Molecular biology of the cell |
High |
7626804
|
| 1995 |
HIV-1 Vpr arrests cells in G2 by preventing activation of the p34cdc2/cyclin B complex, maintaining CDK1 in a phosphorylated, inactive state; expression of constitutively active CDK1 relieves the Vpr-induced G2 arrest. |
Histone H1 kinase assay of immunoprecipitated CDK1/cyclin B complexes, constitutively active CDK1 rescue experiment, flow cytometry |
Journal of virology |
High |
7474080
|
| 1995 |
CDK1 (p34cdc2) phosphorylates human Eg5 kinesin at Thr-927 specifically during mitosis; mutation of Thr-927 to non-phosphorylatable residues prevents HsEg5 from binding to centrosomes, demonstrating that CDK1 phosphorylation controls spindle motor localization required for bipolar spindle formation. |
In vitro kinase assay with p34cdc2/cyclin B, site-directed mutagenesis (T927A), microinjection of anti-Eg5 antibodies, immunofluorescence |
Cell |
High |
8548803
|
| 1996 |
Fission yeast Cdc2 kinase interacts with Orp2 (ORC2-like protein), which is required for DNA replication; Cdc2 thus controls DNA replication initiation by acting directly at chromosomal origins. |
Genetic interaction, two-hybrid, co-immunoprecipitation, in vitro kinase assay |
Nature |
High |
8552194
|
| 1997 |
CDK1 inactivation is required for anaphase spindle dynamics and cytokinesis: expression of non-destructible cyclin B (preventing CDK1 inactivation) blocked chromosome decondensation, nuclear envelope reformation, and cytokinesis, and prevented F-actin/myosin II localization to the equator in normal rat kidney cells. |
Microinjection of non-destructible cyclin B mRNA into prometaphase cells, live imaging, rhodamine-tubulin injection, immunofluorescence |
The Journal of cell biology |
High |
9230080
|
| 1997 |
Myt1 kinase phosphorylates CDK1 at Thr14, maintaining CDK1 in an inactive state during the G2-to-M phase transition; Wee1 phosphorylates Tyr15. |
In vitro kinase assay, site-directed mutagenesis, biochemical characterization of purified Myt1 |
Progress in cell cycle research |
High |
9552418
|
| 1998 |
Fission yeast Cdc18 (Cdc6 homolog) interacts with Cdc2 in association with Cdc13 and Cig2 cyclins; Cdc2 phosphorylates Cdc18 in vitro and mutation of phosphorylation site T104A activates Cdc18 in a rereplication assay, establishing CDK1 as a negative regulator of replication re-initiation. |
Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis, rereplication assay, genetic suppression |
Molecular biology of the cell |
High |
9436991
|
| 1999 |
14-3-3σ sequesters CDK1 (cdc2) and cyclin B1 in the cytoplasm after DNA damage; loss of 14-3-3σ causes failure to maintain G2 arrest, allowing CDK1/cyclin B1 to enter the nucleus and leading to mitotic catastrophe. |
Somatic cell knockout of 14-3-3σ, immunofluorescence of cyclin B1/cdc2 localization, cell cycle analysis |
Nature |
High |
10524633
|
| 2000 |
CDK1 (cdc2) kinase is required for optimal expression of a subset of herpes simplex virus late (γ2) genes; cdc2 specifically phosphorylates the second exon of ICP0 in vitro, and a dominant-negative cdc2 suppresses US11 accumulation. |
Dominant-negative cdc2 expression, in vitro kinase assay on viral polypeptides, immunoblot |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
10995483
|
| 2001 |
Cdc2/cyclin B-cdc2 phosphorylates the dynein light intermediate chain (DLIC) at a conserved site; incubation of interphase membranes with cdc2-cyclinB1 kinase releases cytoplasmic dynein from the membrane, inhibiting organelle movement. |
In vitro kinase assay with purified Xenopus cdc2-GST-cyclinB1, mass spectrometry, membrane release assay |
The Journal of biological chemistry |
High |
11278950
|
| 2001 |
Drosophila cdc2 is required for maintaining asymmetric localization of apical complex components (Inscuteable, Partner of Inscuteable) during mitosis in neural progenitors; Cdc2/B-type cyclin complexes are necessary for proper asymmetric division but not for initiation of apical complex formation. |
Genetic attenuation of Drosophila cdc2 function, immunofluorescence of asymmetric components, clonal analysis |
Nature |
High |
11234018
|
| 2001 |
CDK1 (cdc2) forms stable molecular complexes with DNA topoisomerase II; this interaction stimulates topoisomerase II DNA binding and catalytic activity; the physical association is required for recruitment of cdc2 to the nucleus and is coupled to chromatin remodeling converting interphase nuclei into precondensation chromosomes. |
Co-immunoprecipitation, purified enzyme incubation with nuclei, pulse-field electrophoresis, chromatin remodeling assay |
FASEB journal |
Medium |
11511510
|
| 2002 |
CDK1 (p34cdc2) kinase activity is required for a survival checkpoint after microtubule stabilization: elevated CDK1 activity induces survivin expression, and pharmacologic/genetic ablation of CDK1 after microtubule stabilization causes massive p53-independent apoptosis and suppresses tumor growth in mice. |
Pharmacologic CDK1 inhibition, genetic ablation, in vivo tumor model, apoptosis assays |
Cancer cell |
Medium |
12150824
|
| 2003 |
CDK1 directly phosphorylates ~200 substrates in budding yeast identified by proteomic screening; several are phosphorylated in a CDK1-dependent manner in vivo, revealing a global regulatory strategy involving phosphorylation of other regulatory molecules and molecular machines. |
Analog-sensitive CDK1 allele with thiophosphate-ATP labeling in whole-cell extracts, proteomic library screen, in vivo validation |
Nature |
High |
14574415
|
| 2003 |
CDK1 (cdc2) phosphorylates Disabled-2 (Dab2) during mitosis at multiple sites; cdc2 co-immunoprecipitates with Dab2 and purified cdc2 phosphorylates Dab2 in vitro; Dab2 phosphorylation promotes association with Pin1 peptidylprolyl isomerase. |
Co-immunoprecipitation, in vitro kinase assay with purified cdc2, roscovitine inhibition |
Oncogene |
Medium |
12881709
|
| 2004 |
Drosophila Wee1 kinase regulates Cdk1 via phosphorylation of tyrosine 15, timing mitotic entry during syncytial blastoderm embryogenesis; loss of maternal dwee1 causes premature mitosis, spindle defects, chromosome condensation problems, and embryonic lethality. |
Genetic loss-of-function (maternal dwee1 mutants), in vitro kinase assay, immunofluorescence, Chk2 epistasis |
Current biology |
High |
15589158
|
| 2005 |
CDK1 (Cdc28) and Cks1 are recruited to multiple coding regions and are required for efficient transcription of a significant subset of genes in budding yeast; this transcriptional role requires Cdc28/Cks1-mediated proteasome recruitment but is independent of Cdc28 kinase activity. |
ChIP, transcriptomics, kinase-dead allele analysis, proteasome recruitment assay |
Molecular cell |
Medium |
15629725
|
| 2005 |
CDK1 phosphorylates vimentin at Ser55 (priming), creating a docking site for Plk1; Plk1 then phosphorylates vimentin at Ser82, which is required for vimentin filament segregation during mitosis; CDK1-Ser55 phosphorylation thus regulates mitotic vimentin phosphorylation via Plk1 recruitment. |
In vitro kinase assay, direct binding assay (Plk1-PBD to phospho-Ser55 vimentin), Plk1 depletion, mutational analysis (Ser55A, Ser82A), immunofluorescence |
The Journal of cell biology |
High |
16260496
|
| 2007 |
CDK1 has an unexpected role in controlling bud growth after bud emergence in budding yeast; G1 cyclin-Cdk1 complexes specifically phosphorylate multiple proteins associated with Cdc24 (GEF for Cdc42); a mutant Cdc24-associated protein that cannot undergo Cdk1-dependent phosphorylation causes bud growth defects. |
Proteomics (mass spectrometry), in vitro kinase assay, site-directed mutagenesis, genetic analysis |
Nature cell biology |
High |
17417630
|
| 2007 |
Mouse embryos lacking all interphase CDKs (Cdk2, Cdk3, Cdk4, Cdk6) can develop to midgestation with CDK1 binding all cyclins and phosphorylating pRb; embryos fail to develop past morula/blastocyst without Cdk1, establishing CDK1 as the only essential cell cycle CDK. |
Compound CDK knockout mice, MEF proliferation assays, pRb phosphorylation analysis, E2F target gene expression |
Nature |
High |
17700700
|
| 2007 |
CDK1 (cdc2) phosphorylation of caldesmon regulates Schwann cell migration; Cdc2 expression increases in injury-preconditioned Schwann cells, and dominant-negative Cdc2 or dominant-negative caldesmon reduces migration; wild-type Cdc2 overexpression promotes distal Schwann cell migration in sciatic nerve. |
Dominant-negative and wild-type Cdc2 adenoviral transduction, migration assays, roscovitine inhibition, in vivo sciatic nerve implantation |
Journal of cell science |
Medium |
17200138
|
| 2008 |
CDK1 directly regulates vacuole inheritance in budding yeast by phosphorylating the myosin V adaptor Vac17; phosphorylation of Vac17 parallels cell cycle-dependent vacuole movement, and non-phosphorylatable Vac17 shows decreased interaction with Myo2 and impaired vacuole inheritance. |
In vitro CDK1 kinase assay, site-directed mutagenesis of Cdk1 phosphorylation sites in Vac17, co-immunoprecipitation (Vac17-Myo2), vacuole inheritance assays |
Developmental cell |
High |
18804442
|
| 2010 |
CyclinB1-CDK1 is inactive in G2 and activated at a defined time before nuclear envelope breakdown; different levels of CyclinB1-CDK1 kinase activity trigger different mitotic events, coordinating the mitotic entry program. |
FRET biosensor specific for CyclinB1-Cdk1 in living human cells, cell synchronization |
Developmental cell |
High |
20412769
|
| 2010 |
CDK1 and CDK2 phosphorylation sites in mitotic cells show near-complete occupancy (>full phosphorylation) for up-regulated sites, particularly for nuclear proteins and proteins regulating metabolic processes, as determined by quantitative phosphoproteomics. |
High-resolution mass spectrometry-based phosphoproteomics with stoichiometry measurements across cell cycle stages |
Science signaling |
High |
20068231
|
| 2011 |
CDK1 phosphorylates Sororin during mitosis; phosphorylation of Cdk1 sites causes Sororin release from chromatin and cohesin, thereby reducing sister chromatid cohesion; hypophosphorylated Sororin increases cohesion and premature mitotic exit caused by sororin knockdown is abolished by Aurora kinase inhibition. |
Site-directed mutagenesis of CDK1 phosphorylation sites, DNA-cellulose pulldown, co-immunoprecipitation, ZM447439 (Aurora kinase inhibitor) treatment, flow cytometry |
Journal of cell science |
High |
21878504
|
| 2011 |
CDK1-phosphorylated CUEDC2 promotes spindle checkpoint inactivation: Cdk1 phosphorylates CUEDC2 during mitosis; phospho-CUEDC2 binds Cdc20 and promotes Mad2 release from APC/C-Cdc20, activating APC/C; CUEDC2 overexpression causes premature APC/C activation, chromosome missegregation, and aneuploidy. |
In vitro kinase assay, co-immunoprecipitation, siRNA depletion, APC/C ubiquitination assay, chromosome segregation analysis |
Nature cell biology |
High |
21743465
|
| 2012 |
CDK1/cyclin B phosphorylates Ubc9 (SUMO E2 conjugating enzyme) at serine 71, enhancing its SUMOylation activity and increasing Ubc9-SUMO1 thioester conjugate levels; CDK2/cyclin E, ERK1, ERK2, PKA, and JNK2 do not show this effect. |
In vitro kinase assay with multiple kinases, Ubc9 SUMOylation assay, site-directed mutagenesis (S71A), thioester conjugate detection |
PloS one |
High |
22509284
|
| 2013 |
Aurora B and CDK1 cooperate to phosphorylate Sororin, destabilizing interactions between Sororin and Pds5, thereby releasing acetylated cohesin from chromosome arms in prophase/prometaphase; at centromeres, Sgo1-PP2A antagonizes Aurora B and CDK1 by dephosphorylating Sororin, maintaining cohesion until metaphase. |
In vitro kinase assay, co-immunoprecipitation (Sororin-Pds5), phospho-specific antibodies, PP2A dephosphorylation assay, RNAi depletion |
Proceedings of the National Academy of Sciences of the United States of America |
High |
23901111
|
| 2013 |
Cdk1/Cdc5 pathway activates Mus81-Mms4 via phosphorylation to resolve DNA damage tolerance recombination intermediates before anaphase; premature activation of the Cdk1/Cdc5/Mus81 pathway via phosphomimetic Mms4 variants or S-phase checkpoint-deficient backgrounds causes crossover-associated chromosome translocations. |
Phosphomimetic mutations (Mms4), checkpoint mutant analysis, genetic epistasis, two-dimensional gel electrophoresis for intermediates |
The EMBO journal |
High |
23531881
|
| 2015 |
CDK1 phosphorylates SIRT3 at Thr150/Ser159, enhancing its deacetylase activity in mitochondria; radiation induces CDK1 and SIRT3 relocalization to mitochondria; Thr150Ala/Ser159Ala SIRT3 mutant shows reduced mitochondrial protein deacetylation, MnSOD activity, and ATP generation, and reduces tumor radioresistance. |
In vitro kinase assay (cyclin B1-CDK1 on SIRT3), site-directed mutagenesis (T150A/S159A), mitochondrial fractionation, MnSOD activity assay, clonogenic assay, in vivo xenograft |
Molecular cancer therapeutics |
High |
26141949
|
| 2015 |
CDK1 relocates to mitochondria upon radiation and phosphorylates complex I subunits, boosting mitochondrial ATP generation; cells expressing kinase-deficient mitochondrially-targeted CDK1 or phosphorylation-deficient complex I subunits show reduced mitochondrial ATP and impaired nuclear DNA repair. |
Mitochondrial fractionation, CDK1 phosphorylation-deficient mutant complex I subunits, kinase-dead mitochondrially-targeted CDK1, oxygen consumption measurement, ATP generation assay, DNA repair (γH2AX) assay |
Cell reports |
High |
26670043
|
| 2015 |
CDK1 phosphorylation of RepoMan differentially regulates associated phosphatases PP1 and PP2A-B56: CDK1 phosphorylation reduces PP1 binding but facilitates PP2A-B56 recruitment; CDK1 inactivation in early anaphase reverses this switch, allowing PP1-RepoMan to accumulate, inactivate Aurora B, and initiate nuclear envelope reassembly. |
In vitro CDK1 kinase assay on RepoMan, co-immunoprecipitation (PP1/PP2A-B56 with RepoMan), phospho-mutant analysis, live cell imaging of mitotic exit |
Nature communications |
High |
26674376
|
| 2016 |
CDK1 in complex with cyclin A2 promotes adhesion complex and actin cytoskeleton organization during interphase (G1→S transition increases adhesion complex area); a decrease in adhesion complex area in G2 is triggered by inhibitory phosphorylation of CDK1-cyclin complexes requiring elevated cyclin B1, establishing CDK1 inactivation as the trigger for adhesion remodeling before mitosis. |
Cell synchronization, CDK1 inhibition (RO-3306), cyclin B1 siRNA, total internal reflection fluorescence microscopy of adhesion complexes, live imaging |
The Journal of cell biology |
High |
29930204
|
| 2016 |
CDK1 (metaphase Cdk1) phosphorylates fimbrin at Thr103 in vitro and in vivo; conformational simulations suggest phosphorylation stabilizes fimbrin's N-terminal domain; phospho-fimbrin modulates actin filament binding to regulate actin cable assembly and stability in budding yeast. |
In vitro kinase assay (metaphase cyclin-Cdk1 complex), mass spectrometry identification of Thr103 phosphorylation, T103A/T103D mutants, actin cable imaging, molecular dynamics simulation |
Nature communications |
High |
27068241
|
| 2016 |
CDK1 phosphorylates Ajuba at Ser119 and Ser175 during G2/M phase; mitotic phosphorylation of Ajuba controls cell cycle regulator expression, promotes cell proliferation and anchorage-independent growth in vitro, and promotes tumorigenesis in vivo, independent of Hippo pathway effects. |
In vitro CDK1 kinase assay, in vivo phosphorylation during cell cycle, site-directed mutagenesis (S119A/S175A), proliferation assays, xenograft tumor assay |
The Journal of biological chemistry |
High |
27226586
|
| 2017 |
CDK1 coordinates nuclear envelope disassembly/reassembly with the cell cycle: CDK1 activity controls Lamin A/C targeting to chromatin (clock-based model), while PLK1 negatively regulates NPC assembly and is required for NPC disassembly at mitotic entry. |
CDK1 and PLK1 inhibition, immunofluorescence of Lamin A/C and NPC components, live-cell imaging |
Oncotarget |
Medium |
29487689
|
| 2018 |
Premature activation of CDK1 (CDK1AF knockin with T14A/Y15F) causes S phase arrest, γH2AX formation, premature activation of MUS81-SLX4 endonuclease complexes, and untimely chromosome condensation/nuclear lamina disassembly, leading to embryonic lethality; CDK1AF MEFs show chromosomal fragmentation partly independent of CDK2. |
Cdk1AF knockin mice, MEF analysis, γH2AX immunofluorescence, MUS81-SLX4 inhibition, chromosome condensation assay |
Oncogene |
High |
30190546
|
| 2018 |
DNA replication restricts CDK1 and PLK1 activation: human cells unable to initiate DNA replication prematurely enter mitosis, and blocking DNA replication licensing/firing causes prompt CDK1 and PLK1 activation in S phase; CDK1 activation during replication causes severe replication stress. |
Double-degron system for protein depletion, CDK1/PLK1 activity reporters, DNA replication inhibitors, kinase inhibitors (CHK1, p38) |
Molecular cell |
High |
30008317
|
| 2018 |
CDK1 interacts with the pluripotency transcription factor Sox2 and phosphorylates it, promoting Sox2 nuclear localization and transcriptional activity; CDK1 kinase activity is required for CDK1-driven tumor-initiating capacity in melanoma. |
Proteomic analysis (CDK1 interactome), co-immunoprecipitation (CDK1-Sox2), Sox2 phosphorylation analysis, CDK1 overexpression/inhibition, Sox2 knockout in CDK1-OE cells, in vitro/in vivo tumor-initiating assays |
Cancer research |
Medium |
30297536
|
| 2019 |
CDK1 primes BUB1 and CENP-U for PLK1 recruitment to kinetochores by phosphorylating docking sites; BUB1 and CENP-U are the main PLK1 kinetochore receptors in mitosis, and CDK1-dependent priming creates a positive feedback loop for MPS1 recruitment and sustained spindle checkpoint arrest. |
Ectopic localization assay, in vitro reconstitution with purified proteins, kinetochore localization studies, co-immunoprecipitation, phospho-mutant analysis |
Molecular cell |
High |
33248027
|
| 2019 |
MAD1 recruits CDK1-CCNB1 to unattached kinetochores in an MPS1-dependent manner via interactions with the first 100 amino acids of MAD1; CDK1-CCNB1 at kinetochores phosphorylates MPS1 and creates a positive feedback loop for spindle checkpoint signaling. |
Proteomic analysis of CCNB1 complexes, co-immunoprecipitation, kinetochore localization analysis (with/without microtubule attachment), phospho-MPS1 assays, MAD1 truncation analysis |
The Journal of cell biology |
High |
30674583
|
| 2019 |
CDK1 and CDK2 phosphorylate NICD (Notch intracellular domain) to regulate its stability and promote its degradation; inhibiting CDK1 or CDK2 increases NICD levels in vitro and in vivo, delays segmentation clock gene oscillations, and increases somite size. |
In vitro CDK1 kinase assay on NICD, CDK1/CDK2 inhibitors in cell and embryo models, NICD phospho-mutant analysis, somite size measurement |
EMBO reports |
High |
31267714
|
| 2020 |
CDK1-cyclin B complex phosphorylates cGAS at S305 (human) or S291 (mouse) upon mitotic entry, inhibiting cGAS ability to synthesize cGAMP in response to self-DNA; PP1 phosphatase dephosphorylates cGAS upon mitotic exit to restore DNA sensing capacity. |
In vitro kinase assay (CDK1-cyclin B on cGAS), site-directed mutagenesis (S305A), cGAMP synthesis assay, cell imaging of cGAS localization during mitosis, PP1 dephosphorylation assay |
Cell discovery |
High |
32351706
|
| 2020 |
CDK1 is a positive regulator of global translation (extramitotic function): CDK1 controls eIF2α, 4EBP, and S6K1 signaling pathways; CDK1 has a particularly strong effect on 5'TOP mRNA translation through LARP1 phosphorylation. |
Kinase/phosphatase screen, stress granule formation assay, cell synchronization, Ribo-Seq, LARP1 phosphorylation analysis by mass spectrometry |
The Journal of cell biology |
High |
32040547
|
| 2021 |
USP7 limits CDK1 activity throughout the cell cycle by supporting active PP2A localization in the cytoplasm; USP7 inhibition causes widespread CDK1 activation and increased phosphorylation of CDK1 targets leading to DNA damage and cell toxicity; this toxicity is alleviated by lowering CDK1 activity or activating PP2A. |
USP7 inhibitors, phosphoproteomics (CDK1 target phosphorylation), PP2A co-immunoprecipitation with USP7, CDK1 activity rescue experiments |
The EMBO journal |
High |
33856059
|
| 2022 |
CDK1 activity is compartmentalized during mitosis: a spindle-associated CDK1 fraction escapes Cdc25 activation and remains phosphorylated (inactive, i-Cdk1) through association with Wee1 while excluding Cdc25; this local CDK1 inhibition is required for spindle microtubule growth and spindle assembly. |
Immunofluorescence of phospho-CDK1 (i-Cdk1) on spindle, biochemical fractionation, live-cell imaging, Wee1/Cdc25 co-localization on spindle, loss/restoration of i-Cdk1 with defined spindle assembly phenotype |
Cell reports |
High |
35081344
|
| 2022 |
S6K1 phosphorylates CDK1 at serine 39, causing G2/M cell cycle arrest and enabling homologous recombination DNA repair; this represents a direct regulatory input from mTORC1-S6K1 signaling onto CDK1 activity. |
In vitro kinase assay (S6K1 on CDK1), site-directed mutagenesis (S39A), cell cycle analysis, DNA repair assays (HR reporter) |
eLife |
High |
36189922
|
| 2023 |
CDK1 phosphorylates USP29, activating its deubiquitinase activity toward TWIST1; CDK1-mediated USP29 phosphorylation is required for TWIST1 stabilization and TWIST1-driven EMT and cancer stem cell functions in triple-negative breast cancer. |
In vitro CDK1 kinase assay on USP29, deubiquitinase activity assay, co-immunoprecipitation (CDK1-USP29, USP29-TWIST1), CDK1 inhibition/knockout, phospho-mutant analysis |
Advanced science |
High |
36782089
|
| 2025 |
PSMD12 interacts with CDK1, preventing its ubiquitin-mediated degradation through deubiquitination, thereby stabilizing CDK1 protein and promoting HCC cell cycle progression and cancer progression. |
Co-immunoprecipitation (PSMD12-CDK1), ubiquitination assay, PSMD12 knockdown/overexpression, cell proliferation and cycle analysis |
Frontiers in immunology |
Medium |
40534847
|