Affinage

WEE1

Wee1-like protein kinase · UniProt P30291

Length
646 aa
Mass
71.6 kDa
Annotated
2026-06-11
100 papers in source corpus 28 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

WEE1 is a nuclear protein kinase that restrains entry into mitosis by phosphorylating the cyclin-dependent kinase CDK1 (p34cdc2) exclusively at Tyr15, thereby holding cells in interphase until division is appropriate (PMID:8428596, PMID:1840647). Although it functions biochemically as a tyrosine kinase, its catalytic domain adopts a fold most closely resembling serine/threonine kinases, with a Wee1-specific activation segment and a glycine-rich loop substitution that together dictate Tyr15 substrate specificity (PMID:15837193). This activity is conserved across eukaryotes: human WEE1 complements fission yeast wee1 mutants, and orthologs time mitotic entry in yeast and Drosophila embryos (PMID:1840647, PMID:15589158). WEE1 enforces cell-cycle checkpoints—loss of yeast Wee1 abolishes radiation-induced mitotic delay, and WEE1A is rate-limiting for DNA-damage checkpoint arrest in human cells (PMID:1549179, PMID:17431037). WEE1 abundance and activity are tightly regulated: at mitotic entry, Plk1 phosphorylation at Ser53 and CDK phosphorylation at Ser123 generate phosphodegrons recognized by the SCF(β-TrCP) ubiquitin ligase, with CK2, CK1δ, and a polo-box-binding motif reinforcing degron formation, driving WEE1 ubiquitination and proteasomal degradation (PMID:15070733, PMID:16085715, PMID:24817118). Conversely, in response to DNA damage CHK1-dependent phosphorylation at Ser642 primes GCN5-mediated acetylation at Lys177 to activate WEE1, an activation reversed by SIRT1 deacetylation (PMID:36635566, PMID:10769204). Beyond mitotic gating, WEE1 suppresses CDK2 activity to protect stalled replication forks from DNA2-mediated nascent-DNA degradation and to restrain origin firing (PMID:35045293, PMID:31712441), and it phosphorylates histone H2B at Tyr37 to suppress histone gene transcription, coupling histone synthesis to cell-cycle progression (PMID:23537585).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1991 High

    Established that the human gene encodes a bona fide mitotic inhibitor by showing functional conservation with the yeast cell-size/cell-cycle regulator.

    Evidence Transcomplementation of S. pombe wee1 mutants and overexpression-induced G2/M delay

    PMID:1840647

    Open questions at the time
    • Did not define the molecular substrate or biochemical activity
    • Conservation shown genetically, not biochemically
  2. 1992 High

    Placed Wee1 within the DNA damage response by showing its kinase activity is required to delay mitosis after irradiation, linking it to checkpoint control.

    Evidence Genetic epistasis with wee1 mutants under gamma-irradiation in fission yeast

    PMID:1549179

    Open questions at the time
    • Upstream signal connecting damage to Wee1 not defined
    • Substrate of the checkpoint-dependent activity not identified here
  3. 1993 High

    Defined the core biochemical reaction—Tyr15-specific phosphorylation of CDK1—and proved catalytic activity is essential for mitotic inhibition.

    Evidence In vitro kinase assay with purified human WEE1, catalytic Lys114 mutagenesis, overexpression in HeLa

    PMID:8428596

    Open questions at the time
    • Did not address regulation of WEE1 itself
    • Tyr15 selectivity structural basis unknown at this stage
  4. 1993 High

    Identified the first direct upstream regulator, showing a kinase (Nim1) inactivates Wee1 to promote mitotic entry.

    Evidence In vitro kinase assay with purified Nim1 and Wee1; in vivo phosphorylation analysis in nim1 mutants

    PMID:8515817 PMID:8515818

    Open questions at the time
    • Phosphosites on Wee1 not mapped
    • Human ortholog of this regulation not established
  5. 1995 High

    Showed WEE1 is the dominant CDK1-Tyr15 kinase in human cells and is inactivated by phosphorylation during M phase, and that it undergoes cell-cycle-regulated nuclear-to-cytoplasmic redistribution.

    Evidence Antibody depletion and in vitro kinase assays of HeLa lysates; immunofluorescence across the cell cycle with microtubule depolymerization

    PMID:7673359 PMID:7774574

    Open questions at the time
    • Identity of the M-phase inactivating kinase(s) not yet defined
    • Functional consequence of midbody association unclear
  6. 2000 High

    Connected the DNA-damage checkpoint to Wee1 regulation in metazoan-relevant terms by showing Chk1 directly phosphorylates Wee1 and that checkpoint arrest requires coordinate Wee1 up- and Cdc25 down-regulation.

    Evidence Genetic epistasis (wee1/cdc25 double mutants), in vitro Chk1 kinase assay, overexpression and immunoblotting in S. pombe

    PMID:10769204

    Open questions at the time
    • Chk1 phosphosites on Wee1 not mapped here
    • Mechanism linking phosphorylation to activity change undefined
  7. 2002 Medium

    Revealed that distinct Wee1 isoforms carry isoform-specific regulatory domains tuning inhibitory strength and stability, explaining differential CDK1 control.

    Evidence Ectopic expression, Cdc2 activity assays and domain-deletion analysis in Xenopus oocytes/embryos

    PMID:12006499

    Open questions at the time
    • Relevance of isoform distinctions to human somatic cells unclear
    • Single-organism domain dissection
  8. 2004 High

    Defined the degradation arm of WEE1 control, identifying SCF(β-TrCP) as the ligase and Plk1/CDK-generated phosphodegrons (Ser53, Ser123) that trigger mitotic-entry destruction.

    Evidence Co-IP, in vitro ubiquitination, phosphodegron mutagenesis, siRNA, HeLa synchronization

    PMID:15070733

    Open questions at the time
    • Did not resolve how multiple kinases are temporally ordered
    • Contribution of additional priming kinases not addressed here
  9. 2005 High

    Resolved the structural basis for tyrosine specificity and detailed the multi-kinase logic that builds the β-TrCP degron, including CK2 priming and polo-box motif creation.

    Evidence 1.8 Å crystal structure of WEE1A catalytic domain; in vitro binding, mutagenesis, CK2 inhibition and siRNA

    PMID:15837193 PMID:16085715

    Open questions at the time
    • Full-length, regulatory-domain-containing structure absent
    • In-cell stoichiometry of degron phosphorylation events not quantified
  10. 2007 High

    Demonstrated WEE1A is rate-limiting for checkpoint enforcement in a human cell context, with low expression causing checkpoint failure rescuable by re-expression.

    Evidence Gamma-irradiation of primary HPECs, CDK2 kinase assays, ectopic WEE1A rescue

    PMID:17431037

    Open questions at the time
    • Generality across cell types not established
    • Mechanism of low WEE1 expression in HPECs unknown
  11. 2013 Medium

    Expanded WEE1 function beyond CDK gating by identifying histone H2B Tyr37 as a chromatin substrate coupling histone transcription to cell-cycle progression.

    Evidence Biochemical analysis of H2B Tyr37 phosphorylation and histone gene transcription after WEE1 manipulation

    PMID:23537585

    Open questions at the time
    • Methodological detail limited
    • Interplay with canonical CDK1 role not integrated
  12. 2018 High

    Provided a spatial, size-dependent mechanism for Wee1 inhibition, showing Cdr2 cortical nodes recruit Wee1 in bursts scaling with cell size.

    Evidence TIRF live imaging, biochemical fractionation, kinase-dead and pom1 genetics in S. pombe

    PMID:29514920

    Open questions at the time
    • Node-based regulation is yeast-specific; human equivalent unknown
    • Direct biochemical inactivation at nodes not fully resolved
  13. 2019 Medium

    Established WEE1 as a guardian of DNA replication, showing it suppresses CDK1/CDK2 to sustain ATR/Chk1 signaling, restrain origin firing, and protect forks under replicative stress.

    Evidence Pharmacological inhibition (MK-1775/AZD1775), siRNA, phosphoproteomics, immunoblotting of Claspin/CtIP/RIF1

    PMID:25965828 PMID:31712441

    Open questions at the time
    • Reliance on single inhibitor for several conclusions
    • Direct vs indirect effects on each effector not fully separated
  14. 2022 Medium

    Pinpointed the fork-protection mechanism, identifying DNA2 as the degrading nuclease unleashed by WEE1 inhibition and distinguishing WEE1 from other CDK suppressors.

    Evidence DNA fiber assays with WEE1, DNA2 and CDK2 inhibition/knockdown plus immunofluorescence

    PMID:35045293

    Open questions at the time
    • Single-lab finding
    • Molecular link from CDK2 activity to DNA2 recruitment unresolved
  15. 2023 High

    Defined an acetylation switch governing WEE1 activity, with CHK1-primed GCN5 acetylation at Lys177 activating the kinase and SIRT1 deacetylation inactivating it, also explaining inhibitor resistance.

    Evidence In vitro kinase, acetylation/deacetylation assays, Ser642/Lys177 mutagenesis, Co-IP, cancer cell studies

    PMID:36635566

    Open questions at the time
    • Structural picture of the inhibitory segment displacement incomplete
    • Interplay between acetylation activation and β-TrCP degradation not integrated
  16. 2024 High

    Provided a structural basis for targeted WEE1 degradation by defining a CRBN-DDB1-WEE1 ternary complex with molecular glue degraders, rationalizing kinase selectivity.

    Evidence Crystal structure of CRBN-DDB1-WEE1-compound complex with degradation assays

    PMID:39499896

    Open questions at the time
    • Therapeutic in vivo efficacy not addressed here
    • Neosubstrate surface relative to native regulation unmapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how WEE1's multiple regulatory layers—Tyr15 gating, phosphodegron-driven degradation, CHK1-primed acetylation activation, and its non-CDK chromatin and replication-fork functions—are integrated in a single cell to time both mitotic entry and replication protection.
  • No unified quantitative model linking acetylation, phosphorylation and degradation
  • Mammalian spatial/size-control mechanism for WEE1 inhibition unknown
  • Full-length WEE1 structure with regulatory domains lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0016740 transferase activity 3 GO:0140657 ATP-dependent activity 1
Localization
GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-73894 DNA Repair 3 R-HSA-69306 DNA Replication 2 R-HSA-4839726 Chromatin organization 1
Partners
BTRCCDK1CDK2CHK1CSNK1DGCN5PLK1SIRT1
Complex memberships
CRBN-DDB1 ternary complex (induced)SCF(β-TrCP) substrate

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 Human WEE1 kinase phosphorylates p34cdc2 exclusively on Tyr15 (not Thr14) in vitro, and mutation of the catalytic lysine (Lys114) abolishes both in vitro kinase activity and in vivo mitotic inhibitor function, establishing WEE1 as a Tyr15-specific kinase that inhibits mitosis by directly phosphorylating p34cdc2. In vitro kinase assay with purified human WEE1, active-site mutagenesis (Lys114), overexpression in HeLa cells The EMBO journal High 8428596
1991 Human WEE1 (WEE1Hu) functionally complements fission yeast wee1 mutations and causes G2/M delay when overexpressed in fission yeast, establishing functional conservation of the mitotic inhibitor role. Transcomplementation of yeast wee1 mutant; overexpression in S. pombe Nature High 1840647
1993 Fission yeast Nim1 kinase directly phosphorylates and inactivates Wee1 in vitro, inhibiting its ability to phosphorylate Cdc2 on Tyr15; this phosphorylation of Wee1 by Nim1 promotes mitotic entry. In vitro kinase assay with purified Nim1 and Wee1; in vivo phosphorylation state analysis in nim1-overexpressing and nim1-null yeast Nature High 8515817 8515818
1995 Human WEE1 (~94 kDa) accounts for most of the CDC2 Tyr15-phosphorylating activity in HeLa cell lysates (shown by antibody depletion), is suppressed during M phase, and its inhibitory state during M phase requires protein phosphorylation (demonstrated by re-activation upon removal of phosphatase inhibitors). Antibody depletion from HeLa cell lysates; in vitro kinase assay; cell synchronization with/without phosphatase inhibitors The EMBO journal High 7774574
1995 Human WEE1 localizes almost exclusively to the nucleus during interphase, relocates to the cytoplasm at mitotic entry, and associates with the midbody/midbody bridges at the end of mitosis in a microtubule-dependent manner, indicating cell cycle-regulated subcellular redistribution. Immunofluorescence microscopy of HeLa and IMR90 cells throughout the cell cycle; microtubule depolymerization experiments Journal of cell science Medium 7673359
2004 SCF(β-TrCP1/2) is the E3 ubiquitin ligase responsible for WEE1A ubiquitination and degradation at mitotic entry. Plk1 phosphorylates WEE1A at Ser53 and Cdc2 phosphorylates it at Ser123, creating unconventional phosphodegrons recognized by β-TrCP; these two phosphorylations cooperatively stimulate WEE1A ubiquitination. Depletion of β-TrCP or mutation of S53/S123 stabilizes WEE1A and delays mitotic onset. Co-immunoprecipitation, in vitro ubiquitination assay, site-directed mutagenesis, siRNA depletion, HeLa cell synchronization Proceedings of the National Academy of Sciences of the United States of America High 15070733
2005 CDK-mediated phosphorylation of WEE1A at Ser123 promotes β-TrCP binding through three independent mechanisms: direct interaction of pSer123 with WD40 repeats of β-TrCP; creation of a polo-box domain-binding motif (SpSP) that accelerates Plk1-mediated phosphorylation of Ser53; and priming of CK2-dependent phosphorylation of Ser121, generating a second β-TrCP-binding site. CK1δ also contributes to WEE1 degradation. In vitro binding assays, mutagenesis, CK2 inhibitor treatment, siRNA, cell synchronization Proceedings of the National Academy of Sciences of the United States of America High 16085715
2005 Crystal structure of the catalytic domain of human somatic WEE1 (WEE1A) at 1.8 Å resolution reveals that despite being functionally a tyrosine kinase, it most closely resembles serine/threonine kinases (Chk1, cAMP kinases) in sequence and structure; the activation segment has Wee1-specific features maintaining an active conformation, and a glycine-rich loop substitution helps determine substrate specificity for Tyr15. X-ray crystallography (1.8 Å resolution) with active-site inhibitor complex Structure High 15837193
1992 In fission yeast, functional wee1 protein kinase is required for radiation-induced mitotic delay, establishing Wee1 as a necessary component of the DNA damage checkpoint that delays mitosis in response to gamma-irradiation. Genetic epistasis using wee1 mutants exposed to gamma-irradiation; cell cycle progression analysis Nature High 1549179
2000 In fission yeast, the G2 DNA damage checkpoint simultaneously upregulates Wee1p and downregulates Cdc25p; inactivation of both wee1+ and cdc25+ is required to abolish checkpoint arrest. Chk1p directly phosphorylates Wee1p in vitro and its overexpression causes wee1+-dependent G2 arrest with Wee1p hyperphosphorylation. A transient increase in Wee1p levels is induced by G2 DNA damage checkpoint activation. Genetic epistasis (wee1 and cdc25 double mutants), in vitro Chk1 kinase assay with Wee1 as substrate, overexpression studies, immunoblotting Journal of cell science High 10769204
2004 Drosophila Wee1 (dWee1) phosphorylates Cdk1 at tyrosine 15 and times mitotic entry during syncytial blastoderm embryogenesis; loss of maternal dwee1 causes premature mitotic entry, spindle defects, chromosome condensation problems, and Chk2-dependent developmental arrest. Genetic loss-of-function (maternal dwee1 mutants), phospho-Tyr15 immunoblot, live imaging in Drosophila embryos Current biology High 15589158
2013 WEE1 phosphorylates histone H2B at Tyr37 in nucleosomes upstream of the histone gene cluster, suppressing histone transcription in late S phase, establishing WEE1 as an epigenetic modifier with a role in coordinating histone synthesis with cell cycle progression. Biochemical analysis of H2B Tyr37 phosphorylation, histone gene transcription assays following WEE1 manipulation Trends in genetics Medium 23537585
2014 CK1δ (casein kinase 1δ) promotes WEE1 protein degradation; pharmacological inhibition, siRNA knockdown, or conditional deletion of CK1δ reduces WEE1 turnover, arresting HeLa cell proliferation. Reporter assay (K328M-Wee1-luciferase), kinase-directed chemical library screen, CK1δ inhibitors, siRNA knockdown, conditional deletion The Journal of biological chemistry Medium 24817118
2010 Wee1/Swe1 phosphorylates Hsp90 at a conserved tyrosine residue; this phosphorylation is important for Wee1/Swe1 association with Hsp90 and for Wee1/Swe1 stability. Non-phosphorylatable yHsp90-Y24F yeast, like swe1Δ cells, undergo premature nuclear division insensitive to G2/M checkpoint arrest. Yeast genetic analysis (swe1Δ, hsp90-Y24F mutants), cell cycle analysis, immunoprecipitation, geldanamycin sensitivity assays Cell cycle Medium 20519952
2019 WEE1 inhibition suppresses CDK1 and CDK2 kinase activities, and WEE1 activity is required to sustain ATR/Chk1 signaling under replicative stress; mechanistically, WEE1 inhibition activates Cdk1/2 and Plk1, which reduce Claspin and CtIP levels to impair ATR/Chk1 signaling. Pharmacological inhibition (MK-1775, ATR and Chk1 inhibitors), siRNA knockdown, immunoblotting for Claspin and CtIP, CDK activity assays Oncotarget Medium 25965828
2019 WEE1 inhibitor AZD1775 induces CDK1-dependent RIF1 phosphorylation and CDK2/CDC7-dependent replicative helicase activation, demonstrating that WEE1 suppresses CDK1 and CDK2 to regulate origin firing at the G1/S transition. Pharmacological inhibition (AZD1775), phosphoproteomics, immunoblotting, flow cytometry in unperturbed G1 and S-phase cells Proceedings of the National Academy of Sciences Medium 31712441
2022 WEE1 activity guards against nascent DNA degradation at stalled replication forks by suppressing CDK2 activity; DNA2 is identified as the nuclease responsible for excessive fork degradation in WEE1-inhibited cells, and WEE1's fork protection role is unique among CDK suppressors (CHK1 and p21 do not promote fork protection as WEE1 does). DNA fiber assay, WEE1 inhibitor (AZD1775), DNA2 inhibitor/knockdown, CDK2 inhibition, immunofluorescence Cell reports Medium 35045293
2023 Upon DNA damage, CHK1-dependent phosphorylation of WEE1 at Ser642 primes GCN5-mediated acetylation at Lys177, causing dissociation of an inhibitory segment from the kinase domain and activating WEE1. SIRT1 deacetylates WEE1 at Lys177, maintaining it in an inactive state; SIRT1 deficiency leads to WEE1 hyperacetylation and activation, conferring resistance to WEE1 inhibitors. In vitro kinase assays, acetylation/deacetylation biochemical assays, site-directed mutagenesis, Co-IP, immunoblotting, cancer cell line functional studies Nature chemical biology High 36635566
2018 In fission yeast, Cdr2 cortical nodes recruit Wee1 in short bursts in a manner requiring Cdr2 kinase activity and the non-catalytic N-terminus of Wee1; Wee1 localization bursts at nodes increase 20-fold as cells double in size during G2, partially suppressed by the Cdr2 inhibitor Pom1 in small cells, establishing a size-dependent mechanism for Wee1 inhibition at nodes by Cdr1 and Cdr2 kinases. TIRF microscopy live-cell imaging, biochemical fractionation, kinase-dead mutant analysis, genetic epistasis (pom1 mutants) The Journal of cell biology High 29514920
2017 In fission yeast, both Wee1 and Cdc25 undergo cell cycle-dependent phosphorylation changes that are dependent on PP2A associated with regulatory subunit Pab1, indicating a conserved PP2A-dependent mechanism for controlling Wee1 across eukaryotes. Phosphorylation state analysis by SDS-PAGE, genetic analysis in S. pombe PP2A mutants Cell cycle Medium 28103117
2007 Human prostate epithelial cells (HPECs) express low levels of WEE1A and fail to enforce DNA damage checkpoint arrest due to a lack of inhibitory CDK phosphorylation; ectopic WEE1A expression rescues checkpoint arrest in gamma-irradiated HPECs, establishing WEE1A as rate-limiting for checkpoint enforcement in this cell type. Gamma-irradiation of primary HPECs and ex vivo prostate tissue, CDK2 kinase assay, ectopic WEE1A expression rescue, immunoblotting, flow cytometry Proceedings of the National Academy of Sciences High 17431037
2024 Molecular glue degraders (WEE1-targeting glutarimide-containing compounds) form a ternary complex with CRBN-DDB1 and WEE1; crystal structure of the hit compound with CRBN-DDB1-WEE1 defines the protein-protein interface and rationalizes kinase selectivity for WEE1 degradation. Crystal structure of CRBN-DDB1-WEE1-compound ternary complex, multicomponent combinatorial library synthesis and screening, degradation assays Journal of the American Chemical Society High 39499896
2021 WEE1 inhibition activates the STING-TBK1-IRF3 pathway, increases type I interferons and pro-inflammatory chemokines, and concomitantly activates STAT1, increasing IFN-γ and PD-L1 expression in SCLC models, demonstrating a cell-autonomous immune-stimulating mechanism. WEE1 inhibitor (AZD1775) treatment of SCLC cell lines, pathway activation immunoblotting, immunocompetent mouse models, cytokine measurement, CD8+ T cell analysis Cell reports Medium 35584676
2021 WEE1 inhibition up-regulates endogenous retroviral elements (ERVs) by relieving SETDB1/H3K9me3 repression through downregulation of FOXM1; ERVs trigger dsRNA stress and interferon response, increasing CD8+ T cell infiltration and PD-L1 expression, providing mechanistic basis for WEE1 inhibitor + immune checkpoint blockade synergy. WEE1 inhibitor treatment, ERV expression analysis, chromatin immunoprecipitation (H3K9me3/SETDB1), FOXM1 knockdown, dsRNA pathway reporter assays, in vivo tumor models The Journal of experimental medicine Medium 34825915
2011 In Drosophila, wee1 mediates checkpoint-dependent delays in chromosome condensation initiation and rate caused by S-phase and topoisomerase inhibitors; wee1 also mediates delayed anaphase entry in response to chromosome condensation defects independently of the spindle assembly checkpoint. Live imaging of early Drosophila embryos, pharmacological inhibition of S-phase and topoisomerase, genetic analysis with wee1 mutants, spindle assembly checkpoint mutant controls Molecular biology of the cell Medium 22262459
2002 In Xenopus, two Wee1 isoforms (Wee1A and Wee1B) differentially inhibit Cdc2; Wee1B more strongly inhibits Cdc2/oocyte maturation than Wee1A due to its shorter C-terminal regulatory domain, while Wee1B is more labile during meiosis due to N-terminal PEST-like sequences, establishing isoform-specific regulatory domains. Ectopic expression in Xenopus oocytes and embryos, Cdc2 activity assays, domain deletion analysis, developmental cell division assays The EMBO journal Medium 12006499
2019 WEE1 activity is required to protect against nascent DNA degradation during replication stress; WEE1 inhibition combined with PARP inhibitor olaparib produces radiosensitization that is not rescued by nucleosides and requires PARP1 trapping (not just catalytic inhibition), while WEE1 inhibitor alone radiosensitizes via nucleotide depletion/replication stress. Clonogenic survival assays, nucleoside rescue experiments, PARP1 depletion, veliparib vs. olaparib comparison, KRAS-mutant NSCLC cell lines Molecular cancer research Medium 29133592

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 Human Wee1 kinase inhibits cell division by phosphorylating p34cdc2 exclusively on Tyr15. The EMBO journal 433 8428596
2004 M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFbeta-TrCP. Proceedings of the National Academy of Sciences of the United States of America 397 15070733
2016 Targeting WEE1 Kinase in Cancer. Trends in pharmacological sciences 321 27427153
1995 Cell cycle regulation of human WEE1. The EMBO journal 258 7774574
2020 A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target. Journal of hematology & oncology 254 32958072
2013 Wee1 kinase as a target for cancer therapy. Cell cycle (Georgetown, Tex.) 234 24013427
2011 WEE1 kinase targeting combined with DNA-damaging cancer therapy catalyzes mitotic catastrophe. Clinical cancer research : an official journal of the American Association for Cancer Research 209 21562035
1991 Wee1(+)-like gene in human cells. Nature 191 1840647
2019 Sequential Therapy with PARP and WEE1 Inhibitors Minimizes Toxicity while Maintaining Efficacy. Cancer cell 184 31185210
2005 Cyclin-dependent kinase (CDK) phosphorylation destabilizes somatic Wee1 via multiple pathways. Proceedings of the National Academy of Sciences of the United States of America 175 16085715
2017 Regulation of G2/M Transition by Inhibition of WEE1 and PKMYT1 Kinases. Molecules (Basel, Switzerland) 167 29168755
1993 Nim1 kinase promotes mitosis by inactivating Wee1 tyrosine kinase. Nature 143 8515818
1993 Phosphorylation and inactivation of the mitotic inhibitor Wee1 by the nim1/cdr1 kinase. Nature 140 8515817
2003 Wee1-dependent mechanisms required for coordination of cell growth and cell division. Journal of cell science 138 14625382
1992 The wee1 protein kinase is required for radiation-induced mitotic delay. Nature 137 1549179
2007 Cdc25 and Wee1: analogous opposites? Cell division 134 17480229
2000 The G(2) DNA damage checkpoint targets both Wee1 and Cdc25. Journal of cell science 129 10769204
2017 Molecular Pathways: Targeting the Protein Kinase Wee1 in Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 127 28442503
2019 Inhibiting Wee1 and ATR kinases produces tumor-selective synthetic lethality and suppresses metastasis. The Journal of clinical investigation 111 30645202
2017 PARP1 Trapping and DNA Replication Stress Enhance Radiosensitization with Combined WEE1 and PARP Inhibitors. Molecular cancer research : MCR 109 29133592
2022 WEE1 inhibition enhances the antitumor immune response to PD-L1 blockade by the concomitant activation of STING and STAT1 pathways in SCLC. Cell reports 103 35584676
2005 Structure and inhibition of the human cell cycle checkpoint kinase, Wee1A kinase: an atypical tyrosine kinase with a key role in CDK1 regulation. Structure (London, England : 1993) 86 15837193
2020 WEE1 kinase limits CDK activities to safeguard DNA replication and mitotic entry. Mutation research 85 32120135
2021 WEE1 Inhibitor: Clinical Development. Current oncology reports 84 34269904
2016 ATM, ATR, CHK1, CHK2 and WEE1 inhibitors in cancer and cancer stem cells. MedChemComm 84 30108746
2019 Development and Characterization of a Wee1 Kinase Degrader. Cell chemical biology 82 31735695
2021 Clinical Candidates Targeting the ATR-CHK1-WEE1 Axis in Cancer. Cancers 72 33672884
2010 Hsp90 phosphorylation, Wee1 and the cell cycle. Cell cycle (Georgetown, Tex.) 68 20519952
1996 Nuclear tyrosine kinases: from Abl to WEE1. Current opinion in cell biology 68 8791414
2004 Drosophila Wee1 kinase regulates Cdk1 and mitotic entry during embryogenesis. Current biology : CB 67 15589158
1995 Subcellular localisation of human wee1 kinase is regulated during the cell cycle. Journal of cell science 67 7673359
2019 WEE1 kinase inhibitor AZD1775 induces CDK1 kinase-dependent origin firing in unperturbed G1- and S-phase cells. Proceedings of the National Academy of Sciences of the United States of America 66 31712441
2021 Wee1 Kinase: A Potential Target to Overcome Tumor Resistance to Therapy. International journal of molecular sciences 61 34639030
2021 WEE1 inhibition induces anti-tumor immunity by activating ERV and the dsRNA pathway. The Journal of experimental medicine 57 34825915
2018 Strategic development of AZD1775, a Wee1 kinase inhibitor, for cancer therapy. Expert opinion on investigational drugs 57 30102076
2007 Human prostate epithelium lacks Wee1A-mediated DNA damage-induced checkpoint enforcement. Proceedings of the National Academy of Sciences of the United States of America 57 17431037
1997 Myt1: a Wee1-type kinase that phosphorylates Cdc2 on residue Thr14. Progress in cell cycle research 57 9552418
2020 A novel BCMA PBD-ADC with ATM/ATR/WEE1 inhibitors or bortezomib induce synergistic lethality in multiple myeloma. Leukemia 56 32060401
2022 Targeting the DNA Damage Response for Cancer Therapy by Inhibiting the Kinase Wee1. Frontiers in oncology 52 35251998
2022 WEE1 kinase protects the stability of stalled DNA replication forks by limiting CDK2 activity. Cell reports 49 35045293
2013 WEE1 tyrosine kinase, a novel epigenetic modifier. Trends in genetics : TIG 47 23537585
2013 WEE1 inhibition and genomic instability in cancer. Biochimica et biophysica acta 45 23727417
2021 A novel WEE1 pathway for replication stress responses. Nature plants 42 33574575
2021 The ATR-WEE1 kinase module inhibits the MAC complex to regulate replication stress response. Nucleic acids research 40 33450002
2002 The existence of two distinct Wee1 isoforms in Xenopus: implications for the developmental regulation of the cell cycle. The EMBO journal 40 12006499
2020 Wee1 Kinase Inhibitor AZD1775 Effectively Sensitizes Esophageal Cancer to Radiotherapy. Clinical cancer research : an official journal of the American Association for Cancer Research 39 32220892
2019 Anti-Tumor Effects of Wee1 Kinase Inhibitor with Radiotherapy in Human Cervical Cancer. Scientific reports 39 31659268
2018 Targeting WEE1 to enhance conventional therapies for acute lymphoblastic leukemia. Journal of hematology & oncology 39 30068368
2015 Wee1 is required to sustain ATR/Chk1 signaling upon replicative stress. Oncotarget 39 25965828
2018 Activation of WEE1 confers resistance to PI3K inhibition in glioblastoma. Neuro-oncology 37 29016926
2021 A MYBL2 complex for RRM2 transactivation and the synthetic effect of MYBL2 knockdown with WEE1 inhibition against colorectal cancer. Cell death & disease 36 34234118
2013 High expression of wee1 is associated with malignancy in vulvar squamous cell carcinoma patients. BMC cancer 36 23767999
2019 Therapeutic Co-targeting of WEE1 and ATM Downregulates PD-L1 Expression in Pancreatic Cancer. Cancer research and treatment 35 31291716
2017 Wee1 and Cdc25 are controlled by conserved PP2A-dependent mechanisms in fission yeast. Cell cycle (Georgetown, Tex.) 35 28103117
2019 Inhibition of Wee1 sensitizes AML cells to ATR inhibitor VE-822-induced DNA damage and apoptosis. Biochemical pharmacology 33 31014753
2010 Targeting Wee1-like protein kinase to treat cancer. Drug news & perspectives 32 20862394
2024 Discovery of CRBN-Dependent WEE1 Molecular Glue Degraders from a Multicomponent Combinatorial Library. Journal of the American Chemical Society 31 39499896
2017 Synergy of WEE1 and mTOR Inhibition in Mutant KRAS-Driven Lung Cancers. Clinical cancer research : an official journal of the American Association for Cancer Research 31 28821559
2012 Chk1 and Wee1 kinases coordinate DNA replication, chromosome condensation, and anaphase entry. Molecular biology of the cell 31 22262459
2023 SIRT1 deacetylates WEE1 and sensitizes cancer cells to WEE1 inhibition. Nature chemical biology 30 36635566
2018 Cell size-dependent regulation of Wee1 localization by Cdr2 cortical nodes. The Journal of cell biology 30 29514920
2021 WEE1 inhibition reverses trastuzumab resistance in HER2-positive cancers. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 29 33723720
2021 Targeting Wee1 kinase as a therapeutic approach in Hematological Malignancies. DNA repair 29 34390915
2021 Acquired small cell lung cancer resistance to Chk1 inhibitors involves Wee1 up-regulation. Molecular oncology 27 33320980
2020 Structure-activity relationships of Wee1 inhibitors: A review. European journal of medicinal chemistry 27 32688199
2020 FOXM1 drives HPV+ HNSCC sensitivity to WEE1 inhibition. Proceedings of the National Academy of Sciences of the United States of America 27 33093209
2019 Multiple Defects Sensitize p53-Deficient Head and Neck Cancer Cells to the WEE1 Kinase Inhibition. Molecular cancer research : MCR 27 30679201
2023 Adavosertib and beyond: Biomarkers, drug combination and toxicity of WEE1 inhibitors. Critical reviews in oncology/hematology 26 38103761
2022 Cell cycle involvement in cancer therapy; WEE1 kinase, a potential target as therapeutic strategy. Mutation research 25 35247630
2022 The expanding role of WEE1. Cellular signalling 25 35304285
2021 WEE1 inhibition induces glutamine addiction in T-cell acute lymphoblastic leukemia. Haematologica 25 31919076
2014 Pharmacological targeting the ATR-CHK1-WEE1 axis involves balancing cell growth stimulation and apoptosis. Oncotarget 25 25301733
2023 Synthetic and Medicinal Chemistry Approaches Toward WEE1 Kinase Inhibitors and Its Degraders. ACS omega 24 37323408
2022 Selective Wee1 degradation by PROTAC degraders recruiting VHL and CRBN E3 ubiquitin ligases. Bioorganic & medicinal chemistry letters 24 35231578
2019 Synergism Through WEE1 and CHK1 Inhibition in Acute Lymphoblastic Leukemia. Cancers 23 31717700
2016 Wee1 inhibition potentiates Wip1-dependent p53-negative tumor cell death during chemotherapy. Cell death & disease 23 27077811
2021 WEE1 promotes endometriosis via the Wnt/β-catenin signaling pathway. Reproductive biology and endocrinology : RB&E 22 34686198
2014 Casein kinase 1δ-dependent Wee1 protein degradation. The Journal of biological chemistry 22 24817118
2024 An update of predictive biomarkers related to WEE1 inhibition in cancer therapy. Journal of cancer research and clinical oncology 21 38231277
2013 Plant WEE1 kinase is cell cycle regulated and removed at mitosis via the 26S proteasome machinery. Journal of experimental botany 21 23536609
2025 WEE1 inhibition in cancer therapy: Mechanisms, synergies, preclinical insights, and clinical trials. Critical reviews in oncology/hematology 20 40187712
2023 ODF2L acts as a synthetic lethal partner with WEE1 inhibition in epithelial ovarian cancer models. The Journal of clinical investigation 20 36378528
2023 CTPS1 is a novel therapeutic target in multiple myeloma which synergizes with inhibition of CHEK1, ATR or WEE1. Leukemia 20 37898670
2022 HJURP Promotes Malignant Progression and Mediates Sensitivity to Cisplatin and WEE1-inhibitor in Serous Ovarian Cancer. International journal of biological sciences 20 35173547
2021 Recent Advances of WEE1 Inhibitors and Statins in Cancers With p53 Mutations. Frontiers in medicine 20 34671620
2020 PTEN and DNA-PK determine sensitivity and recovery in response to WEE1 inhibition in human breast cancer. eLife 20 32628111
2019 p21 limits S phase DNA damage caused by the Wee1 inhibitor MK1775. Cell cycle (Georgetown, Tex.) 20 30943845
2018 Pharmacophore modeling, multiple docking, and molecular dynamics studies on Wee1 kinase inhibitors. Journal of biomolecular structure & dynamics 19 30052133
2011 Novel insights into maintaining genomic integrity: Wee1 regulating Mus81/Eme1. Cell division 19 22152133
2005 Monitoring the cell cycle by multi-kinase-dependent regulation of Swe1/Wee1 in budding yeast. Cell cycle (Georgetown, Tex.) 19 16123596
2000 Regulation of Wee1 kinase in response to protein synthesis inhibition. FEBS letters 19 11119724
2023 Inhibitors of cell cycle checkpoint target Wee1 kinase - a patent review (2003-2022). Expert opinion on therapeutic patents 18 36620912
2021 Treatment of Melanoma by Nano-conjugate-Delivered Wee1 siRNA. Molecular pharmaceutics 18 34375118
2025 Cyclin E1/CDK2 activation defines a key vulnerability to WEE1 kinase inhibition in gynecological cancers. NPJ precision oncology 17 39755818
2022 WEE1 kinase is a therapeutic vulnerability in CIC-DUX4 undifferentiated sarcoma. JCI insight 17 35315355
2022 Wee1 promotes cell proliferation and imatinib resistance in chronic myeloid leukemia via regulating DNA damage repair dependent on ATM-γH2AX-MDC1. Cell communication and signaling : CCS 17 36575478
2021 MNK1 and MNK2 enforce expression of E2F1, FOXM1, and WEE1 to drive soft tissue sarcoma. Oncogene 17 33564073
2020 Increased HDAC Activity and c-MYC Expression Mediate Acquired Resistance to WEE1 Inhibition in Acute Leukemia. Frontiers in oncology 17 32195191
2020 The Wee1 kinase inhibitor MK1775 suppresses cell growth, attenuates stemness and synergises with bortezomib in multiple myeloma. British journal of haematology 17 32314355
2019 The plant WEE1 kinase is involved in checkpoint control activation in nematode-induced galls. The New phytologist 17 31505035

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