Affinage

MASTL

Serine/threonine-protein kinase greatwall · UniProt Q96GX5

Length
879 aa
Mass
97.3 kDa
Annotated
2026-06-10
51 papers in source corpus 23 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/10 claims corpus-supported (90%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MASTL (Greatwall kinase) is a serine/threonine kinase that enforces the mitotic and meiotic state by suppressing the principal anti-mitotic phosphatase PP2A/B55, thereby preserving Cdk1-substrate phosphorylation (PMID:19793917, PMID:21156286). Activated during M phase by Cdk1/cyclin B, MASTL drives inactivation of PP2A/B55delta independently of continued MPF activity, and depleting this phosphatase rescues the mitotic-entry failure of Greatwall-depleted extracts (PMID:19793917); in mammalian cells and mice this axis is required for both mitotic entry and exit, with PP2A complexes bearing B55alpha/B55delta acting genetically downstream of MASTL (PMID:21156286, PMID:28224044). MASTL phosphorylates ENSA/ARPP19, which in turn inhibit PP2A/B55 to sustain CDK1 activity and time mitotic re-entry after DNA-damage checkpoint recovery (PMID:26923777). The switch is made bistable by PP1, which associates with MASTL and partially dephosphorylates and deactivates it at mitotic exit, releasing PP2A inhibition (PMID:26872783). MASTL also licenses Cdc20-independent recruitment of cyclin B1 to the APC/C and supports efficient cyclin B1 destruction (PMID:25750436), and in oocytes and primordial germ cells it is required for timely APC/C activation and progression through the meiosis I–II transition (PMID:25246615, PMID:28224044). Its activity is tuned by multiple upstream kinases—AKT (T299), RSK (T297/Thr297), and mTORC1—and by autophosphorylation, with the non-conserved middle region and activation-loop sites governing specificity and activity (PMID:30293837, PMID:31852836, PMID:32123010, PMID:36354735); mTORC1-directed phosphorylation routes MASTL into a metabolic feedback loop that sustains S6K1-dependent phosphorylation of IRS1 and GRB10 to restrain PI3K-AKT signaling (PMID:36354735). MASTL protein levels are set by the E3 ligase E6AP, which is dissociated upon ATM-mediated phosphorylation during DNA damage to stabilize MASTL and enable checkpoint recovery (PMID:37672026), and MASTL transcription is driven by E2F8 (PMID:28605876). Beyond catalysis, MASTL acts kinase-independently by binding MRTF-A to promote its nuclear retention and SRF-dependent transcription of actomyosin contractility genes, driving breast cancer cell motility and invasion (PMID:32311005). In cancer contexts MASTL supports proliferation through PP2A-B55, modulates EGFR stability, and operates a YBX1/PAK4 axis linked to lenvatinib resistance (PMID:29229993, PMID:34331012, PMID:40456026). A recurrent missense mutation (E167D) in MASTL co-segregates with autosomal dominant THC2 thrombocytopenia (PMID:12890928), consistent with a non-mitotic role for MASTL in platelet actin-cytoskeletal dynamics via PP2A-B55 (PMID:30252678).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 2009 High

    Established the core mechanistic logic that Greatwall/MASTL maintains mitosis not by direct substrate phosphorylation alone but by suppressing the anti-mitotic phosphatase PP2A/B55.

    Evidence Xenopus egg extract depletion/add-back with in vitro phosphatase assays and biochemical reconstitution

    PMID:19793917

    Open questions at the time
    • Did not identify the molecular intermediary linking MASTL to PP2A/B55 inhibition
    • Mechanism shown in extract, not yet in intact mammalian cells
  2. 2010 High

    Defined the human MASTL loss-of-function phenotype and localization, establishing it as a Cdk1-downstream effector required across multiple mitotic transitions.

    Evidence RNAi knockdown, immunofluorescence, live-cell imaging and phosphoprotein immunoblotting in human cells

    PMID:20818157

    Open questions at the time
    • Centrosomal relocalization function not mechanistically defined
    • Direct substrates not identified
  3. 2010 High

    Provided in vivo genetic proof that MASTL acts through B55alpha/B55delta-containing PP2A for mitotic exit, anchoring the pathway in mammalian physiology.

    Evidence Conditional knockout mouse models with genetic epistasis and in vivo tumor regression assays

    PMID:21156286

    Open questions at the time
    • Did not resolve the bistability/switch behavior of the system
  4. 2014 High

    Extended MASTL function to meiosis, showing it is needed for timely APC/C activation and the CDK1 rise driving the meiosis I-II transition.

    Evidence Oocyte-specific conditional Mastl knockout mouse, live imaging and immunoblotting

    PMID:25246615

    Open questions at the time
    • Mechanism of APC/C activation timing by MASTL not fully resolved at molecular level
  5. 2015 Medium

    Linked MASTL to APC/C function directly by showing it is required for Cdc20-independent cyclin B1 recruitment and efficient destruction.

    Evidence RNAi with co-immunoprecipitation of cyclin B1 with APC/C in human cells

    PMID:25750436

    Open questions at the time
    • Single-lab Co-IP without reciprocal validation
    • Whether the cyclin B1-APC/C effect is kinase-dependent not resolved
  6. 2016 Medium

    Identified PP1 as the deactivating phosphatase for MASTL, explaining the switch-like, bistable transition of phosphatase activity at mitotic exit.

    Evidence Co-IP of PP1 with MASTL, activity assays and mathematical modeling in human cells

    PMID:26872783

    Open questions at the time
    • Direct PP1-MASTL dephosphorylation sites not fully mapped
    • Single lab
  7. 2016 Medium

    Placed MASTL in DNA-damage checkpoint recovery, showing it times mitotic re-entry through ARPP19/ENSA-mediated PP2A inhibition.

    Evidence RNAi and constitutively active MASTL with cell cycle analysis and CDK1-Tyr15/APC/C immunoblotting

    PMID:26923777

    Open questions at the time
    • Upstream signal coupling DNA damage to MASTL not defined here
    • Single lab
  8. 2017 Medium

    Demonstrated that MASTL's pro-proliferative role in cancer depends on its kinase activity and on PP2A-B55, validating it as a therapeutic target.

    Evidence CRISPR/Cas9 knockout, kinase-dead rescue and in vivo xenograft regression in breast cancer cells

    PMID:29229993

    Open questions at the time
    • Which cancer subsets are dependent not predicted by a marker
    • Single lab
  9. 2017 Medium

    Identified E2F8 as a direct transcriptional activator of MASTL coupling it to cell-cycle gene-expression control and chemoresistance.

    Evidence Dual luciferase promoter assay, ChIP-qPCR and MASTL-inhibition rescue

    PMID:28605876

    Open questions at the time
    • Single lab
    • Broader transcriptional network controlling MASTL not mapped
  10. 2017 High

    Showed MASTL is required for anaphase entry in primordial germ cells, with PP2A genetically downstream, reinforcing the conserved MASTL-PP2A axis in germline mitosis.

    Evidence PGC-specific conditional knockout mouse with Ppp2r1a epistasis and immunofluorescence

    PMID:28224044

    Open questions at the time
    • Cause of female-specific germ cell death downstream not fully defined
  11. 2018 High

    Revealed a non-mitotic role for MASTL in postmitotic platelets, controlling actin-cytoskeletal dynamics through PP2A-B55 and linking it mechanistically to thrombocytopenia.

    Evidence Conditional and knock-in mutant mice, phosphoproteomics and in vivo pharmacological rescue

    PMID:30252678

    Open questions at the time
    • Direct cytoskeletal substrates of the MASTL-PP2A axis in platelets not individually validated
  12. 2018 High

    Identified RSK phosphorylation of MASTL at Thr297 as a mammalian-specific mechanism sustaining MASTL-ENSA activity during prolonged meiotic exit independent of cyclin B.

    Evidence Mouse oocyte live imaging, phosphomutant constructs and kinase inhibition

    PMID:30293837

    Open questions at the time
    • Structural basis of T297-dependent activation not resolved
  13. 2019 High

    Resolved structural and regulatory determinants of MASTL activity, distinguishing autophosphorylation from exogenous activating phosphorylations and assigning specificity to the non-conserved middle region.

    Evidence HDX mass spectrometry, in vitro kinase assays with truncation/point mutants and phosphoproteomics

    PMID:31852836

    Open questions at the time
    • No full-length crystal/cryo-EM structure
    • In-cell relevance of cryptic C-lobe activity not established
  14. 2020 Medium

    Identified AKT phosphorylation at T299 as an activating input linking growth-factor signaling to MASTL-driven mitotic progression.

    Evidence In vitro kinase assay, T299A phosphomutant and loss-of-function in colorectal cancer cells

    PMID:32123010

    Open questions at the time
    • Single lab
    • Interplay of AKT and Cdk1 inputs on MASTL not quantitatively resolved
  15. 2020 High

    Uncovered a kinase-independent function of MASTL, binding MRTF-A to drive its nuclear retention and SRF-dependent contractility gene expression underlying cancer cell invasion.

    Evidence Co-IP, kinase-dead mutant, transcriptome/proteome profiling and invasion assays in breast cancer cells

    PMID:32311005

    Open questions at the time
    • Direct vs indirect nature of MASTL-MRTF-A interaction not crystallographically defined
  16. 2021 Medium

    Connected MASTL to receptor tyrosine kinase signaling in cancer by showing it modulates EGFR protein stability and downstream signaling.

    Evidence Loss/gain-of-function in pancreatic cancer cells and KC/KPC mouse models with EGFR immunoblotting

    PMID:34331012

    Open questions at the time
    • Molecular mechanism of EGFR stabilization not defined
    • Single lab
  17. 2022 High

    Extended the MASTL-PP2A/B55 axis into metabolic signaling, showing mTORC1-phosphorylated MASTL sustains S6K1-dependent IRS1/GRB10 phosphorylation to restrain PI3K-AKT.

    Evidence Genetic depletion, phosphomimetic ENSA/ARPP19 rescue, in vitro mTORC1 kinase assay and in vivo glucose tolerance tests

    PMID:36354735

    Open questions at the time
    • Tissue-specific contribution to systemic metabolism not fully mapped
  18. 2022 Medium

    Refined the activation-site requirements of MASTL, showing the C-tail turn motif S861 is dispensable while activation-loop sites T193/T206 remain required.

    Evidence Inducible conditional Mastl knockout MEFs complemented with phosphosite mutants plus docking

    PMID:36270968

    Open questions at the time
    • Docking-based structural inferences not experimentally validated
    • Single lab
  19. 2022 Low

    Broadened the candidate MASTL substrate repertoire beyond ARPP19/ENSA through an unbiased in vitro screen.

    Evidence SILAC in vitro kinase screen of cell lysates with follow-up kinase assays for candidates

    PMID:35732702

    Open questions at the time
    • Candidate substrates (hnRNPM, YB1, TUBA1C) not validated in cells
    • Single in vitro method per candidate
  20. 2023 High

    Identified the E3 ligase E6AP controlling MASTL turnover and showed ATM-dependent E6AP phosphorylation stabilizes MASTL to enable checkpoint recovery.

    Evidence Co-IP/MS E3 ligase identification, E6AP S218A mutant, ATM inhibition and ubiquitination/recovery assays

    PMID:37672026

    Open questions at the time
    • Ubiquitination site(s) on MASTL not mapped
  21. 2025 Medium

    Defined a MASTL/YBX1/PAK4 effector axis and an STK24 input in hepatocellular carcinoma linking MASTL to drug resistance.

    Evidence Co-IP/MS, ChIP-qPCR and phosphorylation analysis in HCC cells

    PMID:40456026

    Open questions at the time
    • Direct YBX1 phosphosite not validated
    • Single lab
  22. 2025 Medium

    Dissected how loss of Greatwall and PP2A-B55 hyperactivation blocks the meiosis I-II transition by preventing Wee1/Myt1 and APC/C phosphorylation, revealing an APC/C-Erp1 feedback loop.

    Evidence Gwl depletion from Xenopus oocytes with immunoblotting of APC/C substrates and Mos/MAPK components (preprint)

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • Generality to mammalian meiosis not shown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The physiological substrate repertoire of MASTL beyond ARPP19/ENSA, and the structural basis integrating its multiple activating inputs, remain unresolved.
  • No validated in-cell substrates beyond ARPP19/ENSA
  • No full-length structure of MASTL
  • Mechanism of kinase-independent MRTF-A binding undefined

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:0098772 molecular function regulator activity 2 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1640170 Cell Cycle 5 R-HSA-1474165 Reproduction 3 R-HSA-162582 Signal Transduction 3 R-HSA-73894 DNA Repair 2 R-HSA-392499 Metabolism of proteins 1
Partners
APC/CARPP19E6APENSAMRTF-APP1PP2A/B55YBX1

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 Greatwall kinase (Gwl/MASTL) is activated during M phase by Cdk1/cyclin B (MPF), and once activated, promotes inactivation of PP2A/B55delta phosphatase — the major 'antimitotic' phosphatase directed against CDK phosphosites — independently of continued MPF activity. Removal of PP2A/B55delta rescues the inability of Gwl-depleted Xenopus egg extracts to enter M phase. Xenopus egg extract depletion/add-back experiments, in vitro phosphatase activity assays, biochemical reconstitution Molecular biology of the cell High 19793917
2010 Human MASTL (the ortholog of Greatwall) localizes to the nucleus in interphase and re-localizes in part to centrosomes during mitosis when it is active. MASTL RNAi causes G2 delay, slow chromosome condensation, anaphase sister chromatid separation failure, cytokinesis failure, and incomplete cyclin B1 destruction. MASTL supports phosphorylation of mitotic phospho-proteins downstream of cyclin B1-Cdk1, including the APC/C. RNAi knockdown in human cells, immunofluorescence localization, live-cell imaging, immunoblotting of mitotic phosphoproteins Cell cycle (Georgetown, Tex.) High 20818157
2010 In vivo genetic studies in mice demonstrate that Mastl (Greatwall) is required for mitotic exit downstream of Cdk1; Cdc20-null cells can exit mitosis upon inactivation of both Cdk1 and Mastl, and this mitotic exit depends on PP2A phosphatase complexes containing B55α or B55δ regulatory subunits. Genetically engineered mouse models, conditional knockout, in vivo tumor regression assays Cancer cell High 21156286
2014 Mastl is required in mouse oocytes for timely activation of APC/C to allow meiosis I exit and for the rapid rise of Cdk1 activity needed for entry into meiosis II. Mastl-null oocytes reach metaphase I normally but show delayed anaphase I onset and fail to enter meiosis II, reassembling a nuclear structure with decondensed chromatin instead. Oocyte-specific conditional Mastl knockout mouse model, live imaging, immunoblotting The Journal of cell biology High 25246615
2015 MASTL is essential for Cdc20-independent recruitment of cyclin B1 to the mitotic APC/C in prometaphase. This MASTL-directed binding critically supports efficient cyclin B1 destruction after spindle checkpoint release. MASTL RNAi causes anaphase bridges, attributed to insufficient cyclin B1 destruction. RNAi knockdown, co-immunoprecipitation of cyclin B1 with APC/C, cell biology/immunofluorescence Biology open Medium 25750436
2016 PP1 is associated with MASTL and is capable of partially dephosphorylating and deactivating MASTL during mitotic exit. Small decreases in Cdk1 activity during metaphase are sufficient to initiate PP1 reactivation, which in turn partially deactivates MASTL to release inhibition of PP2A, creating a feedback loop that drives complete MASTL deactivation and switch-like phosphatase activation during mitotic exit. Co-immunoprecipitation of PP1 with MASTL, phosphoprotein analysis, mathematical modeling, kinase/phosphatase activity assays in human cells Journal of cell science Medium 26872783
2016 MASTL is critical for timing of mitotic entry after DNA damage checkpoint recovery, acting through ARPP19/ENSA to inhibit PP2A. Constitutively active MASTL promotes CDK1(Tyr15) dephosphorylation and accelerates mitotic re-entry. Downregulation of MASTL or ARPP19/ENSA delays mitotic re-entry after DNA damage and causes premature APC/C activation, causing cells to proceed from G2 directly to G1 skipping mitosis. RNAi knockdown, expression of constitutively active MASTL, cell cycle analysis, immunoblotting for CDK1-Tyr15 and APC/C substrates Scientific reports Medium 26923777
2017 The proliferative function of MASTL in breast cancer cells requires its kinase activity and the presence of PP2A-B55 complexes; genetic ablation of MASTL (CRISPR/Cas9) impairs proliferation of a subset of breast cancer cells and shows therapeutic effect in vivo. CRISPR/Cas9 knockout, RNAi, kinase-dead mutant rescue, in vivo xenograft tumor regression Cell death and differentiation Medium 29229993
2018 In platelets, thrombocytopenia-associated MASTL mutation leads to aberrant platelet activation characterized by hyperstabilized pseudopods and actin polymerization defects mimicking PP2A inhibition. Multiple components of the actin cytoskeleton show abnormal hyperphosphorylation. These defects are rescued in vitro and in vivo by inhibiting upstream kinases PKA, PKC, or AMPK, revealing an unexpected role of Mastl in actin cytoskeletal dynamics in postmitotic cells via PP2A-B55. Conditional megakaryocyte/platelet Mastl knockout mice, knock-in thrombocytopenia-associated mutation mouse model, phosphoproteomics (mass spectrometry), pharmacological rescue in vivo The Journal of clinical investigation High 30252678
2018 RSK (ribosomal S6 kinase) phosphorylates MASTL at Thr297 (conserved only among mammalian MASTLs) after oocyte activation, sustaining CDK1-MASTL-ENSA activity and PP2A suppression despite absence of cyclin B, thereby delaying pronuclear formation. This RSK-MASTL pathway is required for mammalian-specific prolonged meiotic exit and faithful paternal pronucleus formation. Mouse oocyte live imaging, phosphomutant constructs, kinase inhibitor experiments, immunoblotting for MASTL and ENSA phosphorylation Developmental cell High 30293837
2019 The non-conserved middle region (NCMR) of MASTL is crucial for target specificity and activity. Key phosphorylation sites for MASTL activation were determined to arise from autophosphorylation versus exogenous kinases. Hydrogen/deuterium exchange data show the C-lobe forms a stable structure while the N-lobe is dynamic; truncated MASTL constructs retaining a cryptic C-lobe in the NCMR display catalytic activity with different substrate targets. Phosphoproteomic assay with MASTL constructs, hydrogen/deuterium exchange mass spectrometry, in vitro kinase assays with truncation and point mutants Molecular & cellular proteomics : MCP High 31852836
2020 AKT phosphorylates MASTL at residue T299, which plays a critical role in MASTL activation. AKT increases CDK1-mediated phosphorylation and hence the activity of MASTL, which in turn promotes mitotic progression through PP2A inhibition. AKT-mediated proliferation in colorectal cell lines can be attenuated by inhibiting/silencing MASTL. In vitro kinase assay, phospho-site mutant constructs (T299A), immunoblotting, MASTL knockdown/inhibition in colorectal cancer cell lines Molecular and cellular biology Medium 32123010
2020 MASTL promotes cell contractility and breast cancer cell motility/invasion through a kinase-independent mechanism. MASTL associates with MRTF-A (myocardin-related transcription factor A) and increases its nuclear retention and SRF transcriptional activity, regulating genes including GEF-H1, TPM4, VCL, and MYH10. Kinase-dead MASTL is sufficient to regulate cell spreading and MRTF-A/SRF transcriptional activity. Co-immunoprecipitation of MASTL with MRTF-A, kinase-dead MASTL expression, transcriptome and proteome profiling, nuclear fractionation, RNAi knockdown with invasion/migration assays The Journal of cell biology High 32311005
2022 MASTL/Greatwall sustains mTORC1- and S6K1-dependent phosphorylation of IRS1 and GRB10, thereby inhibiting PI3K-AKT activity via the feedback loop downstream of mTORC1. Genetic depletion of MASTL results in inefficient feedback and AKT hyperactivity. These defects are rescued by expression of phosphomimetic ENSA/ARPP19 or inhibition of PP2A/B55 phosphatases. MASTL is directly phosphorylated by mTORC1, limiting PP2A/B55-dependent dephosphorylation of IRS1 and GRB10. Genetic MASTL depletion (mouse and cell line), phosphomimetic ENSA/ARPP19 rescue, in vitro mTORC1 kinase assay on MASTL, phospho-IRS1/GRB10 immunoblotting, in vivo glucose tolerance tests in mice The EMBO journal High 36354735
2022 Phosphorylation of the MASTL C-tail turn motif at S861 (mouse) is dispensable for kinase function in intact mammalian cells, as shown by complementation of tamoxifen-inducible conditional Mastl knockout mouse embryonic fibroblasts with S861A mutant. Activation loop phosphorylations (T193 and T206) remain required. Tamoxifen-inducible conditional Mastl knockout MEFs, genetic complementation with phosphosite mutants, computational molecular docking Journal of biomolecular structure & dynamics Medium 36270968
2022 A SILAC-based whole-cell lysate in vitro kinase screen identified 59 phospho-sites on 67 proteins as potential MASTL substrates beyond ARPP19/ENSA. Subsequent in vitro kinase assays suggested MASTL may phosphorylate hnRNPM, YB1, and TUBA1C under certain in vitro conditions. SILAC in vitro kinase screen with cell lysates, in vitro kinase assays for candidate substrates Scientific reports Low 35732702
2023 E6AP is the E3 ubiquitin ligase that mediates MASTL protein degradation under normal conditions. Upon DNA damage, ATM phosphorylates E6AP at Ser-218, causing E6AP dissociation from MASTL, stabilizing MASTL protein levels, and enabling timely cell cycle recovery from the DNA damage checkpoint. E6AP depletion reduced DNA damage signaling and promoted checkpoint recovery in a MASTL-dependent manner. E3 ligase identification by co-immunoprecipitation and mass spectrometry, E6AP depletion, ATM inhibition, phospho-site mutant of E6AP (S218A), cell cycle recovery assays, ubiquitination assays eLife High 37672026
2017 E2F8 transcription factor directly activates MASTL expression by binding to the MASTL promoter, as validated by western blot, dual luciferase assay, and ChIP-qPCR. E2F8 overexpression shortens cisplatin-induced G2/M arrest by promoting MASTL-mediated mitotic progression, an effect cancelled by MASTL inhibition. Dual luciferase promoter assay, ChIP-qPCR, western blot, MASTL inhibition rescue experiment Biomedicine & pharmacotherapy Medium 28605876
2003 A missense mutation in FLJ14813 (MASTL), E167D (G-to-C at nucleotide 565), segregates perfectly with autosomal dominant thrombocytopenia in a kindred of 51 family members and is absent from 94 unaffected controls, identifying MASTL as a candidate disease gene for THC2 thrombocytopenia. Genetic linkage/segregation analysis, sequencing of family cohort Human heredity Medium 12890928
2009 In vivo morpholino knockdown of MASTL in zebrafish results in deficiency of circulating thrombocytes and decreased expression of thrombopoietin receptor c-mpl and CD41/GpIIb. Both wild-type and E167D mutant MASTL localize to the nucleus when transiently expressed in baby hamster kidney cells. Zebrafish morpholino knockdown, northern blot, transient expression with localization by fluorescence in BHK cells Experimental hematology Medium 19460416
2025 In Xenopus oocytes, loss of Greatwall (Gwl/MASTL) and subsequent hyperactivation of PP2A-B55 prevents phosphorylation of Wee1/Myt1 and the APC/C complex, blocking APC/C activation. This impairs cyclin degradation and partial CDK1 inactivation required at the meiosis I–meiosis II transition, prevents mos-MAPK-Rsk1/2 pathway activation due to insufficient Mos accumulation, and blocks Erp1 degradation, revealing a feedback loop between APC/C and Erp1. Gwl depletion from Xenopus oocytes, immunoblotting for APC/C substrates, cyclin B levels, Wee1/Myt1 phosphorylation, Mos/MAPK pathway components bioRxivpreprint Medium
2025 MASTL facilitates phosphorylation of Y-box binding protein-1 (YBX1); phosphorylated YBX1 transcriptionally activates PAK4, identifying the MASTL/YBX1/PAK4 axis as a downstream effector pathway. STK24, a stress-responsive kinase, can activate MASTL in HCC under lenvatinib exposure. Disruption of this axis by MASTL inhibition restores HCC sensitivity to lenvatinib. Co-immunoprecipitation and mass spectrometry identifying YBX1 as MASTL-associated protein, ChIP-qPCR for YBX1-PAK4 transcriptional regulation, phosphorylation analysis for STK24-MASTL interaction Hepatology (Baltimore, Md.) Medium 40456026
2017 MASTL is required for anaphase entry in proliferating primordial germ cells (PGCs); Mastl-null PGCs enter mitosis normally but fail to proceed beyond a metaphase-like stage, and subsequent cell death eliminates female germ cells. Simultaneous deletion of Ppp2r1a (PP2A α subunit) rescues the mitotic progression defect in Mastl-null PGCs, placing PP2A downstream of Mastl in this pathway. PGC-specific conditional Mastl knockout mouse model, genetic epistasis with Ppp2r1a deletion, immunofluorescence, cell counting Cell discovery High 28224044
2021 MASTL promotes pancreatic cancer progression by modulating EGFR protein stability and kinase signaling; MASTL loss reduces EGFR protein levels and downstream signaling, and combined targeting of MASTL with gemcitabine shows increased cancer cell killing. Loss- and gain-of-function studies in PC cell lines, murine PC models (KC and KPC), immunoblotting for EGFR stability, pharmacological combination experiments Oncogene Medium 34331012

Source papers

Stage 0 corpus · 51 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Targeting mitotic exit leads to tumor regression in vivo: Modulation by Cdk1, Mastl, and the PP2A/B55α,δ phosphatase. Cancer cell 181 21156286
2009 The M phase kinase Greatwall (Gwl) promotes inactivation of PP2A/B55delta, a phosphatase directed against CDK phosphosites. Molecular biology of the cell 160 19793917
2010 MASTL is the human orthologue of Greatwall kinase that facilitates mitotic entry, anaphase and cytokinesis. Cell cycle (Georgetown, Tex.) 120 20818157
2017 Therapeutic relevance of the PP2A-B55 inhibitory kinase MASTL/Greatwall in breast cancer. Cell death and differentiation 76 29229993
2018 MASTL induces Colon Cancer progression and Chemoresistance by promoting Wnt/β-catenin signaling. Molecular cancer 71 30068336
2018 MASTL overexpression promotes chromosome instability and metastasis in breast cancer. Oncogene 52 29743597
2008 Inhibition of DNA binding of the NF-Y transcription factor by the pyrrolobenzodiazepine-polyamide conjugate GWL-78. Molecular cancer therapeutics 49 18483319
2003 FLJ14813 missense mutation: a candidate for autosomal dominant thrombocytopenia on human chromosome 10. Human heredity 49 12890928
2014 Mastl kinase, a promising therapeutic target, promotes cancer recurrence. Oncotarget 45 25373736
2016 PP1 initiates the dephosphorylation of MASTL, triggering mitotic exit and bistability in human cells. Journal of cell science 43 26872783
2015 Boolean modeling identifies Greatwall/MASTL as an important regulator in the AURKA network of neuroblastoma. Cancer letters 39 26616283
2015 Genome-wide siRNA Screen Identifies the Radiosensitizing Effect of Downregulation of MASTL and FOXM1 in NSCLC. Molecular cancer therapeutics 35 25808837
2018 MASTL inhibition promotes mitotic catastrophe through PP2A activation to inhibit cancer growth and radioresistance in breast cancer cells. BMC cancer 34 29976159
2016 MASTL(Greatwall) regulates DNA damage responses by coordinating mitotic entry after checkpoint recovery and APC/C activation. Scientific reports 34 26923777
2018 The Oncogenic Functions of MASTL Kinase. Frontiers in cell and developmental biology 33 30555827
2014 Mastl is required for timely activation of APC/C in meiosis I and Cdk1 reactivation in meiosis II. The Journal of cell biology 31 25246615
2020 MASTL: A novel therapeutic target for Cancer Malignancy. Cancer medicine 26 32692487
2017 E2F8 confers cisplatin resistance to ER+ breast cancer cells via transcriptionally activating MASTL. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 26 28605876
2009 In vivo inactivation of MASTL kinase results in thrombocytopenia. Experimental hematology 26 19460416
2022 The MASTL/PP2A cell cycle kinase-phosphatase module restrains PI3K-Akt activity in an mTORC1-dependent manner. The EMBO journal 23 36354735
2018 Thrombocytopenia-associated mutations in Ser/Thr kinase MASTL deregulate actin cytoskeletal dynamics in platelets. The Journal of clinical investigation 23 30252678
2021 MASTL regulates EGFR signaling to impact pancreatic cancer progression. Oncogene 22 34331012
2020 MASTL promotes cell contractility and motility through kinase-independent signaling. The Journal of cell biology 21 32311005
2017 Mastl overexpression is associated with epithelial to mesenchymal transition and predicts a poor clinical outcome in gastric cancer. Oncology letters 17 29344164
2020 MKI-1, a Novel Small-Molecule Inhibitor of MASTL, Exerts Antitumor and Radiosensitizer Activities Through PP2A Activation in Breast Cancer. Frontiers in oncology 16 33117702
2018 Mitosis perturbation by MASTL depletion impairs the viability of thyroid tumor cells. Cancer letters 16 30445205
2020 AKT Regulates Mitotic Progression of Mammalian Cells by Phosphorylating MASTL, Leading to Protein Phosphatase 2A Inactivation. Molecular and cellular biology 14 32123010
2022 Therapeutic natural compounds Enzastaurin and Palbociclib inhibit MASTL kinase activity preventing breast cancer cell proliferation. Medical oncology (Northwood, London, England) 12 35599277
2019 Inflammatory cytokine-induced expression of MASTL is involved in hepatocarcinogenesis by regulating cell cycle progression. Oncology letters 11 30867746
2022 The MASTL-ENSA-PP2A/B55 axis modulates cisplatin resistance in oral squamous cell carcinoma. Frontiers in cell and developmental biology 10 36247015
2021 Discovery and Characterization of a Novel MASTL Inhibitor MKI-2 Targeting MASTL-PP2A in Breast Cancer Cells and Oocytes. Pharmaceuticals (Basel, Switzerland) 10 34358073
2015 MASTL promotes cyclin B1 destruction by enforcing Cdc20-independent binding of cyclin B1 to the APC/C. Biology open 10 25750436
2019 Molecular Basis of the Mechanisms Controlling MASTL. Molecular & cellular proteomics : MCP 9 31852836
2018 RSK-MASTL Pathway Delays Meiotic Exit in Mouse Zygotes to Ensure Paternal Chromosome Stability. Developmental cell 8 30293837
2022 MASTL is enriched in cancerous and pluripotent stem cells and influences OCT1/OCT4 levels. iScience 6 35677646
2022 SILAC kinase screen identifies potential MASTL substrates. Scientific reports 6 35732702
2020 Kinase-Independent Functions of MASTL in Cancer: A New Perspective on MASTL Targeting. Cells 6 32640605
2017 MASTL is essential for anaphase entry of proliferating primordial germ cells and establishment of female germ cells in mice. Cell discovery 6 28224044
2023 The ATM-E6AP-MASTL axis mediates DNA damage checkpoint recovery. eLife 5 37672026
2025 First-in-class dual inhibitors of MASTL and Aurora A kinase: Discovery of selective cyclohexa[b]thiophenes with potent anticancer activity. European journal of medicinal chemistry 4 40367676
2024 Activity-based protein profiling and global proteome analysis reveal MASTL as a potential therapeutic target in gastric cancer. Cell communication and signaling : CCS 4 39138495
2024 Discovery of Highly Selective Inhibitors of Microtubule-Associated Serine/Threonine Kinase-like (MASTL). Journal of medicinal chemistry 4 39499084
2023 Targeted inhibition of MASTL kinase activity induces apoptosis in breast cancer. Life sciences 4 37931742
2025 The MASTL/YBX1/PAK4 axis regulated by stress-activated STK24 triggers lenvatinib resistance and tumor progression in HCC. Hepatology (Baltimore, Md.) 3 40456026
2024 IL-22 regulates MASTL expression in intestinal epithelial cells. American journal of physiology. Gastrointestinal and liver physiology 3 38771154
2022 Genetic complementation screening and molecular docking give new insight on phosphorylation-dependent Mastl kinase activation. Journal of biomolecular structure & dynamics 2 36270968
2025 MASTL Promotes Hepatocellular Carcinoma Progression and Paclitaxel Resistance Through Mitotic Catastrophe. Cancer science 1 41347427
2026 Therapeutic potential of targeting MASTL in lung adenocarcinoma. Scientific reports 0 41629603
2026 Development of MKI-3: A Potent and Selective MASTL Inhibitor with Improved Efficacy for Cancer Treatment. Journal of medicinal chemistry 0 41857504
2024 Deficiency of mastl, a mitotic regulator, results in cell detachment from developing tissues of zebrafish embryos. Frontiers in cell and developmental biology 0 38533088
2023 The ATM-E6AP-MASTL axis mediates DNA damage checkpoint recovery. bioRxiv : the preprint server for biology 0 36865136

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