Affinage

MELK

Maternal embryonic leucine zipper kinase · UniProt Q14680

Length
651 aa
Mass
74.6 kDa
Annotated
2026-06-10
100 papers in source corpus 41 papers cited in narrative 41 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

MELK is a Snf1/AMPK-family serine/threonine kinase that couples mitotic cell-cycle progression to the survival and self-renewal programs of proliferating and cancer stem cells (PMID:9136115, PMID:24844244). Its catalytic core comprises the N-terminal kinase domain plus the flanking UBA domain as the minimal active unit, with a C-terminal autoinhibitory region; activity depends on activation-loop autophosphorylation (Thr167/Ser171), reducing conditions, and is inhibited by Ca2+ (PMID:16216881). MELK is activated specifically during M-phase through direct phosphorylation by MPF (CDK1/cyclin B) and MAPK on T-loop and C-terminal residues, explaining its mitotic timing (PMID:16628004), and in the C. elegans ortholog PIG-1 the activation-loop threonine is supplied by the upstream PAR-4/LKB1 kinase to drive asymmetric neuroblast division via cortical nonmuscle myosin II (PMID:23267054, PMID:32946434). Once active, MELK phosphorylates a broad substrate set to sustain proliferation and block apoptosis: it forms a complex with FOXM1 and phosphorylates it (with PLK1) to drive mitotic gene expression (PMID:23404835), phosphorylates and stabilizes EZH2 at Ser220 by blocking K222 ubiquitination in competition with USP36 (PMID:31434700), phosphorylates eIF4B at Ser406 to maintain mitotic synthesis of the anti-apoptotic protein MCL1 (PMID:27528663), and suppresses Bcl-GL-induced apoptosis in a kinase-dependent manner (PMID:17280616). MELK additionally feeds into mTOR signaling through PRAS40 and MLST8 (PMID:31813279, PMID:31915116), engages STAT3 to drive CCL2-dependent immunosuppression (PMID:38970074), and through an FHA-domain interaction with NIPP1 dependent on phospho-Thr478 inhibits an early step of spliceosome assembly independently of its catalytic activity (PMID:14699119). MELK transcription is a direct E2F target and is derepressed when wild-type p53 is lost, via the p53–E2F1–FOXM1 axis (PMID:16144839, PMID:31909186). Despite this extensive substrate literature, CRISPR deletion and acute selective inhibition of MELK across multiple cancer cell types do not impair proliferation under standard conditions, demonstrating a conditional, context-dependent requirement and exposing the poor selectivity of widely used inhibitors such as OTSSP167 (PMID:28926338, PMID:29417930, PMID:30391850).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1997 Medium

    Established MELK's molecular identity, placing an uncharacterized maternal transcript into the Snf1/AMPK kinase family and predicting serine/threonine kinase activity.

    Evidence Differential display cloning and sequence analysis of the kinase domain and leucine zipper in mouse eggs/embryos

    PMID:9136115

    Open questions at the time
    • No functional reconstitution of kinase activity
    • No substrates or pathway identified
  2. 2003 High

    Revealed a kinase-independent function: MELK inhibits spliceosome assembly by docking onto NIPP1, showing that a phosphosite (Thr478) rather than catalysis mediates this activity.

    Evidence FHA-domain binding assays, in vitro spliceosome assembly in nuclear extracts, kinase-dead and T478A mutants

    PMID:14699119

    Open questions at the time
    • Physiological splicing targets in cells not defined
    • Link between mitotic NIPP1-MELK binding and cell-cycle splicing control unresolved
  3. 2005 High

    Defined the enzymatic and regulatory architecture of MELK, including activation-loop autophosphorylation, the minimal active kinase-UBA unit, C-terminal autoinhibition, and redox/Ca2+ control.

    Evidence In vitro kinase assays, autophosphorylation site mapping, domain deletion constructs, Ca2+-binding and mutagenesis

    PMID:16216881

    Open questions at the time
    • Broad substrate specificity leaves physiological substrates undefined
    • Mechanism of Ca2+ inhibition in vivo unclear
  4. 2005 Medium

    Connected MELK to proliferation control by placing its transcription under E2F and pocket-protein regulation and tying it to neural progenitor self-renewal via B-myb.

    Evidence E2F promoter mutagenesis and pocket-protein knockout comparisons; siRNA/overexpression and neurosphere assays in neural progenitors

    PMID:16061694 PMID:16144839

    Open questions at the time
    • Direct MELK substrates driving self-renewal not identified
    • Relationship between transcriptional control and kinase function unresolved
  5. 2006 High

    Explained why MELK acts in mitosis by identifying MPF and MAPK as direct upstream activating kinases that phosphorylate MELK at M-phase-specific sites.

    Evidence M-phase Xenopus egg extract phosphosite mapping by MS plus in vitro kinase assays with recombinant MPF/MAPK

    PMID:16628004

    Open questions at the time
    • Functional consequence of each phosphosite not dissected
    • How activation couples to downstream substrates not addressed
  6. 2006 Medium

    Showed the MELK ortholog PIG-1 controls cell polarity and asymmetric division, not just cell cycle, transforming an apoptotic daughter into a neuron when lost.

    Evidence C. elegans pig-1 loss-of-function with cell-size and fate analysis

    PMID:16774992

    Open questions at the time
    • Molecular substrate driving asymmetry unknown at this stage
    • Upstream activator not yet defined
  7. 2007 High

    Provided the first anti-apoptotic substrate link, showing MELK binds and phosphorylates Bcl-GL and suppresses Bcl-GL-induced death in a kinase-dependent manner.

    Evidence Pull-downs, immunocomplex kinase assay, kinase-dead (D150A) rescue, TUNEL/FACS apoptosis assays

    PMID:17280616

    Open questions at the time
    • Phosphosite on Bcl-GL not mapped
    • In vivo relevance to tumor survival not tested here
  8. 2011 High

    Defined a cytokinetic role: MELK accumulates at the equatorial cortex, associates with anillin, and is required for RhoA-dependent furrowing.

    Evidence Xenopus embryo morpholino knockdown, live imaging, RhoA activation assay, Co-IP with anillin

    PMID:21378312

    Open questions at the time
    • Cytokinetic substrate of MELK not identified
    • Mechanism of cortical recruitment unknown
  9. 2012 High

    Identified PAR-4/LKB1 as the upstream activating kinase of PIG-1/MELK via the conserved activation-loop threonine, defining the kinase cascade controlling asymmetric division.

    Evidence C. elegans genetic epistasis (par-4, strd-1, mop-25.2), T169A activation-loop mutagenesis, centrosome localization imaging

    PMID:23267054

    Open questions at the time
    • Whether LKB1 directly phosphorylates mammalian MELK not shown
    • Centrosomal function of PIG-1 not mechanistically defined
  10. 2013 High

    Established MELK as a driver of cancer stem cell programs by showing it complexes with and phosphorylates FOXM1 (with PLK1) and feeds into c-JUN/p53-dependent survival in glioma stem cells.

    Evidence Co-IP, in vitro kinase assays, shRNA, luciferase reporters, intracranial tumor models

    PMID:23339114 PMID:23404835

    Open questions at the time
    • FOXM1 phosphosite(s) by MELK not fully mapped
    • Distinction between transcriptional autoregulation and direct phosphorylation incomplete
  11. 2013 High

    Linked MELK loss to genome stability, showing depletion causes replication-fork stalling, DNA breaks, and ATM-Chk2-p53-p21 arrest via MDMX loss.

    Evidence siRNA with rescue, gammaH2AX foci, DNA fiber assays, ATM/Chk2/p53/MDMX immunoblotting, cell-cycle flow cytometry

    PMID:23836907

    Open questions at the time
    • Direct MELK substrate at replication forks not identified
    • Later genetic studies question generality of this proliferation requirement
  12. 2013 High

    Provided structural definition of the MELK active site and UBA domain and the basis for nanomolar inhibitor binding.

    Evidence X-ray crystallography of MELK with AMP-PNP and inhibitors

    PMID:23914841

    Open questions at the time
    • No structure of full-length autoinhibited enzyme
    • Conformational basis of activation not captured
  13. 2014 High

    Validated MELK as an oncogenic kinase in basal-like breast cancer while showing it is dispensable for normal development, foreshadowing context-dependence.

    Evidence In vivo kinome ORF tumorigenesis screen, shRNA, KO mouse, caspase and mitosis assays, xenografts; OTSSP167 co-crystal

    PMID:24657156 PMID:24844244

    Open questions at the time
    • RNAi-based dependency later challenged by CRISPR studies
    • OTSSP167 selectivity not yet questioned at this point
  14. 2016 High

    Identified eIF4B-Ser406 as a MELK substrate that sustains mitotic translation of MCL1, providing a direct molecular route from MELK to apoptosis resistance.

    Evidence IP/MS, peptide-library substrate profiling, in vitro kinase assay, protein synthesis and apoptosis assays

    PMID:27528663

    Open questions at the time
    • Other mitotic translation targets not enumerated
    • Contribution relative to other MELK survival pathways unquantified
  15. 2017 High

    Demonstrated MELK stabilizes EZH2 by phosphorylating Ser220 to block K222 ubiquitination, with USP36 identified as the relevant deubiquitinase, linking MELK to epigenetic silencing.

    Evidence Co-IP, quantitative MS for phospho/ubiquitin sites, chemical and genetic MELK inhibition, ubiquitination assays

    PMID:28536141 PMID:31434700

    Open questions at the time
    • Context-specificity (FOXM1-dependent vs independent) across tumor types unresolved
    • Cooperative EZH2-mediated MELK methylation loop incompletely defined
  16. 2017 High

    Defined MELK's redox-coupled regulatory network and TGF-beta/p53 substrate set, showing ZPR9 and Smad2/3/4 activate and stabilize MELK while thioredoxin and Smad7 inhibit it.

    Evidence Co-IP, in vitro kinase assays with phosphosite mutants, CRISPR knockin, adenoviral rescue in obese mice

    PMID:28195154 PMID:29700281

    Open questions at the time
    • Integration of metabolic and mitotic MELK functions unclear
    • In vivo significance of Smad phosphosites in cancer not established
  17. 2017 High

    Broadened MELK function beyond proliferation by showing it phosphorylates HIV-1 capsid Ser149 to trigger uncoating required for viral cDNA synthesis.

    Evidence T-cell genetic screen, siRNA depletion, in vitro capsid kinase assay, phospho-mimetic S149E mutant, uncoating/cDNA assays

    PMID:28683086

    Open questions at the time
    • Relevance to MELK's endogenous cellular role unclear
    • Spatiotemporal control of capsid phosphorylation undefined
  18. 2017 High

    Overturned the prevailing dependency model by showing CRISPR deletion, degradation, and a selective inhibitor (HTH-01-091) leave basal-like breast cancer growth intact, exposing OTSSP167 off-target effects.

    Evidence Five orthogonal perturbations (CRISPR KO, HTH-01-091, chemical degradation, RNAi, CRISPRi)

    PMID:28926338

    Open questions at the time
    • Conditions under which MELK becomes required not yet defined here
    • Reconciliation with prior in vivo screen results incomplete
  19. 2018 High

    Generalized the negative result across cancer types and reframed MELK dependency as conditional, oncogene-like and density/clonogenic-context dependent rather than constitutively essential.

    Evidence Multiple CRISPR KO clones with HTH-01-091, in vitro/in vivo proliferation, clonogenic assays under varying density

    PMID:29417930 PMID:30391850

    Open questions at the time
    • Molecular determinants of the conditional requirement unidentified
    • Predictive biomarkers for MELK dependency absent
  20. 2018 High

    Clarified the mitotic phenotype of acute MELK inhibition as a G2 delay with retarded Aurora/CDK1 activation rather than apoptosis, refining the kinase's cell-cycle role.

    Evidence Selective NVS-MELK8a inhibitor (MIB/MS validated), synchronization, live-cell PCNA microscopy, immunoblotting

    PMID:31896573

    Open questions at the time
    • Direct MELK substrate controlling G2/M timing unknown
    • Reconciliation with non-essentiality across conditions incomplete
  21. 2019 High

    Expanded MELK substrates into mTOR and CDK-inhibitor signaling, showing phosphorylation of PRAS40, MLST8 engagement, and p21-Thr55 phosphorylation controlling cell-cycle and metabolic outputs.

    Evidence Co-IP, in vitro kinase assays with phosphosite mutants, CDK-complex assays, in vivo adenoviral rescue in obese mice, CRISPR knockin

    PMID:31097688 PMID:31813279 PMID:31915116

    Open questions at the time
    • Hierarchy among multiple mTOR-activating mechanisms unresolved
    • Tissue-specific deployment of these substrates unclear
  22. 2020 Medium

    Linked MELK to tumor immune evasion via STAT3-driven CCL2 expression, M2 macrophage polarization, and suppressed CD8+ T-cell recruitment.

    Evidence IP-MS/Co-IP, luciferase assays, RNA-seq, xenograft and metastasis models, macrophage polarization assays

    PMID:38970074

    Open questions at the time
    • STAT3 phosphosite by MELK not mapped
    • Single-lab finding without independent confirmation
  23. 2025 Medium

    Extended MELK function to metabolic and immunogenic-cell-death resistance through PI3K/Akt/mTOR activation, DLAT stabilization, and FABP5 ubiquitination control.

    Evidence Knockdown/overexpression, ubiquitination assays, mitochondrial function assays, Co-IP with FABP5, RFA tumor models

    PMID:37949877 PMID:39871325

    Open questions at the time
    • Direct phosphorylation vs indirect stabilization of these targets unclear
    • Single-lab findings awaiting independent confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved which physiological substrate(s) and genetic/microenvironmental contexts render MELK functionally required, reconciling its rich kinase biology with its dispensability under standard culture.
  • No defined biomarker predicting MELK dependency
  • The conditional requirement seen in clonogenic/stress contexts lacks a mechanistic explanation
  • Whether any single substrate (FOXM1, eIF4B, EZH2) is rate-limiting in vivo is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 9 GO:0016740 transferase activity 4 GO:0060089 molecular transducer activity 3 GO:0140657 ATP-dependent activity 2
Localization
GO:0005634 nucleus 2 GO:0005886 plasma membrane 2 GO:0005815 microtubule organizing center 1 GO:0005856 cytoskeleton 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-8953854 Metabolism of RNA 1
Partners
ANILLINEIF4BEZH2FOXM1MLST8NIPP1PRAS40STAT3

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 MELK encodes a protein with a kinase catalytic domain and a leucine zipper motif, identifying it as a new member of the Snf1/AMPK family of serine/threonine kinases. It was initially identified as a maternal gene expressed in mouse eggs and preimplantation embryos. Differential display analysis of cDNA libraries; sequence analysis of kinase domain and leucine zipper motif Molecular reproduction and development Medium 9136115
2003 MELK interacts with NIPP1 (a spliceosome assembly factor) via the phosphothreonine-binding Forkhead-associated (FHA) domain of NIPP1, dependent on phosphorylation of Thr-478 of MELK. Recombinant MELK potently inhibits an early step of spliceosome assembly in nuclear extracts; a kinase-dead MELK mutant retains this inhibitory effect, but a T478A MELK mutant (which cannot bind NIPP1) does not, demonstrating that MELK inhibits splicing through NIPP1 binding rather than catalytic activity. The NIPP1-MELK interaction is increased in mitotically arrested cells. Protein interaction assay (FHA domain binding), in vitro spliceosome assembly assay in nuclear extracts, kinase-dead and T478A MELK mutants, mitotic cell lysates The Journal of biological chemistry High 14699119
2005 MELK has broad substrate specificity and does not require a specific phosphorylation-site consensus sequence. Autophosphorylation of Thr167 and Ser171 is required for MELK activation. MELK activity requires reducing agents (DTT or glutathione) and is inhibited by physiological Ca2+ concentrations, with MELK identified as a Ca2+-binding protein. The N-terminal catalytic domain plus the flanking ubiquitin-associated (UBA) domain constitutes the minimal catalytically active fragment. A C-terminal fragment functions as an autoinhibitory domain. In vitro kinase assays with recombinant MELK, autophosphorylation site mapping (16 sites identified), domain deletion constructs, Ca2+ binding assays, mutagenesis of Thr167/Ser171 The Journal of biological chemistry High 16216881
2005 MELK (Melk) expression in multipotent neural progenitors (MNPs) is cell cycle regulated. Overexpression of MELK enhances, while knockdown diminishes, neurosphere formation from MNPs, indicating a function in self-renewal. MELK down-regulation down-regulates B-myb expression, which independently mediates MNP proliferation. siRNA knockdown in MNP cultures, transgenic overexpression, neurosphere formation assay, B-myb expression analysis The Journal of cell biology Medium 16061694
2005 MELK transcription is regulated by E2F transcription factors; Melk is a bona fide E2F target gene. Transfection studies and site-directed mutagenesis of E2F binding sites in the Melk promoter confirmed this. 1,25-dihydroxyvitamin D3 represses Melk expression through p107/p130 pocket proteins (but not pRb), consistent with E2F4-mediated repression. Promoter analysis, transfection assays, site-directed mutagenesis of E2F binding sites, p107/p130/pRb knockout cell comparisons The Journal of biological chemistry Medium 16144839
2006 The C. elegans MELK ortholog PIG-1 regulates asymmetric neuroblast divisions: pig-1 mutants produce daughter cells of more equal size and the apoptotic daughter is transformed into its sister fate, generating extra neurons. PIG-1/MELK functions like other PAR-1 family members to regulate cell polarity rather than (only) cell cycle. C. elegans genetic loss-of-function (pig-1 mutants), cell size measurement, cell fate analysis Development (Cambridge, England) Medium 16774992
2006 Xenopus MELK (xMELK) is phosphorylated during M-phase on residues T449, T451, and T481 (specifically detected during mitosis), in addition to T414 and S498. MPF (CDK1/cyclin B) and MAPK pathways are responsible for xMELK phosphorylation in vivo; MPF directly phosphorylates xMELK on T481 in vitro. Phosphorylation by MPF and MAPK enhances MELK kinase activity, explaining mitotic activation of MELK. Phosphorylation site mapping by mass spectrometry in M-phase Xenopus egg extract, in vitro kinase assays with recombinant MPF and MAPK, in vivo phosphorylation analysis Cell cycle (Georgetown, Tex.) High 16628004
2007 MELK physically interacts with Bcl-GL (long isoform of the pro-apoptotic Bcl-2 family member Bcl-G) via its amino-terminal region. MELK phosphorylates Bcl-GL in vitro (immunocomplex kinase assay). Overexpression of wild-type MELK suppresses Bcl-GL-induced apoptosis, while a kinase-dead MELK (D150A) does not, indicating that MELK kinase activity is required for suppression of Bcl-GL-dependent apoptosis. Pull-down assay with recombinant wild-type and kinase-dead MELK, immunocomplex kinase assay, TUNEL and FACS apoptosis analysis, siRNA knockdown Breast cancer research : BCR High 17280616
2011 Xenopus MELK (xMELK) is required for completion of cytokinesis in early embryos. Endogenous xMELK accumulates at the equatorial cortex during anaphase. Overexpression of xMELK impairs cytokinesis and prevents accumulation of activated RhoA at the division furrow. Endogenous xMELK associates and co-localizes with the cytokinesis organizer anillin. Xenopus embryo knockdown (xMELK morpholino), live imaging of xMELK localization, RhoA activation assay at furrow, xMELK overexpression, co-immunoprecipitation with anillin Journal of cell science High 21378312
2012 The C. elegans MELK ortholog PIG-1 acts in the same genetic pathway as PAR-4/LKB1 and its partners STRD-1 and MOP-25.2 to promote asymmetric Q neuroblast division. A conserved threonine in the PIG-1 activation loop (T169), equivalent to the AMPK family phosphorylation site, is essential for PIG-1 activity, consistent with PAR-4 (LKB1) phosphorylating and activating PIG-1. PIG-1 localizes to centrosomes during Q-cell divisions independently of T169 or PAR-4. C. elegans genetic epistasis (double mutants par-4/pig-1, strd-1/pig-1), activation-loop mutagenesis (T169A), centrosome localization by imaging Genetics High 23267054
2013 MELK forms a protein complex with the transcription factor FOXM1 in glioma stem cells (GSCs). MELK phosphorylates and activates FOXM1 in a kinase-dependent manner, leading to upregulation of mitotic regulatory genes. This MELK-dependent FOXM1 activation is further modulated by PLK1, which trans-phosphorylates FOXM1 in the complex. Co-immunoprecipitation (MELK-FOXM1 complex), in vitro kinase assay (FOXM1 phosphorylation), siRNA knockdown, neurosphere formation, luciferase reporter for FOXM1 target genes Stem cells (Dayton, Ohio) High 23404835
2013 MELK is regulated by JNK signaling and forms a complex with the oncoprotein c-JUN specifically in GSCs but not in normal neural progenitors. MELK silencing induces p53 expression, while p53 inhibition induces MELK expression, indicating mutual exclusivity. MELK silencing-mediated GSC apoptosis is partially rescued by both pharmacological p53 inhibition and p53 gene silencing, indicating MELK action is p53-dependent. Co-immunoprecipitation (MELK-c-JUN), shRNA-mediated MELK knockdown, pharmacological p53 inhibition, p53 siRNA, in vivo intracranial tumor model Stem cells (Dayton, Ohio) Medium 23339114
2013 Crystal structures of MELK in complex with AMP-PNP and with nanomolar inhibitors were determined, providing structural characterization of the MELK active site, insight into the role of the UBA domain, and identification of key residues for achieving high binding potency. X-ray crystallography of MELK-AMP-PNP and MELK-inhibitor co-crystal structures Biochemistry High 23914841
2013 Loss of MELK in U87 MG glioblastoma cells causes G1/S cell cycle arrest accompanied by cell death or senescence, mediated by increased p21(WAF1/CIP1) expression. This p21 induction results from consecutive activation of ATM, Chk2, and p53. The p53 activation in MELK-deficient cells is not due to increased p53 stability but to loss of MDMX (an inhibitor of p53 transactivation). MELK loss leads to accumulation of DNA double-strand breaks during replication, stalled replication forks, and reduced fork progression speed. siRNA-mediated MELK knockdown with siRNA-resistant MELK rescue, γH2AX foci analysis, DNA fiber assay (replication fork speed), immunoblotting for ATM/Chk2/p53/MDMX, flow cytometry for cell cycle The Journal of biological chemistry High 23836907
2013 RACK1 (Receptor for Activated protein Kinase C) was identified as a partner of Xenopus MELK (xMELK). RACK1 co-localizes with xMELK at tight junctions in epithelial cells. A truncated RACK1 construct interferes with xMELK localization at cell-cell contacts. Cell-cycle-dependent localization of xMELK differs between epithelial (enriched at apical junctional complex) and mesenchyme-like cells (uniform cortical distribution). Co-immunoprecipitation (xMELK-RACK1), immunofluorescence colocalization, dominant-negative RACK1 construct, live cell imaging Biology open Medium 24167714
2014 Crystal structure of MPK38/MELK (T167E active mutant) in complex with OTSSP167 was determined, showing the detailed protein-inhibitor interactions and confirming that OTSSP167 fits into the MELK active site. X-ray crystallography of MPK38-OTSSP167 co-crystal Biochemical and biophysical research communications High 24657156
2014 MELK is identified as an oncogenic kinase from an in vivo tumorigenesis screen. In basal-like breast cancer (BBC) cells, MELK ablation selectively impairs proliferation (in vitro and in vivo), induces caspase-dependent cell death preceded by defective mitosis. MELK overexpression in BBC is largely dependent on FoxM1 transcriptional regulation. Melk knockout mice are viable and develop normally, indicating MELK is not required for normal development. Kinome-wide ORF in vivo tumorigenesis screen, shRNA knockdown, CRISPR-independent KO mouse, caspase assay, mitosis imaging, xenograft eLife High 24844244
2015 EZH2 is a target of the MELK-FOXM1 complex in GSCs. MELK or FOXM1 promotes GSC radioresistance through regulation of EZH2 expression. The MELK-EZH2 signaling axis is conserved in C. elegans. Gain- and loss-of-function studies (shRNA, overexpression), co-expression analysis in GBM, C. elegans genetic analysis Stem cell reports Medium 25601206
2015 MELK-T1 (a selective MELK inhibitor) triggers rapid, proteasome-dependent degradation of MELK protein. MELK-T1 treatment induces accumulation of stalled replication forks and DNA double-strand breaks, culminating in replicative senescence, ATM activation, CHK2 phosphorylation, p53 phosphorylation, p21 upregulation, and FOXM1 target gene down-regulation in MCF-7 breast cancer cells. Pharmacological inhibition with MELK-T1, proteasome inhibitor rescue, γH2AX foci, immunoblotting for ATM/CHK2/p53/p21/FOXM1 Bioscience reports Medium 26431963
2016 MELK phosphorylates eIF4B at Ser406 during mitosis. MELK and eIF4B form a complex during mitosis (identified by immunoprecipitation/mass spectrometry). The MELK-eIF4B axis regulates protein synthesis during mitosis; specifically, synthesis of the anti-apoptotic protein MCL1 depends on MELK-eIF4B function. Inactivation of MELK or eIF4B reduces MCL1 protein synthesis and induces apoptotic cancer cell death. Immunoprecipitation/mass spectrometry, peptide library substrate profiling, in vitro kinase assay (eIF4B Ser406 phosphorylation), protein synthesis assay, apoptosis assay Proceedings of the National Academy of Sciences of the United States of America High 27528663
2016 MELK kinase inhibition (by MELK-T1, OTS167, and siRNA knockdown) induces p21 protein expression in p53-deficient cancer cells. FOXO1 and FOXO3 are phosphorylated by MELK and are involved in p21 induction after MELK inhibition, indicating a p53-independent mechanism of p21 regulation by MELK. siRNA knockdown of MELK in p53-deficient cell lines, pharmacological inhibition (OTS167), immunoblotting for p21/FOXO1/FOXO3 phosphorylation, flow cytometry cell cycle analysis Oncotarget Medium 28938528
2017 MELK phosphorylates Ser-149 of the HIV-1 capsid protein in the multimerized HIV-1 core, triggering uncoating to promote viral cDNA synthesis. Depletion of MELK inhibits HIV-1 cDNA synthesis with a concomitant delay of capsid disassembly. A phosphorylation-mimetic HIV-1 capsid mutant (S149E) undergoes premature capsid disassembly and earlier cDNA synthesis, but fails to enter the nucleus. Genetic screening of T-cells, MELK depletion (siRNA), in vitro kinase assay (capsid phosphorylation at Ser-149), phospho-mimetic capsid mutant, capsid uncoating assay, HIV-1 cDNA synthesis assay PLoS pathogens High 28683086
2017 MELK promotes melanoma growth by activating the NF-κB pathway via Sequestosome 1 (SQSTM1/p62). MELK is transcriptionally upregulated by the MAPK pathway through transcription factor E2F1 in melanoma cells. SILAC phosphoproteomics after MELK inhibition identified 469 proteins with reduced phosphorylation, 139 of which are known BRAF/MEK substrates, positioning MELK as a downstream mediator of the MAPK pathway. SILAC phosphoproteomics, shRNA knockdown, pharmacological inhibition, NF-κB reporter assay, E2F1 ChIP and promoter analysis Cell reports Medium 29212029
2017 Wild-type p53 suppresses MELK expression by repressing FOXM1 transcription indirectly through reduction of E2F1 binding to the FOXM1 promoter (shown by ChIP assay). Promoter deletion studies identified a FOXM1-binding site in the MELK promoter as the p53-responsive region. Loss of wild-type p53 (by mutation) in TNBC induces MELK expression via derepression of FOXM1. Promoter deletion studies, site-directed mutagenesis, ChIP assay (E2F1 at FOXM1 promoter, FOXM1 at MELK promoter), p53 gain- and loss-of-function, western blotting NPJ breast cancer Medium 31909186
2017 In basal-like breast cancer cells, genetic deletion or acute pharmacological depletion of MELK (using CRISPR/Cas9 KO, selective inhibitor HTH-01-091, chemical-induced protein degradation, shRNA, or CRISPRi) does NOT significantly affect cellular growth under common culture conditions. This contradicts previous RNAi-based findings and reveals that widely-used OTSSP167 has poor selectivity for MELK, and that prior MELK-targeting shRNAs have off-target effects. CRISPR/Cas9 knockout, novel selective MELK inhibitor (HTH-01-091), chemical-induced protein degradation, RNA interference, CRISPR interference eLife High 28926338
2017 MELK bound to EZH2 and phosphorylated EZH2 at S220 in medulloblastoma stem-like cells. This phosphorylation was concomitant with loss of EZH2 K222 ubiquitination, suggesting phosphorylation-dependent protection from ubiquitination. In turn, EZH2 mediates methylation of MELK, creating a cooperative regulatory loop. Co-immunoprecipitation (MELK-EZH2), quantitative mass spectrometry analysis of phosphorylation and ubiquitination sites, loss-of-function studies (shRNA/inhibitors), xenograft models Molecular cancer research : MCR Medium 28536141
2019 MELK phosphorylates EZH2 at S220, preventing K222 ubiquitination and thereby stabilizing EZH2. Quantitative MS confirmed the MELK-dependent increase in EZH2 S220 phosphorylation and concomitant decrease in K222 ubiquitination. MELK inhibition (chemical and genetic) leads to EZH2 ubiquitination and proteasomal degradation. USP36 was identified as the deubiquitinase that removes ubiquitin from EZH2 K222. FOXM1 is not involved in MELK-mediated EZH2 stability in NKTL (unlike in glioma). Quantitative mass spectrometry (phospho- and ubiquitin-site mapping), chemical and genetic MELK inhibition, ubiquitination assay, USP36 identification, tissue microarray Blood High 31434700
2019 MELK phosphorylates PRAS40 (an inhibitory subunit of mTORC1), disrupting the interaction between PRAS40 and raptor, thereby over-activating mTORC1 signaling in clear cell renal cell carcinoma. Loss- and gain-of-function assays (siRNA, overexpression), co-immunoprecipitation (PRAS40-raptor interaction), phosphorylation analysis, mTORC1 pathway readouts Cell transplantation Medium 31813279
2019 MELK interacts with p21 through the CDK-binding region of p21 and the C-terminal domain of MELK. MELK phosphorylates p21 at Thr55, stimulating p21 nuclear translocation, CDK2-p21 and CDK4-p21 complex formation, and inhibition of CDK2-cyclin E and CDK4-cyclin D assembly. p21 phosphorylation by MELK at Thr55 reduces PPARγ transactivation required for adipogenesis. Restoration of p21 by adenoviral delivery in diet-induced obese mice ameliorates metabolic abnormalities in a MELK phosphorylation-dependent manner. Co-immunoprecipitation, in vitro kinase assay (p21 Thr55 phosphorylation), nuclear translocation assay, CDK complex formation assay, adenoviral delivery in mice, CRISPR knockin validation Cell death & disease High 31097688
2018 MELK expression correlates with tumor mitotic activity across cancer types. Multiple MELK-null CRISPR/Cas9 clones across cancer types proliferate at wild-type levels in vitro, under environmental stress, in the presence of cytotoxic chemotherapies, and in vivo. Combination of MELK-KO clones with a highly specific MELK inhibitor (HTH-01-091) shows no specific anti-proliferative phenotype, indicating that acute MELK inhibition is not sufficient for anti-tumor activity as a monotherapy. CRISPR/Cas9 knockout (multiple clones across cancer types), specific MELK inhibitor HTH-01-091, in vitro proliferation assays, xenograft in vivo studies, gene expression correlation analysis eLife High 29417930
2018 SANGUINARINE disrupts the association between STRAP and MELK in colorectal cancer cells by dephosphorylating both proteins, triggering intrinsic (Bax-dependent) apoptosis. The STRAP-MELK interaction is observed in Bax-positive cells but not Bax-negative cells. MELK kinase activity was measured in vitro. Co-immunoprecipitation (STRAP-MELK), immunofluorescence colocalization, in vitro kinase activity assay, flow cytometry apoptosis analysis BMC cancer Medium 29783958
2018 MELK inhibition (NVS-MELK8a, a highly selective MELK inhibitor) delays mitotic entry in triple-negative breast cancer cells, manifesting as lengthened G2 phase (confirmed by live-cell microscopy with fluorescent PCNA). This G2 delay is associated with delayed activation of Aurora A, Aurora B, and CDK1. After this delay, cells enter and complete mitosis, with impaired growth due to cell cycle perturbation rather than apoptosis induction. MIB/MS selectivity profiling, resazurin/crystal violet proliferation assays, double-thymidine synchronization, immunoblotting, live-cell microscopy with fluorescent PCNA The Journal of biological chemistry High 31896573
2017 Smad proteins regulate MPK38/MELK kinase activity in an opposing manner: Smad2/3/4 increase MPK38-mediated ASK1/TGF-β/p53 signaling and stabilize MPK38, while Smad7 decreases MPK38 activity and stability. Smads2/3/4 attenuate the interaction between MPK38 and its negative regulator thioredoxin (Trx), and enhance the interaction with its positive regulator ZPR9. MPK38 phosphorylates Smad2 at S245, Smad3 at S204, Smad4 at S343, and Smad7 at T96; phosphorylation-defective Smad mutants lose the ability to regulate MPK38. Co-immunoprecipitation, in vitro kinase assay (MPK38 phosphorylation of Smads at specific residues), phosphorylation-defective Smad mutants, adenoviral overexpression in HFD-fed obese mice, metabolic phenotyping Cell death & disease Medium 29700281
2017 ZPR9 (zinc finger protein) is an activator of MPK38/MELK. The association of MPK38 and ZPR9 is mediated by specific cysteine residues (Cys269/Cys286 of MPK38, Cys305/Cys308 of ZPR9). MPK38 phosphorylates ZPR9 at Thr252; phosphorylation at Thr252 is required for ZPR9 to enhance MPK38-mediated ASK1, TGF-β, and p53 signaling and stabilize MPK38. ZPR9 competes with the negative regulator thioredoxin (Trx) for MPK38 binding. Co-immunoprecipitation, in vitro kinase assay (ZPR9 Thr252 phosphorylation), cysteine and Thr252 mutants, CRISPR/Cas9 knockin (T252A), conditional knockdown, HFD mouse model Scientific reports High 28195154
2020 MELK interacts with STAT3 (by co-immunoprecipitation) and induces STAT3 phosphorylation, leading to increased expression of its target gene CCL2 in HCC. This CCL2 upregulation promotes M2 macrophage polarization and impairs CD8+ T-cell recruitment, contributing to immunosuppression. MELK is also regulated upstream by miR-505-3p. IP-MS and Co-IP (MELK-STAT3 interaction), luciferase assays, RNA sequencing, murine xenograft and lung metastasis models, macrophage polarization assay Molecular cancer Medium 38970074
2020 In C. elegans, PIG-1/MELK is required for partitioning of CES-1 Snail (anti-apoptotic factor) during asymmetric NSM neuroblast division. PIG-1/MELK acts through phosphorylation and cortical enrichment of nonmuscle myosin II prior to neuroblast division, promoting actomyosin contractility that drives apoptotic fate through CES-1 Snail asymmetric partitioning. pig-1/MELK is controlled by both a ces-1 Snail- and par-4/LKB1-dependent pathway. C. elegans genetics (pig-1 mutants, epistasis with ces-1 and par-4), imaging of nonmuscle myosin II cortical localization, CES-1 Snail partitioning analysis PLoS genetics Medium 32946434
2019 MELK has a direct interaction with MLST8 (a component of both mTORC1 and mTORC2) in endometrial carcinoma cells, demonstrated by co-immunoprecipitation. This interaction activates both mTORC1 and mTORC2 signaling pathways to promote EC progression. MELK expression is transcriptionally regulated by E2F1 (confirmed by ChIP and luciferase assay). Co-immunoprecipitation (MELK-MLST8), chromatin immunoprecipitation (E2F1 at MELK promoter), luciferase reporter assay, knockdown/overexpression studies, xenograft EBioMedicine Medium 31915116
2018 MELK inhibition in DIPG cells functions through reducing inhibitory phosphorylation of PPARγ, resulting in increased nuclear translocation and transcriptional activity of PPARγ (MELK-PPARγ signaling axis identified by RNA sequencing of inhibitor-treated cells). MELK inhibitor (OTSSP167) treatment, RNA sequencing of treated DIPG cells, PPARγ phosphorylation and nuclear translocation analysis, xenograft model Clinical cancer research Medium 30061363
2023 MELK activates the PI3K/mTOR signaling pathway and promotes DLAT (Dihydrolipoamide S-Acetyltransferase) expression, stabilizing mitochondrial function, improving mitochondrial respiration, reducing intracellular ROS, and promoting resistance to elesclomol-induced cuproptosis in HCC. MELK knockdown/overexpression, PI3K/mTOR pathway inhibition, DLAT expression analysis, mitochondrial function assays, elesclomol resistance assay, TOM20 and DLAT oligomer analysis Cell death & disease Medium 37949877
2018 In cancer cells with conditional MELK dependency, abrogation of MELK expression has little effect under high-density common culture conditions but MELK dependency becomes apparent in clonogenic growth assays with both RNAi and CRISPR technologies. This conditional dependency pattern resembles oncogenes (MYC, KRAS) rather than essential genes (classic mitotic kinases). RNAi and CRISPR-mediated MELK depletion under varying cell density conditions, clonogenic assays iScience Medium 30391850
2025 MELK binds to FABP5 (fatty acid-binding protein 5) and affects its ubiquitination through the K48R pathway (K48-linked ubiquitin) to increase FABP5 stability, thereby activating the Akt/mTOR signaling axis and suppressing RFA-mediated immunogenic cell death in HCC. Co-immunoprecipitation (MELK-FABP5), ubiquitination assay (K48R pathway), Akt/mTOR pathway analysis, RFA tumor model, nanoparticle delivery (RGD-LNPs) Military Medical Research Medium 39871325

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 MELK-dependent FOXM1 phosphorylation is essential for proliferation of glioma stem cells. Stem cells (Dayton, Ohio) 172 23404835
2007 Involvement of maternal embryonic leucine zipper kinase (MELK) in mammary carcinogenesis through interaction with Bcl-G, a pro-apoptotic member of the Bcl-2 family. Breast cancer research : BCR 159 17280616
2015 EZH2 protects glioma stem cells from radiation-induced cell death in a MELK/FOXM1-dependent manner. Stem cell reports 147 25601206
2012 The maternal embryonic leucine zipper kinase (MELK) is upregulated in high-grade prostate cancer. Journal of molecular medicine (Berlin, Germany) 134 22945237
2012 Development of an orally-administrative MELK-targeting inhibitor that suppresses the growth of various types of human cancer. Oncotarget 134 23283305
2005 Maternal embryonic leucine zipper kinase (MELK) regulates multipotent neural progenitor proliferation. The Journal of cell biology 131 16061694
1997 New member of the Snf1/AMPK kinase family, Melk, is expressed in the mouse egg and preimplantation embryo. Molecular reproduction and development 109 9136115
2013 Tumor-specific activation of the C-JUN/MELK pathway regulates glioma stem cell growth in a p53-dependent manner. Stem cells (Dayton, Ohio) 100 23339114
2015 MELK-a conserved kinase: functions, signaling, cancer, and controversy. Clinical and translational medicine 99 25852826
2014 MELK is an oncogenic kinase essential for mitotic progression in basal-like breast cancer cells. eLife 98 24844244
2005 Substrate specificity and activity regulation of protein kinase MELK. The Journal of biological chemistry 94 16216881
2023 MELK promotes HCC carcinogenesis through modulating cuproptosis-related gene DLAT-mediated mitochondrial function. Cell death & disease 93 37949877
2016 Maternal Embryonic Leucine Zipper Kinase (MELK) as a Novel Mediator and Biomarker of Radioresistance in Human Breast Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 91 27225691
2017 MELK is not necessary for the proliferation of basal-like breast cancer cells. eLife 87 28926338
2003 Inhibition of spliceosome assembly by the cell cycle-regulated protein kinase MELK and involvement of splicing factor NIPP1. The Journal of biological chemistry 86 14699119
2019 Long noncoding RNA LINC02418 regulates MELK expression by acting as a ceRNA and may serve as a diagnostic marker for colorectal cancer. Cell death & disease 83 31358735
2006 The C. elegans MELK ortholog PIG-1 regulates cell size asymmetry and daughter cell fate in asymmetric neuroblast divisions. Development (Cambridge, England) 82 16774992
2020 MELK is an oncogenic kinase essential for metastasis, mitotic progression, and programmed death in lung carcinoma. Signal transduction and targeted therapy 75 33262323
2016 MELK is an oncogenic kinase essential for early hepatocellular carcinoma recurrence. Cancer letters 74 27693640
2013 Maternal embryonic leucine zipper kinase (MELK): a novel regulator in cell cycle control, embryonic development, and cancer. International journal of molecular sciences 73 24185907
2021 Pharmacological inhibition of MELK restricts ferroptosis and the inflammatory response in colitis and colitis-propelled carcinogenesis. Free radical biology & medicine 70 34144192
2018 MELK expression correlates with tumor mitotic activity but is not required for cancer growth. eLife 66 29417930
2017 MELK Promotes Melanoma Growth by Stimulating the NF-κB Pathway. Cell reports 64 29212029
2020 MELK promotes Endometrial carcinoma progression via activating mTOR signaling pathway. EBioMedicine 60 31915116
2016 Mitotic MELK-eIF4B signaling controls protein synthesis and tumor cell survival. Proceedings of the National Academy of Sciences of the United States of America 60 27528663
2015 MELK-T1, a small-molecule inhibitor of protein kinase MELK, decreases DNA-damage tolerance in proliferating cancer cells. Bioscience reports 60 26431963
2014 Preclinical efficacy of maternal embryonic leucine-zipper kinase (MELK) inhibition in acute myeloid leukemia. Oncotarget 59 25365263
2011 Resistance of colorectal cancer cells to radiation and 5-FU is associated with MELK expression. Biochemical and biophysical research communications 58 21806965
2003 Topological proteomics, toponomics, MELK-technology. Advances in biochemical engineering/biotechnology 57 12934931
2011 Siomycin A targets brain tumor stem cells partially through a MELK-mediated pathway. Neuro-oncology 53 21558073
2017 MELK expression in ovarian cancer correlates with poor outcome and its inhibition by OTSSP167 abrogates proliferation and viability of ovarian cancer cells. Gynecologic oncology 52 28214016
1999 Expression of Melk, a new protein kinase, during early mouse development. Developmental dynamics : an official publication of the American Association of Anatomists 47 10417823
2016 Effective growth-suppressive activity of maternal embryonic leucine-zipper kinase (MELK) inhibitor against small cell lung cancer. Oncotarget 46 26871945
2017 MELK and EZH2 Cooperate to Regulate Medulloblastoma Cancer Stem-like Cell Proliferation and Differentiation. Molecular cancer research : MCR 45 28536141
2017 MELK: a potential novel therapeutic target for TNBC and other aggressive malignancies. Expert opinion on therapeutic targets 45 28764577
2016 Oncogenic roles of TOPK and MELK, and effective growth suppression by small molecular inhibitors in kidney cancer cells. Oncotarget 45 26933922
2011 A functional analysis of MELK in cell division reveals a transition in the mode of cytokinesis during Xenopus development. Journal of cell science 45 21378312
2018 Sanguinarine triggers intrinsic apoptosis to suppress colorectal cancer growth through disassociation between STRAP and MELK. BMC cancer 42 29783958
2021 MELK expression in breast cancer is associated with infiltration of immune cell and pathological compete response (pCR) after neoadjuvant chemotherapy. American journal of cancer research 41 34659896
2017 p53-independent p21 induction by MELK inhibition. Oncotarget 41 28938528
2005 Characterization of the condensin component Cnap1 and protein kinase Melk as novel E2F target genes down-regulated by 1,25-dihydroxyvitamin D3. The Journal of biological chemistry 40 16144839
2021 KLF5-induced BBOX1-AS1 contributes to cell malignant phenotypes in non-small cell lung cancer via sponging miR-27a-5p to up-regulate MELK and activate FAK signaling pathway. Journal of experimental & clinical cancer research : CR 39 33931086
2024 Tumor cell-intrinsic MELK enhanced CCL2-dependent immunosuppression to exacerbate hepatocarcinogenesis and confer resistance of HCC to radiotherapy. Molecular cancer 38 38970074
2014 Multi-kinase inhibitor C1 triggers mitotic catastrophe of glioma stem cells mainly through MELK kinase inhibition. PloS one 38 24739874
2018 MELK Inhibition in Diffuse Intrinsic Pontine Glioma. Clinical cancer research : an official journal of the American Association for Cancer Research 37 30061363
2023 miR-21-5p Inhibits Ferroptosis in Hepatocellular Carcinoma Cells by Regulating the AKT/mTOR Signaling Pathway through MELK. Journal of immunology research 36 37008632
2018 Smad proteins differentially regulate obesity-induced glucose and lipid abnormalities and inflammation via class-specific control of AMPK-related kinase MPK38/MELK activity. Cell death & disease 36 29700281
2006 M-phase MELK activity is regulated by MPF and MAPK. Cell cycle (Georgetown, Tex.) 35 16628004
2016 Preclinical evaluation of biomarkers associated with antitumor activity of MELK inhibitor. Oncotarget 34 26918358
2020 Upregulated MELK Leads to Doxorubicin Chemoresistance and M2 Macrophage Polarization via the miR-34a/JAK2/STAT3 Pathway in Uterine Leiomyosarcoma. Frontiers in oncology 33 32391256
2019 MELK mediates the stability of EZH2 through site-specific phosphorylation in extranodal natural killer/T-cell lymphoma. Blood 33 31434700
2013 Maternal embryonic leucine zipper kinase (MELK) reduces replication stress in glioblastoma cells. The Journal of biological chemistry 32 23836907
2020 Enigmatic MELK: The controversy surrounding its complex role in cancer. The Journal of biological chemistry 31 32350113
2019 Inhibition of MELK produces potential anti-tumour effects in bladder cancer by inducing G1/S cell cycle arrest via the ATM/CHK2/p53 pathway. Journal of cellular and molecular medicine 31 31821699
2020 MEK/MELK inhibition and blood-brain barrier deficiencies in atypical teratoid/rhabdoid tumors. Neuro-oncology 28 31504799
2019 Maternal Embryonic Leucine Zipper Kinase (MELK), a Potential Therapeutic Target for Neuroblastoma. Molecular cancer therapeutics 27 30674566
2017 Genome-wide effects of MELK-inhibitor in triple-negative breast cancer cells indicate context-dependent response with p53 as a key determinant. PloS one 27 28235006
2017 Discovery of a potent inhibitor of MELK that inhibits expression of the anti-apoptotic protein Mcl-1 and TNBC cell growth. Bioorganic & medicinal chemistry 27 28351607
2017 Phosphorylation of the HIV-1 capsid by MELK triggers uncoating to promote viral cDNA synthesis. PLoS pathogens 27 28683086
2021 MELK Inhibition Effectively Suppresses Growth of Glioblastoma and Cancer Stem-Like Cells by Blocking AKT and FOXM1 Pathways. Frontiers in oncology 26 33520717
2013 Structural insight into maternal embryonic leucine zipper kinase (MELK) conformation and inhibition toward structure-based drug design. Biochemistry 26 23914841
2020 Mutant P53 induces MELK expression by release of wild-type P53-dependent suppression of FOXM1. NPJ breast cancer 25 31909186
2020 MELK Accelerates the Progression of Colorectal Cancer via Activating the FAK/Src Pathway. Biochemical genetics 25 32472210
2017 MELK is a novel therapeutic target in high-risk neuroblastoma. Oncotarget 25 29416794
2012 Caenorhabditis elegans PIG-1/MELK acts in a conserved PAR-4/LKB1 polarity pathway to promote asymmetric neuroblast divisions. Genetics 25 23267054
2022 xCT contributes to colorectal cancer tumorigenesis through upregulation of the MELK oncogene and activation of the AKT/mTOR cascade. Cell death & disease 24 35440604
2020 BUB1B Promotes Proliferation of Prostate Cancer via Transcriptional Regulation of MELK. Anti-cancer agents in medicinal chemistry 24 31893996
2021 Discovery of a new molecule inducing melanoma cell death: dual AMPK/MELK targeting for novel melanoma therapies. Cell death & disease 23 33431809
2021 Up-regulation of MELK by E2F1 promotes the proliferation in cervical cancer cells. International journal of biological sciences 23 34671205
2017 Zinc finger protein ZPR9 functions as an activator of AMPK-related serine/threonine kinase MPK38/MELK involved in ASK1/TGF-β/p53 signaling pathways. Scientific reports 23 28195154
2014 The crystal structure of MPK38 in complex with OTSSP167, an orally administrative MELK selective inhibitor. Biochemical and biophysical research communications 23 24657156
2005 Melk-like kinase plays a role in hematopoiesis in the zebra fish. Molecular and cellular biology 23 16024803
2025 MELK prevents radiofrequency ablation-induced immunogenic cell death and antitumor immune response by stabilizing FABP5 in hepatocellular malignancies. Military Medical Research 22 39871325
2022 Circular RNA MELK Promotes Chondrocyte Apoptosis and Inhibits Autophagy in Osteoarthritis by Regulating MYD88/NF-κB Signaling Axis through MicroRNA-497-5p. Contrast media & molecular imaging 22 35992546
2020 Mass spectrometry-based selectivity profiling identifies a highly selective inhibitor of the kinase MELK that delays mitotic entry in cancer cells. The Journal of biological chemistry 22 31896573
2020 MELK/MPK38 in cancer: from mechanistic aspects to therapeutic strategies. Drug discovery today 21 33010478
2018 Corosolic acid induces cell cycle arrest and cell apoptosis in human retinoblastoma Y-79 cells via disruption of MELK-FoxM1 signaling. Oncology reports 21 29620242
2018 MELK as a potential target to control cell proliferation in triple-negative breast cancer MDA-MB-231 cells. Oncology letters 21 29805690
2020 Phillygenin, a MELK Inhibitor, Inhibits Cell Survival and Epithelial-Mesenchymal Transition in Pancreatic Cancer Cells. OncoTargets and therapy 20 32308417
2020 Maslinic Acid Enhances Docetaxel Response in Human Docetaxel-Resistant Triple Negative Breast Carcinoma MDA-MB-231 Cells via Regulating MELK-FoxM1-ABCB1 Signaling Cascade. Frontiers in pharmacology 20 32581798
2019 Thr55 phosphorylation of p21 by MPK38/MELK ameliorates defects in glucose, lipid, and energy metabolism in diet-induced obese mice. Cell death & disease 20 31097688
2019 MELK is Upregulated in Advanced Clear Cell Renal Cell Carcinoma and Promotes Disease Progression by Phosphorylating PRAS40. Cell transplantation 20 31813279
2017 RNA sequencing of esophageal adenocarcinomas identifies novel fusion transcripts, including NPC1-MELK, arising from a complex chromosomal rearrangement. Cancer 19 28640357
2019 MELK inhibition targets cancer stem cells through downregulation of SOX2 expression in head and neck cancer cells. Oncology reports 17 30720113
2016 Identification of IL11RA and MELK amplification in gastric cancer by comprehensive genomic profiling of gastric cancer cell lines. World journal of gastroenterology 17 27920471
2011 Serine/threonine kinase, Melk, regulates proliferation and glial differentiation of retinal progenitor cells. Cancer science 16 21923749
2022 Preclinical assessment of synergistic efficacy of MELK and CDK inhibitors in adrenocortical cancer. Journal of experimental & clinical cancer research : CR 15 36151566
2020 PIG-1 MELK-dependent phosphorylation of nonmuscle myosin II promotes apoptosis through CES-1 Snail partitioning. PLoS genetics 15 32946434
2016 Expression of Maternal Embryonic Leucine Zipper Kinase (MELK) Correlates to Malignant Potentials in Hepatocellular Carcinoma. Anticancer research 14 27798878
2024 DDX56 promotes EMT and cancer stemness via MELK-FOXM1 axis in hepatocellular carcinoma. iScience 13 38827395
2020 High expression of maternal embryonic leucine-zipper kinase (MELK) impacts clinical outcomes in patients with ovarian cancer and its inhibition suppresses ovarian cancer cells growth ex vivo. Journal of gynecologic oncology 13 33078598
2014 Copy number alterations and neoplasia-specific mutations in MELK, PDCD1LG2, TLN1, and PAX5 at 9p in different neoplasias. Genes, chromosomes & cancer 13 24664538
2013 Cell-cycle dependent localization of MELK and its new partner RACK1 in epithelial versus mesenchyme-like cells in Xenopus embryo. Biology open 13 24167714
2024 Upregulation of MELK promotes chemoresistance and induces macrophage M2 polarization via CSF-1/JAK2/STAT3 pathway in gastric cancer. Cancer cell international 12 39135038
2021 PCDHB17P/miR-145-3p/MELK/NF-κB Feedback Loop Promotes Metastasis and Angiogenesis of Breast Cancer. Frontiers in oncology 12 34350110
2017 Caenorhabditis elegans CES-1 Snail Represses pig-1 MELK Expression To Control Asymmetric Cell Division. Genetics 12 28652378
2021 Circ_0007031 Silencing Inhibits Cell Proliferation and Induces Cell Apoptosis via Downregulating MELK at a miR-485-3p-Dependent Way in Colorectal Cancer. Biochemical genetics 11 34322757
2020 Suppression of long non-coding RNA PCAT19 inhibits glioma cell proliferation and invasion, and increases cell apoptosis through regulation of MELK targeted by miR-142-5p. Genes & genomics 11 32980991
2018 A Conditional Dependency on MELK for the Proliferation of Triple-Negative Breast Cancer Cells. iScience 11 30391850
2024 The high expression of TOP2A and MELK induces the occurrence of psoriasis. Aging 10 38382096

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