Affinage

MCM4

DNA replication licensing factor MCM4 · UniProt P33991

Length
863 aa
Mass
96.6 kDa
Annotated
2026-06-10
86 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MCM4 is a core subunit of the replicative MCM helicase that drives origin licensing and DNA unwinding during eukaryotic genome replication (PMID:9305914, PMID:10567526). Within the catalytic MCM4/6/7 sub-complex, MCM4 contributes single-stranded DNA binding and inter-subunit contacts while ATP binding by MCM6 and the conserved ATPase motifs of MCM7 are critical for helicase activity; an MCM4 zinc-finger mutation that impairs DNA binding elevates helicase activity and promotes trimer dissociation, implicating the zinc finger in trimer-trimer assembly, and N-terminal deletions abolish activity despite intact hexamer formation (PMID:10567526, PMID:12207017, PMID:30184107). The complex assembles into ring-shaped toroidal hexamers that unwind DNA 3'-to-5' by a steric-exclusion 'pump-in-ring' mechanism, binding only the leading-strand template, and is preferentially activated by thymine-rich single-stranded and bubble/Y-fork substrates that mimic activated origins (PMID:9305914, PMID:13679365, PMID:10884341, PMID:14609960, PMID:20860810). MCM4 activity is gated by phosphorylation of its N-terminal serine/threonine-rich domain (NSD): CDK1/CDK2 phosphorylation at multiple defined N-terminal Ser/Thr sites inactivates the MCM4/6/7 helicase and reduces chromatin affinity, enforcing once-per-cycle licensing and contributing to ATR-CHK1-CDK2 checkpoint-mediated fork inhibition, while Cdc7/DDK phosphorylation of the NSD relieves an intrinsic inhibitory activity to license S-phase progression and promote Cdc45 chromatin loading (PMID:8901561, PMID:10748114, PMID:11454864, PMID:12714602, PMID:17046832, PMID:20054399, PMID:24740181). MCM4 chromatin loading depends on ORC and Cdc6/Cdc18 and marks unreplicated chromatin, from which it is displaced as forks pass; a conserved MCM4 motif is required for MCM2-7 double-hexamer formation and extensive origin unwinding, and a cryo-EM ORC-Cdc6-Cdt1-MCM2-7 loading intermediate identifies MCM4 as the key ATPase whose hydrolysis reorganizes the complex, closes the ring, and releases Cdt1 (PMID:31385807, PMID:8838654, PMID:10747035, PMID:39747125). Hypomorphic and destabilizing MCM4 mutations (Chaos3/F345I, D573H, cancer-derived G364R/G486D) reduce MCM complex stability or helicase activity and produce chromosomal instability and tumorigenesis, and a human MCM4 splice-site/truncating deficiency causes genomic instability, NK-cell (CD56dim) deficiency, and adrenal insufficiency (PMID:17143284, PMID:23133403, PMID:25661590, PMID:27794528, PMID:22354167, PMID:22354170).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1995 Medium

    Defining the physical context of MCM4 established that it is not a solo protein but a stable subunit of a multiprotein MCM assembly, framing all later mechanistic work as the biology of a complex.

    Evidence Co-immunoprecipitation, gel filtration and nuclear fractionation of human MCM4/hCdc21

    PMID:7601140

    Open questions at the time
    • Did not resolve full hexamer stoichiometry or which subunit carries catalytic activity
    • Phosphorylation-localization link was correlative
  2. 1996 High

    Linking MCM4 chromatin behavior to the cell cycle answered whether MCM4 acts at replication origins, showing it marks unreplicated chromatin and is displaced by passing forks.

    Evidence Confocal microscopy, subcellular fractionation and BrdU co-localization in HeLa cells; Xenopus cell-free extract chromatin-binding assays

    PMID:8605878 PMID:8838654

    Open questions at the time
    • Did not establish the biochemical activity of MCM4 on DNA
    • Mechanism of fork-coupled displacement unresolved
  3. 1996 High

    Identifying cdc2/cyclinB phosphorylation of MCM4 that lowers chromatin affinity answered how the licensing system is shut off after S phase to prevent re-replication.

    Evidence In vitro cdc2/cyclinB kinase assay plus in vivo chromatin-binding analysis in Xenopus

    PMID:8901561

    Open questions at the time
    • Specific phosphoacceptor sites not yet mapped
    • Did not show direct effect on helicase catalysis
  4. 1997 High

    Demonstrating that an immunopurified MCM4/6/7 complex carries intrinsic ATPase and 3'-5' helicase activity answered whether MCMs are the replicative helicase machinery.

    Evidence Biochemical purification from HeLa, anti-MCM4 immunodepletion, helicase and ATPase assays

    PMID:9305914

    Open questions at the time
    • Did not assign catalytic roles to individual subunits
    • Activity measured outside the full MCM2-7 context
  5. 1999 High

    Dissecting subunit roles by ATPase-motif mutagenesis answered which subunit drives catalysis versus substrate binding, assigning ATP binding to MCM6 and ssDNA binding to MCM4.

    Evidence Recombinant insect-cell reconstitution with ATPase motif mutagenesis and separable activity assays

    PMID:10567526

    Open questions at the time
    • MCM7 contribution not yet defined
    • Coupling of ssDNA binding to unwinding not mechanistically resolved
  6. 1999 High

    Showing cyclin-driven nuclear exclusion of Mcm4 in budding yeast established a second layer of licensing control acting on MCM localization independent of catalytic inhibition.

    Evidence Live-cell imaging of GFP-Mcm4 with cyclin mutant genetics

    PMID:10559985

    Open questions at the time
    • Relative importance of nuclear exclusion vs direct phosphoinhibition unclear
    • Transport machinery not identified
  7. 2000 High

    Mapping CDK phosphorylation of the Mcm4 N-terminus to direct in vitro helicase inactivation answered how cell-cycle kinases mechanistically silence the helicase, beyond just chromatin affinity.

    Evidence Cyclin A/Cdk2 in vitro kinase assay coupled to helicase assays of phosphorylated MCM4/6/7

    PMID:10748114

    Open questions at the time
    • Individual phosphosites not yet defined
    • Did not address ssDNA-binding vs catalytic step affected
  8. 2000 High

    Structural visualization and inhibitory-subunit assays answered how the catalytic core is organized and how non-core MCMs modulate it, showing toroidal hexamers inhibited by Mcm2 and Mcm3/5.

    Evidence Negative-stain EM, gel-shift and helicase inhibition assays with Mcm2 and Mcm3/5

    PMID:10884341

    Open questions at the time
    • Inhibition mechanism within full MCM2-7 not resolved
    • No high-resolution structure
  9. 2000 High

    Defining the genetic requirements for chromatin loading answered how MCM4 is recruited to origins, establishing dependence on ORC and Cdc6/Cdc18 and replication-coupled release.

    Evidence Fission yeast in situ chromatin-binding assays with orc1/cdc18 mutants and re-replication assays; Xenopus phosphoisoform/chromatin-binding analysis

    PMID:10747035 PMID:10779356

    Open questions at the time
    • Order of loading relative to other MCM subunits not resolved
    • Phosphoisoform identities defined only operationally
  10. 2002 High

    Systematic domain mutagenesis answered which structural elements of each subunit are essential, defining MCM7 ATPase motifs as catalytically essential and the MCM4 zinc finger and N-terminus as required for assembly and activity.

    Evidence ATPase, zinc-finger and N-terminal deletion mutagenesis with in vitro ATPase/helicase assays

    PMID:12207017

    Open questions at the time
    • Did not place these elements in a high-resolution structure
    • Inter-subunit ATP-site geometry not resolved
  11. 2003 High

    Defining the unwinding mechanism with strand-specific and branched substrates answered how the helicase translocates, establishing a 3'-5' steric-exclusion 'pump-in-ring' mode activated by thymine-rich origin-like DNA.

    Evidence In vitro helicase assays with nicked DNA, Holliday junctions, bubbles and Y-forks plus base-substitution controls

    PMID:13679365 PMID:14609960

    Open questions at the time
    • Mechanism studied on the MCM4/6/7 core not the full MCM2-7
    • Physiological origin substrate recognition only inferred
  12. 2003 High

    Placing MCM4 phosphorylation within the replication-block checkpoint answered how DNA damage signaling restrains the helicase, showing ATR-CHK1 and CDK2 act sequentially to inactivate MCM4/6/7.

    Evidence Phospho-specific antibodies, kinase-inhibitor epistasis and in vitro helicase assays of CDK2-phosphorylated MCM4/6/7 in HeLa cells; correlated with reduced DNA synthesis

    PMID:12714602 PMID:15037254

    Open questions at the time
    • Direct in vivo demonstration that helicase inhibition stops forks not fully resolved
    • Phosphorylation-DNA synthesis link partly correlative
  13. 2006 High

    Mapping individual N-terminal phosphosites and their kinases answered the molecular logic of MCM4 phosphoregulation, distinguishing CDK1 G2/M sites from CDK2 interphase sites and identifying nucleolar Ser32-phospho MCM4.

    Evidence Site-specific phospho-antibodies with CDK1/CDK2 mutants, chromatin fractionation and immunofluorescence; site-directed mutagenesis relieving CDK2 inhibition

    PMID:11454864 PMID:16519687

    Open questions at the time
    • Functional role of nucleolar phospho-MCM4 unclear
    • Interplay between the multiple sites not fully resolved
  14. 2006 High

    Identifying Cdc7/DDK phosphorylation of the MCM4 N-terminus that promotes Cdc45 loading answered how origins are positively activated, complementing the inhibitory CDK arm.

    Evidence Phospho-amino-acid antibodies, Cdc7 siRNA and Cdc7-deficient ES cells, Cdc45 chromatin assays and MCM4 N-terminal deletion rescue

    PMID:17046832

    Open questions at the time
    • Redundancy among MCM2/4/6 phospho-targets not fully separated
    • Direct DDK substrate sites only partially mapped
  15. 2006 High

    Showing that a viral kinase hijacks MCM4 phosphosites to inactivate the helicase answered whether the licensing switch can be subverted to arrest the host cell cycle.

    Evidence In vitro EBV-PK kinase assay, helicase assays, phosphosite mutagenesis and EBV-PK expression causing HeLa growth arrest

    PMID:17005684

    Open questions at the time
    • Full set of EBV-PK target sites on MCM4/MCM6 not defined
    • In vivo relevance during EBV infection not established here
  16. 2008 Medium

    Genetic dissection of the NSD answered how CDK and DDK signals are integrated on Mcm4, showing CDK phosphorylation counteracts excess DDK activity to balance origin firing.

    Evidence mcm4-5A alanine mutant with DDK gain-of-function epistasis in S. cerevisiae; Mcm4 CTD truncation analysis in fission yeast

    PMID:18321994 PMID:18753627

    Open questions at the time
    • Single-lab genetic epistasis for the CDK-counteracting model
    • Molecular mechanism of CTD-mediated helicase suspension at stalled forks not biochemically reconstituted
  17. 2010 High

    Defining DDK's essential function as relief of an intrinsic NSD inhibitory activity answered why DDK is required for replication, pinpointing the Mcm4 NSD as the key regulatory element.

    Evidence Genetic epistasis in S. cerevisiae with mcm4 NSD deletion and CDK-bypass mutations plus checkpoint assays; gel filtration/arginine-finger analysis establishing the hexamer as minimal functional unit

    PMID:20054399 PMID:20860810

    Open questions at the time
    • Structural basis of NSD-intrinsic inhibition unresolved
    • Hexamer quaternary findings from single lab in vitro
  18. 2012 High

    Characterizing destabilizing and dominant-negative MCM4 mutations answered how MCM4 dysfunction causes disease, linking reduced complex stability/activity to chromosomal instability and tumorigenesis.

    Evidence Mouse genetics (Chaos3/F345I, D573H/Sdl), yeast minichromosome and inactive-helicase assays, fibroblast breakage and tumor genomic analysis

    PMID:17143284 PMID:23133403

    Open questions at the time
    • Tissue specificity of tumor phenotypes not mechanistically explained
    • Quantitative threshold of MCM activity for instability unclear
  19. 2012 High

    Identifying a human hypomorphic MCM4 deficiency answered the in-vivo physiological consequences, linking MCM4-dependent cell division to NK-cell maturation, genomic stability, and adrenal steroidogenic cell maintenance.

    Evidence Patient fibroblast genomic instability with WT rescue, NK proliferation/maturation assays, isoform Western blots and Mcm4-depleted mouse adrenal histology

    PMID:22354167 PMID:22354170

    Open questions at the time
    • Why NK CD56dim and adrenal lineages are selectively vulnerable not fully explained
    • Role of the preserved 85-kDa isoform unclear
  20. 2015 Medium

    Biochemical characterization of cancer- and Chaos3-derived MCM4 mutations answered which molecular defects drive instability, distinguishing assembly defects (F345I, G486D) from selective helicase loss (G364R).

    Evidence Co-purification, native gel, co-IP, helicase/ATPase/ssDNA and stability assays for F345I, G364R and G486D; localization in HeLa cells

    PMID:22668557 PMID:25661590 PMID:27794528

    Open questions at the time
    • Single-lab biochemical characterizations
    • Direct in vivo causal link from each mutation to specific cancers not established
  21. 2014 High

    Sub-dividing the NSD into proximal and distal segments answered how a single domain controls two distinct outcomes, separating checkpoint repression of late origins from CDK-regulated fork progression.

    Evidence Whole-genome replication profiling and single-molecule DNA fiber analysis of mcm4 NSD mutants under stress; concerted NSD/Sld3/Dbf4 epistasis

    PMID:24740181 PMID:26733669

    Open questions at the time
    • Molecular partners reading each NSD segment not all identified
    • Mechanism mostly defined in yeast
  22. 2018 Medium

    Defining the requirement of the extreme MCM4 N-terminus and phosphomimetic destabilization answered how CDK phosphorylation mechanistically disables licensing, by reducing hexamer stability while preserving the N-terminal residues needed for activity.

    Evidence N-terminal deletion/point mutations (Arg10/Arg11), helicase and S-phase assays, and phosphomimetic complex-stability assays in HeLa cells

    PMID:30184107

    Open questions at the time
    • Single-lab phosphomimetic model
    • Direct demonstration in the full MCM2-7 ring lacking
  23. 2019 High

    Single-molecule analysis of an MCM4 conserved motif answered the assembly step it controls, showing it is required for stable MCM2-7 double-hexamer formation and extensive unwinding but not for initial loading or Cdc45/GINS recruitment.

    Evidence Single-molecule fluorescence kinetics of WT and mutant Mcm2-7 loading with unwinding and activator-recruitment readouts

    PMID:31385807

    Open questions at the time
    • Structural detail of the double-hexamer interface contributed by MCM4 not resolved here
    • Link to in-vivo origin function inferred
  24. 2025 High

    A cryo-EM loading intermediate answered the catalytic role of MCM4 ATP hydrolysis in pre-RC formation, identifying MCM4 as the key ATPase whose hydrolysis closes the ring and releases Cdt1.

    Evidence Cryo-EM of ORC-Cdc6-Cdt1-MCM2-7 with Mcm2/Mcm5 interface and ATPase-deficient Mcm4 mutants, helicase loading and Cdt1 release assays

    PMID:39747125

    Open questions at the time
    • Full activation transition to a translocating helicase not captured
    • Coordination of MCM4 hydrolysis with other subunit ATP sites not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the regulatory NSD phosphorylation network and the MCM4 ATPase activity are structurally integrated within the assembled, activated CMG helicase at a moving fork remains unresolved.
  • No structure of phosphorylated MCM4 in an active CMG
  • Mechanism by which NSD inhibition is relieved during firing not structurally defined
  • Tissue-specific disease vulnerability not mechanistically explained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 5 GO:0003677 DNA binding 4 GO:0140097 catalytic activity, acting on DNA 4 GO:0016787 hydrolase activity 3
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3 GO:0005730 nucleolus 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-69306 DNA Replication 3
Partners
CDC45CDC7MCM2MCM3MCM5MCM6MCM7RB1
Complex memberships
MCM2-7 hexamerMCM4/6/7 helicase coreORC-Cdc6-Cdt1-MCM2-7 loading intermediate (pre-RC)

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 A DNA helicase activity is intrinsically associated with an MCM4/6/7 protein complex purified from HeLa cells. The complex (600 kDa, equal amounts of MCM4, MCM6, MCM7) has both ATPase and DNA helicase activities; immunodepletion with anti-MCM4 antibody abolished helicase activity. The helicase translocates 3' to 5' along single-stranded DNA and requires hydrolyzable ATP or dATP. Biochemical purification, immunodepletion with anti-MCM4 antibody, DNA helicase displacement assay, ATPase assay The Journal of biological chemistry High 9305914
1999 The DNA helicase activity of the Mcm4/6/7 complex is intrinsic to the complex and does not require other factors. Mutagenesis of conserved ATPase motifs showed that ATP binding by Mcm6 is critical for helicase activity, while Mcm4 plays a role in single-stranded DNA binding. The two activities (helicase and ssDNA binding) can be separated biochemically. Recombinant protein expression in insect cells, ATPase motif mutagenesis, DNA helicase assay, ssDNA binding assay Molecular and cellular biology High 10567526
1996 Xenopus MCM4 is phosphorylated by cdc2/cyclinB kinase in a cell-cycle-dependent manner (starting at S phase, peaking in mitosis), and this phosphorylation dramatically reduces MCM4's affinity for chromatin, providing a mechanism to inactivate the MCM complex from late S phase through mitosis and prevent re-replication. In vitro kinase assay (cdc2/cyclinB), in vivo phosphorylation analysis in Xenopus embryos and cell-free extracts, chromatin binding assay Proceedings of the National Academy of Sciences of the United States of America High 8901561
1999 In budding yeast, both G1-phase (Cln) and B-type cyclins (CDKs) cause nuclear exclusion of Mcm4, thereby preventing assembly of prereplicative complexes. Only B-type cyclins trigger origin firing, but G1 cyclins can reduce the nuclear Mcm4 pool before S phase entry. Live-cell imaging of GFP-tagged Mcm4 in budding yeast, genetic analysis with cyclin mutants Nature cell biology High 10559985
2000 Cyclin A/Cdk2 phosphorylates the amino-terminal region of Mcm4 in the Mcm4/6/7 complex and this phosphorylation inactivates the complex's DNA helicase activity in vitro. In vitro kinase assay with cyclin A/Cdk2, DNA helicase assay of phosphorylated MCM4/6/7 complex The Journal of biological chemistry High 10748114
2001 Six specific Ser/Thr residues in the N-terminal region of Mcm4 are required for Cdk2/cyclin A phosphorylation. Alanine substitution at these six sites largely relieves CDK2-mediated inhibition of Mcm4/6/7 helicase activity. Anti-phosphothreonine antibodies showed that one site is phosphorylated mainly in mitotic phase HeLa cells, and Mcm4/6/7 isolated from mitotic cells has reduced helicase activity. Site-directed mutagenesis of Mcm4 phosphorylation sites, in vitro kinase assay, DNA helicase assay, phase-specific anti-phosphoantibody Western blot The Journal of biological chemistry High 11454864
2003 Mcm4/6/7 is a ring-shaped heterohexamer that unwinds DNA by a 'pump in ring' mechanism involving steric exclusion: it binds only one strand (the leading strand template) during unwinding, stops at nicks in either strand, and actively translocates along duplex DNA to drive branch migration of Holliday junctions. Unwinding polarity is 3' to 5'. Biochemical helicase assays with strand-specific substrates including nicked DNA and Holliday junctions, mechanistic analysis The Journal of biological chemistry High 13679365
2000 Electron microscopy shows Mcm4/6/7 complex forms toroidal ring structures with a central channel (~600 kDa). ssDNA binding affinity is comparable to SV40 T antigen. Mcm2 inhibits the helicase by disrupting nucleoprotein complex formation, and Mcm3/5 complex also inhibits Mcm4/6/7 helicase activity. Electron microscopy (negative staining), gel-shift assays, helicase inhibition assays with Mcm2 and Mcm3/5 Journal of molecular biology High 10884341
2002 Conserved ATPase motifs of Mcm7 are essential for both ATPase and helicase activities of the Mcm4/6/7 complex; Mcm7 alone has no activity but contributes through inter-subunit interaction. A zinc finger mutant of Mcm4 with impaired DNA binding showed elevated helicase activity and tended to dissociate into trimers, implicating the Mcm4 zinc finger in trimer-trimer interactions. Deletion of the Mcm4 N-terminal 35 or 112 residues abolished helicase activity despite intact hexamer formation. ATPase motif mutagenesis, zinc finger mutagenesis, N-terminal deletion analysis, ATPase and helicase assays in vitro The Journal of biological chemistry High 12207017
2003 Human MCM4 is a target of the replication block checkpoint. ATR-CHK1 and CDK2 kinases act consecutively to phosphorylate MCM4 in cells treated with hydroxyurea or exposed to UV. CDK2-mediated phosphorylation of MCM4 inactivates the MCM4/6/7 helicase activity in vitro, suggesting checkpoint-mediated helicase inhibition blocks fork progression. Phospho-specific antibody analysis in HeLa cells, kinase inhibitor studies, in vitro helicase assay with CDK2-phosphorylated MCM4/6/7 The Journal of biological chemistry High 12714602
2006 Cdc7 kinase phosphorylates MCM4 at specific N-terminal (S/T)(S/T)P residues during S phase on chromatin. This phosphorylation promotes association of Cdc45 with chromatin. Deletion of the N-terminal 150 amino acids of MCM4 impairs growth; adding back segments with Cdc7 target sequences partially rescues growth. Combined N-terminal mutations in MCM2, MCM4 and MCM6 are lethal, suggesting redundant but essential roles for Cdc7-mediated phosphorylation of these subunits. Phospho-amino acid-specific antibody analysis, siRNA knockdown of Cdc7, Cdc7-deficient ES cells, chromatin binding assay for Cdc45, MCM4 N-terminal deletion mutants, growth rescue assays The Journal of biological chemistry High 17046832
2006 EBV protein kinase (EBV-PK) phosphorylates MCM4 (at Thr-19 and Thr-110, CDK2/CDK1 target sites) in vitro and in cells, leading to inactivation of MCM4/6/7 helicase activity. Expression of EBV-PK in HeLa cells caused cell growth arrest. Mutating the six N-terminal Ser/Thr CDK sites reduces CDK2/cyclin A inhibition but not EBV-PK inhibition, indicating EBV-PK also phosphorylates additional sites (MCM6 and other MCM4 sites). In vitro kinase assay with EBV-PK, helicase activity assay, phosphosite mutagenesis, EBV-PK expression in HeLa cells Journal of virology High 17005684
2006 Site-specific phosphorylation of human MCM4 at seven N-terminal sites (Ser3, Thr7, Thr19, Ser32, Ser54, Ser88, Thr110) was characterized during the cell cycle. Sites Thr7, Thr19, Ser32, Ser54, Ser88, and Thr110 are enhanced in G2/M phase requiring CDK1; Ser3 and Ser32 require CDK2 during interphase. MCM4 phosphorylated at Ser32 was enriched in the nucleolus throughout the cell cycle. Anti-phospho-MCM4 site-specific antibodies, temperature-sensitive CDK1 mutant, dominant-negative CDK2 mutant, chromatin fractionation, immunofluorescence The FEBS journal High 16519687
2010 In S. cerevisiae, the N-terminal serine/threonine-rich domain (NSD) of Mcm4 contains both inhibitory and facilitating activities for DNA replication. DDK's sole essential function is to relieve the inhibitory activity within the NSD. An mcm4 mutant lacking the inhibitory NSD combined with CDK-bypass mutations allows DNA synthesis in G1 when CDKs and DDK are limited. Without DDK, CDK phosphorylation at the distal NSD becomes critical. DDK-null cells fail to activate the intra-S checkpoint in hydroxyurea. Genetic epistasis in S. cerevisiae using mcm4 NSD deletion and CDK-bypass mutations, cell cycle analysis, checkpoint activation assays Nature High 20054399
2003 Mcm4/6/7 helicase activity is specifically activated by thymine-rich single-stranded DNA. The helicase is activated by synthetic bubble structures mimicking activated replication origins and by Y-fork structures with thymine-rich 3'-tails. Substituting thymine clusters with guanine in a human lamin B2 origin abolished activation. In vitro helicase assay with defined oligonucleotide substrates (bubbles, Y-forks, ssDNA), sequence substitution mutants The EMBO journal High 14609960
2008 Truncation of the Mcm4 C-terminal domain (CTD) in fission yeast (mcm4-c84) causes hypersensitivity to dNTP depletion and delays recovery from replication block. The Mcm4 CTD is required to suspend MCM helicase activity at stalled forks: mcm4-c84 cells show increased RPA association at stalled forks (excess ssDNA) without affecting GINS or MCM association, indicating uncoupled helicase activity at stalled forks. Fission yeast genetics, chromatin immunoprecipitation (RPA, MCM, GINS at stalled forks), 2D gel electrophoresis of replication intermediates, replication checkpoint activation assay Proceedings of the National Academy of Sciences of the United States of America High 18753627
2014 The N-terminal serine/threonine-rich domain (NSD) of Mcm4 contains two functionally distinct segments: the proximal segment (adjacent to DDK-docking domain) mediates checkpoint repression of late-origin firing, and the distal segment (N-terminus) regulates replication fork progression and checkpoint signaling via CDK phosphorylation. Under replication stress, mutations in these segments alter temporal origin activation and fork progression independently. Whole-genome replication profile analysis, single-molecule DNA fiber analysis, mcm4 NSD mutants in S. cerevisiae under replication stress Proceedings of the National Academy of Sciences of the United States of America High 24740181
2019 A conserved motif in Mcm4 is required for MCM2-7 double-hexamer formation but not for initial loading of two individual hexamers or initial DNA melting. Mutations in this motif allow hexamer-hexamer contact but form unstable double hexamers. Double-hexamer formation is required for extensive origin DNA unwinding but not for recruitment of Cdc45 or GINS helicase-activation proteins. Single-molecule fluorescence microscopy, kinetic analysis of WT and mutant Mcm2-7 loading, DNA unwinding assays, helicase-activation protein recruitment assays eLife High 31385807
1996 Human MCM4/hCdc21 is entirely nuclear in interphase HeLa cells and exists in two populations: nucleosolic and chromatin-bound. The chromatin-bound population colocalizes with unreplicated (not replicating) chromatin and is displaced as replication forks pass through, indicating MCM4 marks unreplicated chromatin and is displaced upon replication. High-resolution confocal microscopy, subcellular fractionation, co-localization with BrdU replication foci Journal of cell science High 8838654
1996 Xenopus cdc21 (MCM4 ortholog) binds to decondensing chromatin at the end of mitosis in an underphosphorylated state, remains bound during initiation of DNA replication, and is displaced as replication forks progress. Partial phosphorylation precedes displacement; hyperphosphorylation of the entire pool occurs at mitosis, likely by cdc2/cyclin B kinase. Xenopus cell-free extracts, chromatin binding assay, phosphorylation analysis, immunofluorescence, detergent extraction The EMBO journal High 8605878
2000 In fission yeast, mcm4/cdc21 chromatin association occurs during anaphase B (earlier than in budding yeast). Chromatin binding of mcm4 requires orc1 and cdc18 (Cdc6 homolog). Release from chromatin occurs during S phase and requires active DNA replication. Overexpression of cdc18 causes mcm4-dependent re-replication. GFP-tagging, in situ chromatin binding assay with detergent permeabilization, genetic analysis (orc1, cdc18 mutants), re-replication assay The EMBO journal High 10747035
2000 Distinct phosphoisoforms of Xenopus Mcm4 regulate MCM complex function: an intermediately phosphorylated Mcm4 is present in a transient interphase complex that associates with chromatin/pre-RCs; complete dephosphorylation of Mcm4 prevents chromatin binding; hyperphosphorylation (mitotic, by Cdc2-cyclin B and other kinases) also prevents chromatin binding. Chromatin-associated phosphorylation of Mcm4 and Mcm2 during pre-RC activation requires nuclear transport and is independent of Cdk2-cyclin E. Xenopus cell-free extracts, phosphatase treatment, kinase inhibitors, chromatin binding assays, cell cycle stage-specific protein analysis Molecular and cellular biology High 10779356
2005 Mcm4/6/7 on a bubble substrate makes symmetric dual contacts with 5'-proximal 25 nt ssDNA segments adjacent to branch points, suggesting double-hexamer formation. Loss of thymine residues from one strand significantly decreases bidirectional unwinding efficiency. The helicase is inhibited by increasing GC content of the duplex; cytosine-guanine to cytosine-inosine substitution restores unwinding. In vitro helicase assay with defined bubble, fork, and extension substrates, sequence-substitution mutants Nucleic acids research High 15917436
2008 In S. cerevisiae, S-CDK and DDK cooperate through phosphorylation of Mcm4's N-terminal domain. Five CDK phosphoacceptor sites in Mcm4's N-terminal domain (mcm4-5A) are required for normal origin firing efficiency at low temperatures. Loss of these CDK sites causes synthetic lethality with DDK gain-of-function conditions (mcm5-bob1 or DDK overexpression), suggesting CDK phosphorylation of Mcm4 counteracts excess DDK activity. mcm4-5A alanine substitution mutant, genetic epistasis with DDK gain-of-function alleles, S-phase cyclin deletion analysis Molecular biology of the cell Medium 18321994
2016 In S. cerevisiae, concerted activities of Mcm4 NSD, Sld3, and Dbf4 control late origin firing and fork progression: late origins fire under genotoxic stress only when controls on all three are simultaneously eliminated. The Mcm4 NSD proximal segment and Sld3 function in parallel for fork progression under replication stress; hypomorphic sld3 mutations are suppressed by mcm4 NSD mutations. Whole-genome replication profile analysis in yeast, genetic epistasis with mcm4 NSD, sld3, and dbf4 mutations under genotoxic stress Genome research High 26733669
2012 The Mcm4(Chaos3) mutation (F345I in mouse, corresponding to F391I in yeast) destabilizes the MCM complex and reduces chromatin-bound MCM levels, causing chromosomal instability and impaired DNA replication. The equivalent yeast mutation causes minichromosome loss. Homozygous Mcm4 disruption causes preimplantation lethality; Mcm4(Chaos3) is hypomorphic. Mouse genetics, yeast minichromosome maintenance assay, embryonic fibroblast chromosomal breakage assay, mouse cancer phenotyping Nature genetics High 17143284
2012 The Mcm4(D573H) mutation in mice produces a biologically inactive helicase (shown in S. cerevisiae) that incorporates into MCM complexes and renders them inactive in a dominant-negative manner. Sdl heterozygous mice develop T-ALL with genomic instability (micronucleation, amplifications, deletions including Notch1), without loss-of-heterozygosity at Mcm4. Exome sequencing, mouse genetics (heterozygous and homozygous analysis), S. cerevisiae functional assay, micronucleus assay, genomic analysis of tumors PLoS genetics High 23133403
2015 The Chaos3 mutation (F345I) in MCM4 reduces MCM6 interaction and impairs MCM4/6/7 hexameric complex formation. Nuclear localization and MCM complex assembly are affected by this mutation in human cells, and the defect in MCM6 interaction may reduce chromatin binding of the MCM2-7 complex. Co-expression and co-purification in insect cells, co-immunoprecipitation in human cells, native gel analysis of complex formation Journal of biochemistry Medium 22668557
2015 A G364R mutation of MCM4 detected in human skin cancer cells reduces DNA helicase activity of the MCM4/6/7 complex to 30-50% of wild-type, without affecting complex formation with MCM6/7, ssDNA binding, or ATPase activity. The mutant MCM4 is correctly localized to nuclease-sensitive chromatin in HeLa cells. In vitro reconstitution of MCM4/6/7, helicase assay, ATPase assay, ssDNA binding assay, co-purification, nuclear fractionation Journal of biochemistry Medium 25661590
2010 In S. cerevisiae, Mcm4/6/7 forms a hexameric (not trimeric) functional unit. ATP and ATPγS shift the equilibrium from smaller oligomers toward hexamers. Arginine finger mutants that disrupt inter-subunit ATP sites abolish full activity, and Mcm4/6/7 binds DNA as a hexamer, demonstrating the hexamer is the minimal functional unit. Oligomeric analysis by gel filtration, arginine finger mutagenesis, ATPase assay, helicase assay, DNA binding assay BMC biochemistry Medium 20860810
2017 A G486D mutation of MCM4 found in endometrial cancer cells (within the conserved MCM-box) destabilizes the MCM4/6/7 complex and promotes degradation of the mutant MCM4 protein. The mutation likely affects interaction with MCM7. Expression of mutant MCM4 in HeLa cells causes abnormal nuclear morphology, indicating perturbed DNA replication. Co-expression and co-purification, stability assay, nuclear morphology analysis in HeLa cells Journal of biochemistry Medium 27794528
2018 The N-terminal 35 amino acids of human MCM4, including Arg10 and Arg11, are required for DNA helicase activity of MCM4/6/7. Phosphomimetic substitutions at six CDK sites (Glu at positions 3, 7, 19, 32, 54, 110) reduce hexameric MCM4/6/7 complex stability, suggesting CDK phosphorylation destabilizes the complex as part of the licensing control mechanism. N-terminal deletion and point mutations of MCM4, helicase assay, S-phase progression analysis in HeLa cells, phosphomimetic mutagenesis and complex stability assay Journal of biochemistry Medium 30184107
2025 Cryo-EM structure of an ORC-Cdc6-Cdt1-MCM2-7 intermediate reveals a remodeled, fully-closed Mcm2/Mcm5 interface. The Mcm5 C-terminus (C5) contacts Orc3 and recognizes the closed ring state. Normal helicase loading triggers Mcm4 ATP hydrolysis, which reorganizes the MCM2-7 complex and releases Cdt1. Defective MCM2-7 ring closure (via Mcm2/Mcm5 interface mutations) leads to MCM2-7 ring splitting and complex disassembly. Mcm4 is identified as the key ATPase regulating pre-RC formation. Cryo-EM structural determination, Mcm2/Mcm5 interface mutations, ATPase-deficient Mcm4 mutants, helicase loading assay, Cdt1 release assay Nature communications High 39747125
1995 Human MCM4/hCdc21 forms a stable trimeric complex with two novel human Mcm proteins (p85Mcm and p105Mcm). BM28/Mcm2 is more loosely associated with this trimeric complex. The highly phosphorylated mitotic form of hCdc21 is less tightly bound to nuclear structures than the underphosphorylated form. Co-immunoprecipitation, gel filtration, nuclear fractionation European journal of biochemistry Medium 7601140
2012 Partial MCM4 deficiency in humans (due to splice-site mutation causing hypomorphic truncation) results in genomic instability in fibroblasts, rescued by WT MCM4 expression. The NK CD56(dim) subset deficiency is due to impaired proliferation/maturation of NK CD56(bright) cells, which is tightly dependent on MCM4-dependent cell division. Patient fibroblast genomic instability assay, MCM4 WT rescue, NK cell proliferation and maturation assay The Journal of clinical investigation High 22354167
2012 MCM4 mutation in humans (c.71-1insG) causes absence of the major 96-kDa isoform while preserving the 85-kDa isoform. Mcm4-depleted mice show abnormal adrenal morphology with non-steroidogenic GATA4+/Gli1+ cells replacing steroidogenic zona fasciculata cells, reducing steroidogenic cell number. Western blot of patient samples (isoform characterization), histological analysis of Mcm4-depleted mouse adrenal glands The Journal of clinical investigation Medium 22354170
2004 There is an inverse correlation between levels of MCM4 phosphorylation and DNA synthesis during replication checkpoint control and after checkpoint release in HeLa cells. Higher MCM4 phosphorylation (at CDK sites) correlates with lower DNA synthesis, consistent with phosphorylation-mediated inhibition of MCM4/6/7 helicase during checkpoint. Anti-phospho-MCM4 antibodies, BrdU incorporation assay, hydroxyurea and UV treatment of HeLa cells Journal of structural biology Medium 15037254
2011 The antibiotic heliquinomycin inhibits MCM4/6/7 helicase by binding to ssDNA and interfering with the ssDNA binding activity of the MCM4/6/7 complex. At IC50 of 2.5 µM, it inhibits cellular DNA replication without activating the replication checkpoint, suggesting it primarily targets the replicative helicase. In vitro helicase assay, gel-retardation assay for heliquinomycin-ssDNA interaction, cellular DNA replication inhibition assay Journal of biochemistry Medium 22023799
2004 Underphosphorylated pRb interacts with MCM4 (identified by two-hybrid assay using LexA-Rb(561-660)), and a pRb-MCM4-CTF/NF-I complex was detected in Nalm-6 cells. MCM4's C-terminus contains a conserved motif with homology to the DNA-binding domain of CTF/NF-I. Yeast two-hybrid assay, immunoprecipitation of pRb-MCM4-CTF/NF-I complex from cells, sequence analysis Biochemical and biophysical research communications Low 15081408

Source papers

Stage 0 corpus · 86 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 A DNA helicase activity is associated with an MCM4, -6, and -7 protein complex. The Journal of biological chemistry 461 9305914
2006 A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice. Nature genetics 259 17143284
2010 The Dbf4-Cdc7 kinase promotes S phase by alleviating an inhibitory activity in Mcm4. Nature 248 20054399
2012 Partial MCM4 deficiency in patients with growth retardation, adrenal insufficiency, and natural killer cell deficiency. The Journal of clinical investigation 227 22354167
2012 MCM4 mutation causes adrenal failure, short stature, and natural killer cell deficiency in humans. The Journal of clinical investigation 192 22354170
1999 Biochemical analysis of the intrinsic Mcm4-Mcm6-mcm7 DNA helicase activity. Molecular and cellular biology 180 10567526
1999 G1-phase and B-type cyclins exclude the DNA-replication factor Mcm4 from the nucleus. Nature cell biology 172 10559985
2006 Phosphorylation of MCM4 by Cdc7 kinase facilitates its interaction with Cdc45 on the chromatin. The Journal of biological chemistry 154 17046832
1996 Human replication proteins hCdc21, hCdc46 and P1Mcm3 bind chromatin uniformly before S-phase and are displaced locally during DNA replication. Journal of cell science 137 8838654
2003 Mcm4,6,7 uses a "pump in ring" mechanism to unwind DNA by steric exclusion and actively translocate along a duplex. The Journal of biological chemistry 136 13679365
1992 Fission yeast cdc21+ belongs to a family of proteins involved in an early step of chromosome replication. Nucleic acids research 117 1454522
1996 Phosphorylation of MCM4 by cdc2 protein kinase inhibits the activity of the minichromosome maintenance complex. Proceedings of the National Academy of Sciences of the United States of America 116 8901561
1996 Chromatin binding, nuclear localization and phosphorylation of Xenopus cdc21 are cell-cycle dependent and associated with the control of initiation of DNA replication. The EMBO journal 102 8605878
2014 Juvenile hormone-receptor complex acts on mcm4 and mcm7 to promote polyploidy and vitellogenesis in the migratory locust. PLoS genetics 95 25340846
2000 Chromatin binding of the fission yeast replication factor mcm4 occurs during anaphase and requires ORC and cdc18. The EMBO journal 90 10747035
2003 Identification of MCM4 as a target of the DNA replication block checkpoint system. The Journal of biological chemistry 87 12714602
1995 A human homologue of the yeast replication protein Cdc21. Interactions with other Mcm proteins. European journal of biochemistry 86 7601140
1987 The CDC8 transcript is cell cycle regulated in yeast and is expressed coordinately with CDC9 and CDC21 at a point preceding histone transcription. Experimental cell research 84 3305044
1996 Fission yeast cdc21, a member of the MCM protein family, is required for onset of S phase and is located in the nucleus throughout the cell cycle. The EMBO journal 83 8631307
2015 Proteome-wide analysis of mutant p53 targets in breast cancer identifies new levels of gain-of-function that influence PARP, PCNA, and MCM4. Proceedings of the National Academy of Sciences of the United States of America 80 25733866
2000 Inhibition of Mcm4,6,7 helicase activity by phosphorylation with cyclin A/Cdk2. The Journal of biological chemistry 80 10748114
2000 Electron microscopic observation and single-stranded DNA binding activity of the Mcm4,6,7 complex. Journal of molecular biology 78 10884341
2001 Phosphorylation of Mcm4 at specific sites by cyclin-dependent kinase leads to loss of Mcm4,6,7 helicase activity. The Journal of biological chemistry 76 11454864
1995 Molecular cloning of cDNA encoding mouse Cdc21 and CDC46 homologs and characterization of the products: physical interaction between P1(MCM3) and CDC46 proteins. Nucleic acids research 72 7610039
2016 MCM4 and MCM7, potential novel proliferation markers, significantly correlated with Ki-67, Bmi1, and cyclin E expression in esophageal adenocarcinoma, squamous cell carcinoma, and precancerous lesions. Human pathology 64 27476776
2002 Roles of Mcm7 and Mcm4 subunits in the DNA helicase activity of the mouse Mcm4/6/7 complex. The Journal of biological chemistry 64 12207017
1976 Yeast cell-cycle mutant cdc21 is a temperature-sensitive thymidylate auxotroph. Molecular & general genetics : MGG 62 794696
2006 Phosphorylation of MCM4 at sites inactivating DNA helicase activity of the MCM4-MCM6-MCM7 complex during Epstein-Barr virus productive replication. Journal of virology 55 17005684
2014 Domain within the helicase subunit Mcm4 integrates multiple kinase signals to control DNA replication initiation and fork progression. Proceedings of the National Academy of Sciences of the United States of America 48 24740181
2003 Thymine-rich single-stranded DNA activates Mcm4/6/7 helicase on Y-fork and bubble-like substrates. The EMBO journal 45 14609960
2021 Celastrol Modulates Multiple Signaling Pathways to Inhibit Proliferation of Pancreatic Cancer via DDIT3 and ATF3 Up-Regulation and RRM2 and MCM4 Down-Regulation. OncoTargets and therapy 44 34194230
2012 Recessive mutations in MCM4/PRKDC cause a novel syndrome involving a primary immunodeficiency and a disorder of DNA repair. Journal of medical genetics 42 22499342
2000 Distinct phosphoisoforms of the Xenopus Mcm4 protein regulate the function of the Mcm complex. Molecular and cellular biology 41 10779356
1998 The promoters for human DNA-PKcs (PRKDC) and MCM4: divergently transcribed genes located at chromosome 8 band q11. Genomics 41 9465298
2020 Antitumor Activity of Ohmyungsamycin A through the Regulation of the Skp2-p27 Axis and MCM4 in Human Colorectal Cancer Cells. Journal of natural products 40 31894983
2006 Site-specific phosphorylation of MCM4 during the cell cycle in mammalian cells. The FEBS journal 38 16519687
1995 Cdc54 belongs to the Cdc46/Mcm3 family of proteins which are essential for initiation of eukaryotic DNA replication. Gene 38 7698653
2012 A dominantly acting murine allele of Mcm4 causes chromosomal abnormalities and promotes tumorigenesis. PLoS genetics 34 23133403
2005 MCM4 expression in esophageal cancer from southern China and its clinical significance. Journal of cancer research and clinical oncology 34 16133572
2019 A conserved Mcm4 motif is required for Mcm2-7 double-hexamer formation and origin DNA unwinding. eLife 33 31385807
2016 Concerted activities of Mcm4, Sld3, and Dbf4 in control of origin activation and DNA replication fork progression. Genome research 27 26733669
2008 Interplay between S-cyclin-dependent kinase and Dbf4-dependent kinase in controlling DNA replication through phosphorylation of yeast Mcm4 N-terminal domain. Molecular biology of the cell 25 18321994
2008 Mcm4 C-terminal domain of MCM helicase prevents excessive formation of single-stranded DNA at stalled replication forks. Proceedings of the National Academy of Sciences of the United States of America 25 18753627
2004 Levels of MCM4 phosphorylation and DNA synthesis in DNA replication block checkpoint control. Journal of structural biology 25 15037254
2011 Widdrol activates DNA damage checkpoint through the signaling Chk2-p53-Cdc25A-p21-MCM4 pathway in HT29 cells. Molecular and cellular biochemistry 23 22160829
2010 C. elegans MCM-4 is a general DNA replication and checkpoint component with an epidermis-specific requirement for growth and viability. Developmental biology 23 21146520
2007 Genetic screen for chromosome instability in mice: Mcm4 and breast cancer. Cell cycle (Georgetown, Tex.) 22 17495541
2005 DNA binding and helicase actions of mouse MCM4/6/7 helicase. Nucleic acids research 20 15917436
2015 G364R mutation of MCM4 detected in human skin cancer cells affects DNA helicase activity of MCM4/6/7 complex. Journal of biochemistry 19 25661590
2010 Increase of Mcm3 and Mcm4 expression in cervical squamous cell carcinomas. European journal of gynaecological oncology 19 21077471
2012 Effect of an MCM4 mutation that causes tumours in mouse on human MCM4/6/7 complex formation. Journal of biochemistry 16 22668557
2015 High expression of carbonic anhydrase IX is significantly associated with glandular lesions in gastroesophageal junction and with tumorigenesis markers BMI1, MCM4 and MCM7. BMC gastroenterology 15 26156831
2012 The Thermococcus kodakaraensis Tko CDC21-1 intein activates its N-terminal splice junction in the absence of a conserved histidine by a compensatory mechanism. Biochemistry 15 22380677
2011 Characterization of Leishmania donovani MCM4: expression patterns and interaction with PCNA. PloS one 15 21829589
2017 An MCM4 mutation detected in cancer cells affects MCM4/6/7 complex formation. Journal of biochemistry 14 27794528
2011 Interaction of heliquinomycin with single-stranded DNA inhibits MCM4/6/7 helicase. Journal of biochemistry 13 22023799
2024 MCM4 potentiates evasion of hepatocellular carcinoma from sorafenib-induced ferroptosis through Nrf2 signaling pathway. International immunopharmacology 12 39276458
2015 HPV-type-specific response of cervical cancer cells to cisplatin after silencing replication licensing factor MCM4. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 12 26188903
2023 EZH2 regulates pancreatic cancer cells through E2F1, GLI1, CDK3, and Mcm4. Hereditas 11 37198697
2001 Identification of an MCM4 homologue expressed specifically in the sexual stage of Plasmodium falciparum. International journal for parasitology 9 11513894
1997 MCM4 and PRKDC, human genes encoding proteins MCM4 and DNA-PKcs, are close neighbours located on chromosome 8q12-->q13. Cytogenetics and cell genetics 9 9284934
2024 Identification of MCM4 and PRKDC as new regulators of osteosarcoma cell dormancy based on 3D cell cultures. Biochimica et biophysica acta. Molecular cell research 8 38216092
2019 Crystal structures of CDC21-1 inteins from hyperthermophilic archaea reveal the selection mechanism for the highly conserved homing endonuclease insertion site. Extremophiles : life under extreme conditions 8 31363851
2025 MCM2-7 ring closure involves the Mcm5 C-terminus and triggers Mcm4 ATP hydrolysis. Nature communications 7 39747125
2021 MCM4 Is a Novel Biomarker Associated With Genomic Instability, BRCAness Phenotype, and Therapeutic Potentials in Soft-Tissue Sarcoma. Frontiers in cell and developmental biology 7 34178990
2018 Function of the amino-terminal region of human MCM4 in helicase activity. Journal of biochemistry 7 30184107
2016 Characterization of a Novel MMS-Sensitive Allele of Schizosaccharomyces pombe mcm4. G3 (Bethesda, Md.) 6 27473316
2015 c-ETS transcription factors play an essential role in the licensing of human MCM4 origin of replication. Biochimica et biophysica acta 6 26365772
2010 The effects of oligomerization on Saccharomyces cerevisiae Mcm4/6/7 function. BMC biochemistry 6 20860810
2007 [Expression and significance of MCM4 in esophageal cancer]. Ai zheng = Aizheng = Chinese journal of cancer 6 17222376
2025 Celastrol promotes DNA damage and apoptosis in uterine corpus endometrial carcinoma via promotion of KAT2B-mediated RBPJ acetylation and repression of MCM4 transcription. Molecular medicine (Cambridge, Mass.) 5 39901144
2020 Effect of the natural compound trans‑resveratrol on human MCM4 gene transcription. Oncology reports 5 32377740
2004 MCM4 shares homology to a replication/DNA-binding domain in CTF and is contacted by pRb. Biochemical and biophysical research communications 5 15081408
2020 Active Replication Checkpoint Drives Genome Instability in Fission Yeast mcm4 Mutant. Molecular and cellular biology 4 32341083
2025 Transcription factor E2F1 promotes non-small cell lung cancer progression by activating the PI3K/AKT pathway through MCM4. Journal of cardiothoracic surgery 3 40437556
2024 MCM4 Promotes the Progression of Malignant Melanoma by Activating the PI3K/AKT Pathway. Environmental toxicology 3 39501995
2013 Expression, purification and biochemical characterization of Schizosaccharomyces pombe Mcm4, 6 and 7. BMC biochemistry 3 23444842
2025 E2F7 upregulates MCM4 and fatty acid metabolism to advance lung adenocarcinoma metastasis. Prostaglandins & other lipid mediators 2 40158794
2023 E2F2 is upregulated by the ERK pathway and regulates decidualization via MCM4. Gene 2 37028609
2007 The promoter regions of the Myb-regulated Adora2B and Mcm4 genes co-localize with origins of DNA replication. BMC molecular biology 2 17822556
2025 MCM4 as Potential Metastatic Biomarker in Lung Adenocarcinoma. Diagnostics (Basel, Switzerland) 1 40564876
2026 Expression of MCM2, MCM4, and MCM10 in hepatocellular carcinoma based on bioinformatic analyses and their predictive value for postoperative recurrence: An initial model development study. Surgical oncology 0 41921256
2026 The CDK4/6 inhibitor dalpiciclib augments the antitumor efficacy of enzalutamide in preclinical models of castration-resistant prostate cancer through inhibition of MCM4-mediated DNA replication. Cell death & disease 0 42248826
2025 Promotion of Melanoma Progression through MCM4-Induced Immune Suppression and Polarization of Macrophages by Carcinogenic Exosomes. Current cancer drug targets 0 40375706
2025 Comprehensive analysis reveals MCM4 as a biomarker for guiding therapies and immunomodulatory role in skin cutaneous melanoma. Journal of Cancer 0 40959096
2025 Integrative Multi-Omics and Functional Characterization Reveal MCM4 as a Key Oncogenic Regulator in Hepatocellular Carcinoma. OncoTargets and therapy 0 41333157

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