Affinage

MYT1

Myelin transcription factor 1 · UniProt Q01538

Length
1121 aa
Mass
122.3 kDa
Annotated
2026-06-10
84 papers in source corpus 35 papers cited in narrative 35 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

The MYT1 locus encodes two functionally distinct activities documented in this corpus: a membrane-associated cell-cycle kinase and a neural zinc-finger transcriptional repressor. As a kinase, MYT1 is a Wee1-family dual-specificity enzyme that preferentially phosphorylates CDK1/Cdc2 on Thr14 (and Tyr15) in a cyclin-dependent manner to inhibit Cdc2/cyclin B and restrain mitotic entry (PMID:7569953, PMID:9001210, PMID:9268380). It is anchored to the endoplasmic reticulum and Golgi through a C-terminal hydrophobic membrane-targeting domain, whose removal redirects the protein to the nucleus (PMID:9001210); a distinct C-terminal segment both binds Cdc2/cyclin B1 and supports cytoplasmic sequestration of the complex, so MYT1 enforces G2/M arrest by phosphorylation and by physical sequestration (PMID:10504341, PMID:10373560). MYT1 is inactivated at M phase by a multi-kinase program: CDK1/XRINGO-mediated phosphorylation lowers activity and licenses p90Rsk docking, after which p90Rsk hyperphosphorylates the C-terminus and abolishes CDK1/cyclin B binding (PMID:18951089, PMID:20362450), with parallel inhibitory input from Plk1/Plx1 (via a Cdc2-created Thr478 docking site), Akt, SGK, and MEK1 (PMID:12738781, PMID:15692562, PMID:11802161, PMID:31537708, PMID:23241949). Beyond preventing premature mitosis, MYT1-mediated Cdc2 suppression is required for Golgi/ER reassembly during mitotic exit, contributes to DNA-damage checkpoint recovery, and is functionally redundant with Wee1 such that elevated MYT1 confers resistance to Wee1/CHK1/ATR inhibitors (PMID:18378775, PMID:23146904, PMID:31594837, PMID:38020882). The neural MYT1 is a transcriptional repressor that recruits HDAC-containing Sin3B and LSD1/CoREST complexes to repress non-neuronal and progenitor genes, counteracts Notch signaling to drive neuronal differentiation, and represses YAP1 and retinoic-acid receptor genes (PMID:15935060, PMID:24828497, PMID:27705795, PMID:32251364, PMID:30312684). Loss-of-function MYT1 variants associated with oculo-auriculo-vertebral spectrum (OAVS) fail to downregulate RA receptor expression, linking MYT1 to this developmental disorder through the retinoic-acid signaling pathway (PMID:27358179, PMID:28612832).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1995 High

    Established the founding biochemical identity of MYT1: what enzyme provides Thr14-directed inhibition of Cdc2 was unknown, and this work identified a membrane-associated Wee1-family kinase as the predominant Thr14 kinase regulating the cell cycle.

    Evidence cDNA cloning, in vitro kinase assay, and immunodepletion of Xenopus egg extracts

    PMID:7569953

    Open questions at the time
    • Membrane anchor and its targeting domain not yet mapped
    • Human ortholog substrate preference not yet defined
  2. 1997 High

    Defined the human enzyme's substrate selectivity and subcellular address, showing MYT1 is a dual-specificity kinase preferring Thr14 on Cdc2 and is tethered to the ER/Golgi by a C-terminal hydrophobic domain.

    Evidence cDNA cloning, in vitro kinase assays with site mapping, immunofluorescence, and deletion mutagenesis in HeLa cells

    PMID:9001210 PMID:9268380

    Open questions at the time
    • Mechanism of M-phase hyperphosphorylation/inactivation not defined
    • Upstream regulatory kinases unidentified
  3. 1999 High

    Resolved how MYT1 enforces arrest beyond catalysis, showing the C-terminal 63-residue domain binds Cdc2/cyclin B1 and that MYT1 blocks cyclin B1 nuclear shuttling and arrests cells independent of catalytic activity.

    Evidence Deletion mutagenesis, kinase-dead overexpression, cyclin B1 localization imaging, and cell cycle analysis in fission yeast and human cells

    PMID:10373560 PMID:10504341

    Open questions at the time
    • Physiological balance between catalytic vs sequestration roles unquantified
  4. 2002 Medium

    Began mapping the kinase network that switches MYT1 off at the G2/M transition, identifying MYT1 as a substrate of Akt and of Mos during oocyte/meiotic maturation.

    Evidence In vitro kinase assays, co-IP, and oocyte microinjection in starfish and Xenopus

    PMID:11802161 PMID:11959823

    Open questions at the time
    • Mos result is a single-lab Co-IP plus in vivo phosphorylation without site mapping
    • Direct vs indirect Akt action on MYT1 in somatic cells unclear
  5. 2005 High

    Distinguished context-specific inactivation pathways, showing p90Rsk down-regulates MYT1 in meiosis whereas a Cdc2-primed Thr478 docking site recruits Plx1 to inhibit MYT1 in the embryonic cell cycle.

    Evidence GST pulldown, reciprocal co-IP, in vitro kinase assays, Thr478 mutagenesis, and embryo microinjection (Xenopus)

    PMID:15692562 PMID:9724639

    Open questions at the time
    • Quantitative contribution of each kinase to net MYT1 inactivation not resolved
  6. 2003 High

    Extended the inhibitory kinase set and identified a positive regulator, establishing MYT1 as a Plk1 substrate at four consensus C-terminal sites and TSAP6 as a physical interactor that augments MYT1 activity.

    Evidence In vitro kinase assays with 4A mutant and mobility shifts; yeast two-hybrid, GST pulldown, and co-IP for TSAP6

    PMID:12606722 PMID:12738781

    Open questions at the time
    • TSAP6 mechanism of activation undefined and Medium-confidence
    • In vivo consequence of Plk1 sites on mitotic timing not isolated
  7. 2006 Medium

    Identified an intramolecular priming event, showing MYT1 autophosphorylation on Ser66 is a prerequisite/trigger for subsequent inhibitory phosphorylation during the meiotic G2/M transition.

    Evidence MALDI mass spectrometry site identification and S66A/S76A mutagenesis with oocyte cell-cycle timing

    PMID:16481744

    Open questions at the time
    • Single lab; autophosphorylation kinetics in somatic mitosis untested
  8. 2008 High

    Delineated the ordered two-step inactivation and a non-cell-cycle organelle role, showing CDK/XRINGO phosphorylates three regulatory serines distinct from CDK/cyclin sites, and that MYT1 is required for Golgi/ER reassembly at mitotic exit via cyclin B targeting.

    Evidence In vitro kinase assays with site mapping and mutagenesis (Xenopus); siRNA knockdown with Golgi/ER imaging and cyclin B1/B2 epistasis (mammalian cells)

    PMID:18378775 PMID:18951089

    Open questions at the time
    • How membrane-tethered MYT1 locally couples Cdc2 suppression to organelle dynamics not mechanistically resolved
  9. 2005 High

    Opened the transcription-factor branch of MYT1 biology, showing MYT1 binds Sin3B and recruits HDAC1/HDAC2 to repress a heterologous promoter.

    Evidence Yeast and mammalian two-hybrid, co-IP, and reporter assays

    PMID:15935060

    Open questions at the time
    • Endogenous target genes of the MYT1-Sin3B-HDAC complex not yet identified
  10. 2009 High

    Linked MYT1 to stress-induced apoptosis, showing JNK1 (not JNK2) binds and phosphorylates MYT1 and that MYT1 is required for UVA-induced caspase-3 cleavage and DNA fragmentation.

    Evidence Co-IP, in vitro kinase assays, JNK1/JNK2 knockout fibroblasts, MYT1 siRNA, and apoptosis readouts

    PMID:19204086

    Open questions at the time
    • Mechanistic link between MYT1 phosphorylation and apoptotic execution undefined
  11. 2010 High

    Established that compartmentalization is functionally essential and refined the meiotic two-step model, showing cytoplasmic MYT1 must be down-regulated for meiotic resumption and that CDK1/XRINGO priming both reduces activity and recruits p90Rsk, which then abolishes CDK1/cyclin B binding.

    Evidence siRNA and forced-mislocalization in mouse oocytes; site mapping, mutagenesis, co-IP, and microinjection in Xenopus

    PMID:20083600 PMID:20362450

    Open questions at the time
    • How localization is dynamically controlled in somatic mitosis not addressed
  12. 2012 High

    Connected MYT1 to additional mitotic-entry inputs and the DNA-damage response, showing MEK1-dependent phosphorylation inactivates MYT1 to permit Golgi fragmentation/mitotic entry and that MYT1 contributes specifically to checkpoint recovery by raising the CDK1 activation threshold.

    Evidence siRNA epistasis with MEK1 inhibition and permeabilized-cell Golgi assays; time-lapse with CHK1/WEE1 inhibitors and xenografts

    PMID:23146904 PMID:23241949

    Open questions at the time
    • The MEK1-dependent intermediary kinase (independent of RSK/Plk/CDK1) unidentified
    • MYT1 dispensable for checkpoint activation/normal cycling — role bounded to recovery
  13. 2014 High

    Defined the neural epigenetic repressor mechanism, showing MYT1 is a stable subunit of a neural LSD1 complex that directly represses Pten and supports neuroblastoma proliferation.

    Evidence Biochemical purification, co-IP, ChIP, microarray, and siRNA proliferation assays in Neuro2a cells

    PMID:24828497

    Open questions at the time
    • Stoichiometry and recruitment determinants of MYT1 within the LSD1 complex not defined
  14. 2016 High

    Placed MYT1 in neuronal differentiation and developmental disease, showing genome-wide MYT1 binding represses Notch pathway genes to drive neurogenesis and that OAVS-associated variants fail to repress RA receptor expression.

    Evidence ChIP-seq, overexpression/knockdown with Notch epistasis; MYT1 wild-type vs OAVS-mutant RARB assays and zebrafish myt1a knockdown

    PMID:27170181 PMID:27358179 PMID:27705795

    Open questions at the time
    • Direct vs indirect repression of individual Notch/RA targets not all resolved
    • Drosophila spermatocyte data implicate Cyclin A/Cdk1 rather than the transcription-factor role — two activities not unified
  15. 2018 Medium

    Identified anti-proliferative transcriptional targets in glioblastoma, showing DNA-targeted MYT1 represses transcription and that MYT1/MYT1L directly repress YAP1, whose forced expression rescues proliferation.

    Evidence Reporter assays, genome-wide RNA-seq, YAP1 rescue, and orthotopic xenografts in GBM cells

    PMID:29291346 PMID:30312684

    Open questions at the time
    • Single-lab functional epistasis; direct MYT1 occupancy at the YAP1 locus not shown
    • Distinction of MYT1 vs MYT1L contributions incomplete
  16. 2017 Medium

    Strengthened the MYT1-retinoic-acid link in OAVS, showing MYT1 overexpression downregulates RARA/RARB/RARG and a novel OAVS missense variant perturbs this regulation.

    Evidence Overexpression with wild-type vs mutant comparison and RT-PCR of RA pathway genes

    PMID:28612832

    Open questions at the time
    • Single method, single lab; whether RAR repression is direct unknown
  17. 2019 Medium

    Established therapeutic relevance and redundancy, showing MYT1 and Wee1 redundantly inhibit Cdk1/cyclin B and that elevated MYT1 confers Wee1-inhibitor resistance reversible by MYT1 knockdown; SGK was added as another inhibitory upstream kinase.

    Evidence MYT1 overexpression/knockdown with Cdk1 activity and adavosertib sensitivity assays; in vitro kinase and starfish oocyte assays for SGK

    PMID:31537708 PMID:31594837

    Open questions at the time
    • Mechanistic basis of redundancy (shared vs distinct CDK1 pools) not defined
    • SGK data single-lab oocyte system
  18. 2019 Medium

    Extended the neural repressor mechanism across species, showing the C. elegans homolog ZTF-11 acts with the MuvB corepressor to suppress non-neuronal genes and is sufficient to drive ectopic neurogenesis.

    Evidence Loss- and gain-of-function with MuvB co-function analysis and single-cell expression profiling in C. elegans

    PMID:31386623

    Open questions at the time
    • Conservation of MuvB partnership in mammalian MYT1 untested
  19. 2020 Medium

    Broadened tissue contexts for both MYT1 activities, linking the transcription factor to LSD1/CoREST-dependent neuroblastoma differentiation, NSC aging via SMAD-driven activation, and the kinase to Drosophila enteroblast differentiation through Cyclin A/Cdk1 inhibition.

    Evidence Co-IP and LSD1-inhibitor epistasis (neuroblastoma); shRNA and pathway dissection (NSC); null mutants/RNAi with Cyclin A epistasis (Drosophila midgut)

    PMID:32251364 PMID:33038325 PMID:33207203

    Open questions at the time
    • Each context is single-lab
    • How a single locus partitions kinase vs transcription-factor functions across cell types unresolved
  20. 2021 Medium

    Refined the inactivation map to the N-terminus, showing the PAYF motif and CDK1 sites Thr11/Thr16 contribute to MYT1 inactivation during M phase alongside C-terminal regulation.

    Evidence Site-directed mutagenesis and in vivo phosphorylation analysis in Xenopus oocytes

    PMID:34695617

    Open questions at the time
    • Single lab/study
    • Relative weight of N- vs C-terminal regulation not quantified
  21. 2023 Medium

    Consolidated MYT1 as a multi-checkpoint resistance node, showing MYT1 overexpression compensates for CDK1 inhibition to confer resistance to Wee1, CHK1, and ATR inhibitors.

    Evidence Overexpression with multiple kinase inhibitors, time-lapse mitotic-entry assays, and clonogenic survival

    PMID:38020882

    Open questions at the time
    • Single lab; clinical predictive value untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single MYT1 locus produces and partitions two biochemically unrelated activities — a membrane-tethered CDK1-inhibitory kinase and a nuclear zinc-finger repressor — across cell types, and whether these activities ever co-regulate one another in the same cell.
  • No isoform-resolved expression map linking kinase vs TF outputs
  • No structural model of either MYT1 activity in the corpus
  • Direct MYT1 occupancy at most reported target loci not demonstrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0140110 transcription regulator activity 5 GO:0016740 transferase activity 4 GO:0140313 molecular sequestering activity 2
Localization
GO:0005634 nucleus 3 GO:0005794 Golgi apparatus 3 GO:0005829 cytosol 3 GO:0005783 endoplasmic reticulum 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-1640170 Cell Cycle 6 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1266738 Developmental Biology 4 R-HSA-1474165 Reproduction 4 R-HSA-4839726 Chromatin organization 3 R-HSA-5357801 Programmed Cell Death 1
Partners
CCNB1CDK1KDM1A (LSD1)MAPK8 (JNK1)PLK1RPS6KA (P90RSK)SIN3BTSAP6
Complex memberships
LSD1/CoREST complexSin3B-HDAC1/HDAC2 complex

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Xenopus Myt1 is a membrane-associated kinase of the Wee1 family that phosphorylates Cdc2 on both Thr14 and Tyr15, making it the predominant Thr14-specific kinase in Xenopus egg extracts; it contains a putative transmembrane segment mediating membrane association, and its activity is highly regulated during the cell cycle. cDNA cloning, in vitro kinase assay, immunodepletion of Xenopus egg extracts Science High 7569953
1997 Human Myt1 (Myt1Hu) is a dual-specificity kinase that preferentially phosphorylates Cdc2 on Thr14 (over Tyr15) in a cyclin-dependent manner; it localizes to the endoplasmic reticulum and Golgi complex in HeLa cells via a hydrophobic C-terminal membrane-targeting domain, deletion of which redirects Myt1 to the nucleus. cDNA cloning, in vitro kinase assay with phosphorylation-site mapping, immunofluorescence localization, deletion mutagenesis Molecular and cellular biology High 9001210
1997 Human Myt1 specifically phosphorylates and inactivates Cdc2-containing cyclin complexes but not Cdk2- or Cdk4-containing complexes; Myt1 remains membrane-bound throughout the cell cycle but becomes hyperphosphorylated and less active during M-phase arrest; Cdc2/cyclin B1 can phosphorylate Myt1 in vitro without affecting its kinase activity. In vitro kinase assay with substrate specificity panel, immunoprecipitation, cell cycle synchronization, Western blot The Journal of biological chemistry High 9268380
1998 The C-terminal regulatory domain of Xenopus Myt1 specifically binds p90rsk (a MAPK-activated kinase); p90rsk phosphorylates the Myt1 C-terminus and down-regulates its inhibitory activity on Cdc2/cyclin B in vitro; Myt1 preferentially associates with hyperphosphorylated p90rsk, and complexes are detected in immunoprecipitates from mature Xenopus oocytes, linking MAPK-p90rsk signaling to Myt1 inactivation during oocyte maturation. GST pulldown, co-immunoprecipitation from oocyte extracts, in vitro kinase assay The EMBO journal High 9724639
1999 The C-terminal domain of Myt1 is required for: (1) interaction with Cdc2/cyclin B1 complexes, (2) efficient phosphorylation of Cdc2 in vitro, and (3) G2/M phase arrest upon Myt1 overexpression; the C-terminal domain interacts with and is phosphorylated by Cdc2, indicating cytoplasmic localization of this domain; Myt1 can inhibit cell cycle progression both by phosphorylating Cdc2 and by sequestering Cdc2/cyclin B1 complexes in the cytoplasm. Overexpression in S. pombe and human osteosarcoma cells, C-terminal truncation mutants, in vitro kinase assay, co-immunoprecipitation, cell cycle analysis Journal of cell science High 10504341
1999 Overproduction of either kinase-active or kinase-inactive Myt1 blocks nuclear-cytoplasmic shuttling of cyclin B1 and causes G2 delay; the COOH-terminal 63 amino acids of Myt1 constitute a Cdc2/cyclin B1 interaction domain required for cyclin B1 binding and efficient Cdc2 phosphorylation; Myt1 lacking this domain does not sequester Cdc2/cyclin B1 or perturb cell cycle progression. Overexpression of kinase-active and kinase-inactive mutants, deletion mutagenesis, in vitro kinase assay, live-cell imaging/localization of cyclin B1, cell cycle analysis Molecular and cellular biology High 10373560
2002 Akt/PKB phosphorylates and downregulates Myt1 (a Wee1 family member) in starfish oocytes, switching the balance between Cdc25 and Wee1/Myt1 activities and causing initial activation of cyclin B-Cdc2 at the meiotic G2/M transition, identifying Myt1 as a new Akt substrate and Akt as an M-phase initiator. In vitro kinase assay, phosphorylation-site analysis, oocyte microinjection, biochemical fractionation Nature cell biology High 11802161
2002 Mos interacts with Myt1 in Xenopus oocyte extracts and triggers Myt1 phosphorylation on certain sites in vivo independently of MAPK activation, suggesting Myt1 is a direct Mos target in the MPF activation pathway during meiotic resumption. Co-immunoprecipitation from oocyte extracts, in vivo phosphorylation analysis, MAPK-independent oocyte maturation assays Development Medium 11959823
2003 Plk1 phosphorylates Myt1 in vitro on four C-terminal sites matching a newly defined Plk1 consensus motif (hydrophobic at +1, acidic at −2); a Myt1-4A mutant (all four sites alanine) abolishes Plk1 phosphorylation in vitro and fails to show mitotic gel-mobility shift in nocodazole-arrested cells, establishing Myt1 as a Plk1 substrate during M phase. In vitro kinase assay with consensus motif-defined peptides, site-directed mutagenesis (4A mutant), SDS-PAGE mobility-shift analysis in nocodazole-arrested cells The Journal of biological chemistry High 12738781
2003 TSAP6 (a p53-inducible transmembrane protein) associates physically with the Myt1 kinase as demonstrated by yeast two-hybrid, GST pulldown, and co-immunoprecipitation; TSAP6 overexpression augments Myt1 activity. Yeast two-hybrid, GST/in vitro pulldown, co-immunoprecipitation, cell cycle analysis Proceedings of the National Academy of Sciences Medium 12606722
2005 The Polo-like kinase Plx1 interacts with and inhibits Myt1 after fertilization of Xenopus eggs; Cdc2 phosphorylates Myt1 on Thr478 at M phase, creating a docking site for Plx1; Plx1 phosphorylates Myt1 and inhibits its kinase activity both in vitro and in vivo; this Plx1-Myt1 interaction replaces p90rsk-Myt1 interaction seen in meiosis, and is required for normal embryonic cell divisions. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis (Thr478), in vivo embryo microinjection experiments The EMBO journal High 15692562
2005 Myt1 and Myt1L interact with Sin3B via a protein-protein interaction domain; Myt1-Sin3B complexes include HDAC1 and HDAC2 as demonstrated by co-immunoprecipitation from transfected mammalian cells; Myt1/Myt1L interaction with the HDAC-binding isoform of Sin3B confers repression on a heterologous promoter, placing Myt1 as a transcriptional repressor through HDAC recruitment. Yeast two-hybrid, mammalian two-hybrid, co-immunoprecipitation, transcriptional reporter assay Journal of neurochemistry High 15935060
2008 Xenopus Myt1 is inactivated by CDK/XRINGO-mediated phosphorylation on three specific serine residues in its regulatory domain that are distinct from CDK/cyclin phosphorylation sites; mutation of these serines makes Myt1 resistant to CDK/XRINGO-mediated inhibition; CDK/XRINGO thus has substrate specificity different from CDK/cyclin complexes. In vitro kinase assay, site-directed mutagenesis, phosphorylation-site mapping, Xenopus oocyte functional assays Molecular cell High 18951089
2008 Myt1 is essential for Golgi and ER assembly during telophase (mitotic exit) in mammalian cells; both cyclin B1 and cyclin B2 serve as Myt1 targets for proper organelle reassembly; Myt1-mediated Cdc2 suppression is specifically required for control of intracellular membrane dynamics during mitosis. siRNA knockdown of Myt1 in mammalian cells, immunofluorescence of Golgi/ER markers, epistasis with cyclin B1/B2 depletion The Journal of cell biology High 18378775
2009 JNK1 (but not JNK2) interacts with and phosphorylates Myt1 ex vivo and in vitro; JNK1-deficient cells show suppressed Myt1 phosphorylation and reduced caspase-3 cleavage upon UVA irradiation; JNK2-deficient cells show increased Myt1 phosphorylation and caspase-3 cleavage; knockdown of Myt1 suppresses UVA-induced caspase-3 cleavage and DNA fragmentation, indicating JNK1-mediated Myt1 phosphorylation promotes UVA-induced apoptosis. Co-immunoprecipitation, in vitro kinase assay, JNK1/JNK2 knockout fibroblasts, Myt1 siRNA knockdown, caspase-3 cleavage assay, Xenopus overexpression Molecular and cellular biology High 19204086
2010 In mouse oocytes, both Wee1B (nuclear) and Myt1 (cytoplasmic) must be downregulated for meiotic resumption; mislocalized Wee1B or Myt1 (forced into wrong compartment) cannot maintain meiotic arrest, demonstrating that compartment-specific localization is functionally required; Cdc25B translocation from cytoplasm to nucleus and Wee1B export from nucleus to cytoplasm before GV breakdown are regulated by PKA inactivation and MPF activation respectively. siRNA knockdown of Wee1B and/or Myt1 in mouse oocytes, forced mislocalization constructs, live imaging, cell cycle analysis The Journal of cell biology High 20083600
2010 Myt1 inactivation during Xenopus oocyte maturation proceeds in two steps: early CDK1/XRINGO-mediated phosphorylation reduces Myt1 activity AND facilitates docking/recruitment of p90Rsk; five p90Rsk phosphorylation sites on Myt1 (distinct from CDK1/XRINGO sites) were identified; mutation of these five sites impairs Myt1 hyperphosphorylation and makes it resistant to p90Rsk inhibition; p90Rsk-phosphorylated Myt1 does not interact with CDK1/cyclin B, preventing further CDK1 inhibition after meiosis I entry. In vitro kinase assay, phosphorylation-site mapping, site-directed mutagenesis, Xenopus oocyte microinjection, co-immunoprecipitation Current biology High 20362450
2012 MEK1 phosphorylates and inactivates Myt1 to promote Golgi fragmentation in G2 and mitotic entry; Myt1 knockdown by siRNA increases efficiency of Golgi fragmentation by mitotic cytosol and eliminates the requirement for MEK1 in Golgi fragmentation and mitotic entry; MEK1-dependent phosphorylation of Myt1 requires another kinase but is independent of RSK, Plk, and CDK1. siRNA knockdown of Myt1, permeabilized cell Golgi fragmentation assay, MEK1 inhibition, epistasis analysis The EMBO journal High 23241949
2012 MYT1 contributes to DNA damage checkpoint recovery but not to checkpoint activation or normal cell cycle progression; depletion of MYT1 causes precocious mitotic entry when the checkpoint is abrogated with CHK1 or WEE1 inhibitors; MYT1 kinase activity is high during checkpoint activation and reduced during checkpoint recovery; MYT1 depletion lowers the threshold for CDK1 activation. siRNA depletion, time-lapse microscopy, CHK1/WEE1 inhibitor treatment, CDK1 activity assays, clonogenic survival, tumor xenograft models Oncogene High 23146904
2014 MyT1 is identified as a component of a neural cell type-specific LSD1 complex; MyT1 forms a stable multiprotein complex with LSD1 through direct interaction; the LSD1-MyT1 complex directly regulates the Pten gene as revealed by microarray and ChIP assays; knockdown of either LSD1 or MyT1 derepresses target gene expression and inhibits proliferation of Neuro2a neuroblastoma cells. Biochemical purification of LSD1 complex from neural cells, co-immunoprecipitation, ChIP assay, microarray, siRNA knockdown with proliferation assay The Journal of biological chemistry High 24828497
2016 MyT1 promotes neuronal differentiation by counteracting Notch signaling; MyT1 binding is associated with transcriptional repression in neural progenitor cells; MyT1 targets include the Notch1 receptor and downstream targets including Hes1, Sox2, Id3, and Olig1 (regulators of the neural progenitor program), establishing Ascl1-induced MyT1 as a cell-autonomous suppressor of Notch signaling. Functional overexpression/knockdown in neurogenesis models, genome-wide ChIP-seq for MyT1 binding, transcriptional profiling, epistasis with Notch signaling components Cell reports High 27705795
2018 When targeted to DNA via its consensus binding site, Myt1 represses transcription (whereas Myt1l activates); genome-wide analyses in a GBM cell line show largely overlapping effects of Myt1 and Myt1l on endogenous gene expression; an activation function in Myt1l maps to a poorly conserved N-terminal region absent in Myt1. Luciferase reporter assay with heterologous DNA-binding domain fusion, genome-wide RNA-seq, domain mapping by truncation Journal of cellular biochemistry Medium 29291346
2018 Myt1 and Myt1l directly repress expression of YAP1 (a Hippo pathway coactivator) in GBM cells; overexpression of YAP1 overcomes the anti-proliferative effect of Myt1/Myt1l; reducing YAP1 expression slows orthotopic tumor xenograft growth, establishing YAP1 repression as a functional mechanism of Myt1-mediated anti-proliferative activity. Re-expression of Myt1/Myt1l in GBM cell lines, gene expression analysis, YAP1 overexpression/knockdown rescue experiments, orthotopic xenograft models Biochimica et biophysica acta. Gene regulatory mechanisms Medium 30312684
2019 Myt1 and Wee1 kinases are both capable of phosphorylating and inhibiting Cdk1/cyclin B; cancer cells with elevated Myt1 have acquired resistance to the Wee1 inhibitor adavosertib; downregulating Myt1 in resistant cells enhances ectopic Cdk1 activity and restores sensitivity to adavosertib, demonstrating functional redundancy between Myt1 and Wee1 for Cdk1 inhibition. Myt1 overexpression/knockdown, Cdk1 activity assays, adavosertib treatment, cell viability assays Cancer research Medium 31594837
2019 SGK directly phosphorylates both Cdc25 and Myt1 to trigger cyclin B-Cdk1 activation at the meiotic G2/M transition in starfish oocytes; SGK activation requires cooperation between Gβγ-PI3K and an atypical Gβγ pathway downstream of hormonal stimulation. In vitro kinase assay, starfish oocyte microinjection, phosphorylation-site analysis, inhibitor/dominant-negative approaches The Journal of cell biology Medium 31537708
2020 MYT1 (transcription factor) interacts physically with the LSD1/CoREST complex in neuroblastoma cells; MYT1 knockdown inhibits proliferation and promotes differentiation; depletion of LSD1 or inhibition of LSD1 by ORY-1001 decreases MYT1 expression; many MYT1-regulated differentiation genes are targets of the REST complex. Co-immunoprecipitation, siRNA knockdown, omics target gene analysis, LSD1 inhibitor treatment, differentiation/proliferation assays Oncogene Medium 32251364
2020 SMAD4 and SMAD5 (transferred via ESC-derived extracellular vesicles) activate MYT1 transcription in neural stem cells; MYT1 in turn downregulates Egln3, leading to activation of HIF-2α, NAMPT, and Sirt1 sequentially; MYT1 knockdown in young NSCs accelerates aging phenotypes and impairs proliferation and differentiation. Transcriptome analysis, shRNA knockdown of MYT1, SMAD4/5 overexpression, ESC-sEV treatment, pathway inhibition assays Molecular therapy Medium 33038325
2021 The N-terminal region of Xenopus Myt1, specifically the PAYF motif and adjacent CDK1 phosphorylation sites (Thr11 and Thr16), is required for normal Myt1 activity in oocytes; CDK1-mediated phosphorylation at these N-terminal sites contributes to Myt1 inactivation during M phase, in addition to the previously characterized C-terminal regulation. Site-directed mutagenesis, Xenopus oocyte microinjection, in vivo phosphorylation analysis Cells & development Medium 34695617
2006 Myt1 autophosphorylates on Ser66 and Ser76 (identified by MALDI mass spectrometry); the Ser66Ala mutant of Xenopus Myt1 is more potent at delaying meiosis entry and is hypophosphorylated (loss of mobility shift), indicating that autophosphorylation of Ser66 is a prerequisite and/or trigger for subsequent phosphorylation and inactivation of Myt1 during meiotic G2/M transition. MALDI mass spectrometry phospho-site identification, site-directed mutagenesis (S66A, S76A), Xenopus oocyte microinjection and cell cycle timing Cell cycle Medium 16481744
2016 In Drosophila spermatocytes, Myt1 inhibition of Cyclin A/Cdk1 (not Cyclin B/Cdk1) is essential for fusome integrity and centriole engagement during premeiotic G2 arrest; loss of Myt1 activity causes disrupted intercellular bridges and premature centriole disengagement leading to multipolar spindles; these defects are suppressed by depletion of Cyclin A or ectopic Wee1 expression. Drosophila myt1 null mutants, genetic epistasis with cyclin A depletion and Wee1 overexpression, Cdk1F phosphorylation-defective mutant phenocopying Molecular biology of the cell High 27170181
2020 In Drosophila midgut, Myt1 depletion alters cell cycle kinetics and promotes ectopic mitoses of enteroblast progenitors at the expense of differentiation; these aberrant enteroblast mitoses rely on Cyclin A, implicating Myt1 inhibition of Cyclin A/Cdk1 as the mechanism coupling mitotic exit with enteroblast-to-enterocyte differentiation. myt1 null mutants, cell-specific RNAi, genetic epistasis with Cyclin A depletion, cell cycle and differentiation marker analysis Cell reports Medium 33207203
2023 Myt1 overexpression confers resistance to inhibitors of Wee1 (adavosertib/PD166285), CHK1 (UCN-01), and ATR (AZD6738) by compensating for CDK1 inhibition; Myt1 overexpression reduces premature mitotic entry and decreases mitosis length, increasing survival in checkpoint-abrogated cells. Myt1 overexpression, kinase inhibitor treatment, mitotic entry assays (time-lapse), clonogenic survival assays Frontiers in cell and developmental biology Medium 38020882
2016 MYT1 overexpression in cells downregulates retinoic acid receptor beta (RARB) expression, whereas OAVS-associated MYT1 mutants fail to do so, placing MYT1 in the retinoic acid signaling pathway and demonstrating loss-of-function consequences for OAVS-associated variants. MYT1 overexpression in cell culture, RARB expression analysis, comparison of wild-type vs. mutant MYT1, zebrafish morpholino knockdown of myt1a Journal of medical genetics Medium 27358179
2017 MYT1 overexpression downregulates all RA receptor genes (RARA, RARB, RARG) but not CYP26A1; a novel OAVS-associated MYT1 missense variant (p.Ser108Leu) impacts the expression of RA receptor genes, further supporting MYT1 function in the RA signaling pathway. MYT1 overexpression, wild-type vs. mutant comparison, RT-PCR quantification of RA pathway genes European journal of human genetics Medium 28612832
2019 ZTF-11 (C. elegans Myt1 homolog) functions together with the MuvB corepressor complex to suppress activation of non-neuronal genes in neurons; loss of ztf-11 leads to upregulation of non-neuronal genes and reduced neurogenesis; ectopic expression of ztf-11 in epidermal lineages is sufficient to produce additional neurons. ztf-11 loss-of-function, ectopic expression, MuvB complex co-function analysis, single-cell resolution expression profiling eLife Medium 31386623

Source papers

Stage 0 corpus · 84 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Myt1: a membrane-associated inhibitory kinase that phosphorylates Cdc2 on both threonine-14 and tyrosine-15. Science (New York, N.Y.) 580 7569953
1997 The human Myt1 kinase preferentially phosphorylates Cdc2 on threonine 14 and localizes to the endoplasmic reticulum and Golgi complex. Molecular and cellular biology 297 9001210
1998 A link between MAP kinase and p34(cdc2)/cyclin B during oocyte maturation: p90(rsk) phosphorylates and inactivates the p34(cdc2) inhibitory kinase Myt1. The EMBO journal 296 9724639
2003 Identification of a consensus motif for Plk (Polo-like kinase) phosphorylation reveals Myt1 as a Plk1 substrate. The Journal of biological chemistry 282 12738781
1997 Human Myt1 is a cell cycle-regulated kinase that inhibits Cdc2 but not Cdk2 activity. The Journal of biological chemistry 246 9268380
1996 X-MyT1, a Xenopus C2HC-type zinc finger protein with a regulatory function in neuronal differentiation. Cell 203 8980226
2002 Akt inhibits Myt1 in the signalling pathway that leads to meiotic G2/M-phase transition. Nature cell biology 175 11802161
1999 The C-terminal domain of the Cdc2 inhibitory kinase Myt1 interacts with Cdc2 complexes and is required for inhibition of G(2)/M progression. Journal of cell science 139 10504341
2010 Wee1B, Myt1, and Cdc25 function in distinct compartments of the mouse oocyte to control meiotic resumption. The Journal of cell biology 125 20083600
2004 Knockdown of Chk1, Wee1 and Myt1 by RNA interference abrogates G2 checkpoint and induces apoptosis. Cancer biology & therapy 118 14726685
1999 Overproduction of human Myt1 kinase induces a G2 cell cycle delay by interfering with the intracellular trafficking of Cdc2-cyclin B1 complexes. Molecular and cellular biology 103 10373560
2005 Myt1 family recruits histone deacetylase to regulate neural transcription. Journal of neurochemistry 101 15935060
1997 Myelin transcription factor 1 (Myt1) of the oligodendrocyte lineage, along with a closely related CCHC zinc finger, is expressed in developing neurons in the mammalian central nervous system. Journal of neuroscience research 96 9373037
2003 The p53-inducible TSAP6 gene product regulates apoptosis and the cell cycle and interacts with Nix and the Myt1 kinase. Proceedings of the National Academy of Sciences of the United States of America 95 12606722
2004 Myelin transcription factor 1 (Myt1) modulates the proliferation and differentiation of oligodendrocyte lineage cells. Molecular and cellular neurosciences 89 14962745
1995 Expression of myelin transcription factor I (MyTI), a "zinc-finger" DNA-binding protein, in developing oligodendrocytes. Glia 79 8530187
2008 Myt1 and Ngn3 form a feed-forward expression loop to promote endocrine islet cell differentiation. Developmental biology 74 18394599
2012 The CDK1 inhibitory kinase MYT1 in DNA damage checkpoint recovery. Oncogene 71 23146904
2006 The C. elegans Myt1 ortholog is required for the proper timing of oocyte maturation. Development (Cambridge, England) 70 16421191
2005 The Polo-like kinase Plx1 interacts with and inhibits Myt1 after fertilization of Xenopus eggs. The EMBO journal 66 15692562
2002 A new role for Mos in Xenopus oocyte maturation: targeting Myt1 independently of MAPK. Development (Cambridge, England) 62 11959823
2014 Application of docking and QM/MM-GBSA rescoring to screen for novel Myt1 kinase inhibitors. Journal of chemical information and modeling 60 24490903
2007 Loss of Myt1 function partially compromises endocrine islet cell differentiation and pancreatic physiological function in the mouse. Mechanisms of development 58 17928203
1997 Myt1: a Wee1-type kinase that phosphorylates Cdc2 on residue Thr14. Progress in cell cycle research 57 9552418
2016 Mutations in MYT1, encoding the myelin transcription factor 1, are a rare cause of OAVS. Journal of medical genetics 54 27358179
2016 MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis. Cell reports 54 27705795
2019 Upregulation of Myt1 Promotes Acquired Resistance of Cancer Cells to Wee1 Inhibition. Cancer research 52 31594837
2008 Myt1 protein kinase is essential for Golgi and ER assembly during mitotic exit. The Journal of cell biology 46 18378775
2017 A novel de novo mutation in MYT1, the unique OAVS gene identified so far. European journal of human genetics : EJHG 39 28612832
2006 Identification of both Myt-1 and Wee-1 as necessary mediators of the p21-independent inactivation of the cdc-2/cyclin B1 complex and growth inhibition of TRAMP cancer cells by genistein. The Prostate 39 16924665
2020 ESC-sEVs Rejuvenate Aging Hippocampal NSCs by Transferring SMADs to Regulate the MYT1-Egln3-Sirt1 Axis. Molecular therapy : the journal of the American Society of Gene Therapy 38 33038325
2010 A two-step inactivation mechanism of Myt1 ensures CDK1/cyclin B activation and meiosis I entry. Current biology : CB 38 20362450
2007 Myelin transcription factor 1 (Myt1) expression in demyelinated lesions of rodent and human CNS. Glia 38 17330875
2002 Ectopic expression of the Drosophila Cdk1 inhibitory kinases, Wee1 and Myt1, interferes with the second mitotic wave and disrupts pattern formation during eye development. Genetics 35 12072468
2014 Identification of myelin transcription factor 1 (MyT1) as a subunit of the neural cell type-specific lysine-specific demethylase 1 (LSD1) complex. The Journal of biological chemistry 33 24828497
2002 Dominant mutations in the Caenorhabditis elegans Myt1 ortholog wee-1.3 reveal a novel domain that controls M-phase entry during spermatogenesis. Development (Cambridge, England) 33 12397109
2019 SGK phosphorylates Cdc25 and Myt1 to trigger cyclin B-Cdk1 activation at the meiotic G2/M transition. The Journal of cell biology 32 31537708
2012 MEK1 inactivates Myt1 to regulate Golgi membrane fragmentation and mitotic entry in mammalian cells. The EMBO journal 31 23241949
2011 A critical balance between Cyclin B synthesis and Myt1 activity controls meiosis entry in Xenopus oocytes. Development (Cambridge, England) 30 21795279
2011 A putative transcription factor MYT1 is required for female fertility in the ascomycete Gibberella zeae. PloS one 29 21984921
2004 Keratinocyte G2/M growth arrest by 1,25-dihydroxyvitamin D3 is caused by Cdc2 phosphorylation through Wee1 and Myt1 regulation. The Journal of investigative dermatology 29 15175024
2008 Meiotic inactivation of Xenopus Myt1 by CDK/XRINGO, but not CDK/cyclin, via site-specific phosphorylation. Molecular cell 27 18951089
2019 A Myt1 family transcription factor defines neuronal fate by repressing non-neuronal genes. eLife 26 31386623
2009 c-Jun N-terminal kinase 1 phosphorylates Myt1 to prevent UVA-induced skin cancer. Molecular and cellular biology 26 19204086
2008 Drosophila myt1 is the major cdk1 inhibitory kinase for wing imaginal disc development. Genetics 26 18940789
2014 An RNAi-based suppressor screen identifies interactors of the Myt1 ortholog of Caenorhabditis elegans. G3 (Bethesda, Md.) 25 25298536
2018 Analysis of transcriptional activity by the Myt1 and Myt1l transcription factors. Journal of cellular biochemistry 23 29291346
2005 Drosophila Myt1 is a Cdk1 inhibitory kinase that regulates multiple aspects of cell cycle behavior during gametogenesis. Development (Cambridge, England) 23 16107480
1997 High-grade human brain tumors exhibit increased expression of myelin transcription factor 1 (MYT1), a zinc finger DNA-binding protein. Journal of neuropathology and experimental neurology 22 9210873
2020 MYT1 role in the microtia-craniofacial microsomia spectrum. Molecular genetics & genomic medicine 21 32871052
2016 Myt1 inhibition of Cyclin A/Cdk1 is essential for fusome integrity and premeiotic centriole engagement in Drosophila spermatocytes. Molecular biology of the cell 21 27170181
2008 Mental retardation in a girl with a subtelomeric deletion on chromosome 20q and complete deletion of the myelin transcription factor 1 gene (MYT1). Clinical genetics 21 18341605
2002 NZF-2b is a novel predominant form of mouse NZF-2/MyT1, expressed in differentiated neurons especially at higher levels in newly generated ones. Mechanisms of development 21 12351189
2023 Discovery of Tetrahydropyrazolopyrazine Derivatives as Potent and Selective MYT1 Inhibitors for the Treatment of Cancer. Journal of medicinal chemistry 20 38146659
2018 Myt1 and Myt1l transcription factors limit proliferation in GBM cells by repressing YAP1 expression. Biochimica et biophysica acta. Gene regulatory mechanisms 20 30312684
2002 Identification of Drosophila Myt1 kinase and its role in Golgi during mitosis. Cellular signalling 19 11882391
2017 Viral-mediated overexpression of the Myelin Transcription Factor 1 (MyT1) in the dentate gyrus attenuates anxiety- and ethanol-related behaviors in rats. Psychopharmacology 16 28303373
2024 Myt1 kinase inhibitors - Insight into structural features, offering potential frameworks. Chemico-biological interactions 15 38331334
2013 A fluorescence anisotropy-based Myt1 kinase binding assay. Assay and drug development technologies 15 24229357
2011 JLK1486, a Bis 8-Hydroxyquinoline-Substituted Benzylamine, Displays Cytostatic Effects in Experimental Gliomas through MyT1 and STAT1 Activation and, to a Lesser Extent, PPARγ Activation. Translational oncology 15 21633668
2012 Evaluation of potential Myt1 kinase inhibitors by TR-FRET based binding assay. European journal of medicinal chemistry 14 22770610
2003 Myelin transcription factor 1 (MyT1) immunoreactivity in infants with periventricular leukomalacia. Brain research. Developmental brain research 14 12524179
2023 Myt1 overexpression mediates resistance to cell cycle and DNA damage checkpoint kinase inhibitors. Frontiers in cell and developmental biology 13 38020882
2020 MYT1 attenuates neuroblastoma cell differentiation by interacting with the LSD1/CoREST complex. Oncogene 13 32251364
2009 First total synthesis of 1,2-dipalmitoyl-3-(N-palmitoyl-6'-amino-6'-deoxy-alpha-D-glucosyl)-sn-glycerol--a glycoglycerolipid of a marine alga with a high inhibitor activity against human Myt1-kinase. Carbohydrate research 13 19555926
2012 Synthesis of glycoglycerolipid of 1,2-dipalmitoyl-3-(N-palmitoyl-6'-amino-6'-deoxy-α-D-glucosyl)-sn-glycerol and its analogues, inhibitors of human Myt1-kinase. Carbohydrate research 12 22578528
2025 Myt1 Kinase: An Emerging Cell-Cycle Regulator for Cancer Therapeutics. Clinical cancer research : an official journal of the American Association for Cancer Research 10 39821288
2012 Isolation of a novel Saccharophagus species (Myt-1) capable of degrading a variety of seaweeds and polysaccharides. MicrobiologyOpen 9 22950007
2011 A tool for examining the role of the zinc finger myelin transcription factor 1 (Myt1) in neural development: Myt1 knock-in mice. Transgenic research 9 21267777
2021 Novel MYT1 variants expose the complexity of oculo-auriculo-vertebral spectrum genetic mechanisms. American journal of medical genetics. Part A 8 33880880
2020 Myt1 Kinase Couples Mitotic Cell Cycle Exit with Differentiation in Drosophila. Cell reports 7 33207203
2018 PICOT binding to the polycomb group protein, EED, alters H3K27 methylation at the MYT1 PRC2 target gene. Biochemical and biophysical research communications 7 30595380
2013 Purification and characterization of an alkaliphilic alginate lyase AlgMytC from Saccharophagus sp. Myt-1. Journal of microbiology and biotechnology 7 23676907
2015 Identification of peptidic substrates for the human kinase Myt1 using peptide microarrays. Bioorganic & medicinal chemistry 5 26059593
2006 Autophosphorylation of Ser66 on Xenopus Myt1 is a prerequisite for meiotic inactivation of Myt1. Cell cycle (Georgetown, Tex.) 5 16481744
2021 Dysregulation of Myt1 expression acts as a potential peripheral biomarker for major depressive disorder and bipolar disorder. Journal of neurogenetics 4 34011236
2014 The glycoglycerolipid 1,2-dipalmitoyl-3-(N-palmitoyl-6'-amino-6'-deoxy-α-d-glucosyl)-sn-glycerol is no inhibitor of the human Myt1 kinase. Journal of enzyme inhibition and medicinal chemistry 4 24939100
2013 Cloning and Characterizing the Thermophilic and Detergent Stable Cellulase CelMytB from Saccharophagus sp. Myt-1. Indian journal of microbiology 4 24426162
2024 Nzf2 promotes oligodendrocyte differentiation and regeneration via repressing HDAC1-mediated histone deacetylation. Science advances 3 39671488
2025 Diabetes-associated MYT1 and MYT3 regulate human β-cell insulin secretion and survival via other diabetes-risk genes. bioRxiv : the preprint server for biology 2 40060649
2024 Myelin Transcription Factor 1 (MyT1) overexpression mitigates social isolation-induced behavioral deficits: Insights into cortical synaptotagmin 1 regulation and antidepressant-like effects. Pharmacology, biochemistry, and behavior 2 39592028
2021 Regulation of Myt1 kinase activity via its N-terminal region in Xenopus meiosis and mitosis. Cells & development 2 34695617
2019 Involvement of Myt1 kinase in the G2 phase of the first cell cycle in Xenopus laevis. Biochemical and biophysical research communications 2 31128913
2026 Diabetes-associated MYT1 and ST18 genes regulate human beta cell insulin secretion and survival via other diabetes risk genes. Diabetologia 0 42247169

Missed literature

Know a paper Affinage missed for MYT1? Flag it for the maintainers and the community.

No submissions yet.