Affinage

PEA15

Astrocytic phosphoprotein PEA-15 · UniProt Q15121

Length
130 aa
Mass
15.0 kDa
Annotated
2026-04-29
100 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PEA15 is a death effector domain (DED)-containing scaffold protein that governs the balance between cell proliferation, apoptosis, and autophagy by directing the subcellular localization and activity of ERK1/2 MAP kinases and the apoptotic adaptor FADD. PEA15 sequesters activated ERK1/2 in the cytoplasm by occupying the MAP kinase insert and both the DEF and D docking sites of ERK2, thereby blocking nucleoporin-mediated nuclear import and protecting ERK2 from dephosphorylation while inhibiting its catalytic activity (PMID:11702783, PMID:14707138, PMID:23575685). Phosphorylation at Ser-104 by PKC releases ERK binding, whereas phosphorylation at Ser-116 by CaMKII, AKT, or AMPK switches PEA15 toward FADD binding and anti-apoptotic function; these modifications are reversed by PP4 and DUSP7 (PMID:15916534, PMID:25096718, PMID:27317964, PMID:34907034). PEA15 also scaffolds ERK–RSK2 complexes to enhance RSK2 activation and CREB-dependent transcription, interacts with PLD1 to modulate PKC-α activity and insulin-stimulated glucose uptake, and is itself targeted for chaperone-mediated autophagy via HSC70 recognition of KFERQ motifs in a phosphorylation-regulated manner (PMID:18077417, PMID:18541525, PMID:24477641).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 High

    The DED of PEA15 was identified as required for blocking Ras-mediated integrin suppression via R-Ras, establishing PEA15 as a DED-containing signaling adaptor acting downstream of Ras.

    Evidence Expression cloning screen with DED mutagenesis and dominant-negative R-Ras epistasis in integrin activation assays

    PMID:9852038

    Open questions at the time
    • R-Ras binding mechanism not defined at molecular level
    • direct vs. indirect effect on integrin not resolved
  2. 2001 High

    Establishing the core mechanism: PEA15 was shown to sequester ERK1/2 in the cytoplasm via a nuclear export sequence, preventing ERK-dependent transcription and proliferation—answering how a small DED protein could control MAPK output.

    Evidence PEA15 genetic knockout with ERK localization assays, NES mutagenesis, and transcription reporters

    PMID:11702783

    Open questions at the time
    • Exact binding interface on ERK2 unknown at this point
    • mechanism of nuclear pore exclusion not resolved
  3. 2004 High

    The molecular basis of cytoplasmic ERK retention was resolved: PEA15 occupies the MAP kinase insert of ERK2, directly competing with nucleoporin binding required for nuclear import.

    Evidence Permeabilized cell nuclear import assay with ERK2 MAP kinase insert mutants and nucleoporin co-IP

    PMID:14707138

    Open questions at the time
    • Structural details of the PEA15–ERK2 interface not yet available
    • role of other docking sites unresolved
  4. 2005 High

    The phosphorylation switch controlling PEA15 partner selection was defined: Ser-104 phosphorylation (PKC) releases ERK binding, while Ser-116 phosphorylation (CaMKII/AKT) promotes FADD binding, answering how one protein toggles between proliferation and apoptosis control.

    Evidence Phospho-site mutagenesis with in vitro and in vivo binding assays and phospho-epitope antibodies

    PMID:15916534

    Open questions at the time
    • Structural basis of phosphorylation-induced conformational change unknown
    • whether both sites must be phosphorylated simultaneously for full FADD switch unclear
  5. 2005 Medium

    A C-terminal reverse DEJL-like motif in PEA15 was identified as competing with ERK substrates for D-site docking, providing a molecular explanation for substrate-level inhibition beyond cytoplasmic sequestration.

    Evidence Fluorescence anisotropy binding assays and peptide competition experiments

    PMID:16324895

    Open questions at the time
    • DEJL motif mutagenesis not validated in cells
    • contribution relative to MAP kinase insert binding not quantified
  6. 2003 High

    PEA15 was found to directly bind and inhibit RSK2 (not RSK1) via its C-terminal tail, establishing a second MAPK pathway target and showing PEA15 sequesters RSK2 in the cytoplasm after EGF stimulation.

    Evidence Co-IP, in vitro binding with purified proteins, subcellular fractionation, RSK2 kinase assay, CREB transcription reporter

    PMID:12796492

    Open questions at the time
    • Structural basis of RSK2 selectivity over RSK1 unknown
    • whether ERK and RSK2 bind PEA15 simultaneously not tested
  7. 2007 High

    PEA15 was re-evaluated as a positive scaffold: it simultaneously binds ERK and RSK2, enhancing RSK2 activation and CREB transcription—resolving the apparent paradox of PEA15 acting as both an ERK inhibitor and an ERK pathway facilitator.

    Evidence Reciprocal co-IPs, in vitro binding, kinase assays, CREB reporter, and rescue of PEA15-null lymphocytes

    PMID:18077417

    Open questions at the time
    • Stoichiometry of the ternary ERK–PEA15–RSK2 complex not determined
    • phosphorylation-state dependence partially characterized
  8. 2008 High

    PEA15 was linked to metabolic regulation through direct binding to PLD1 via its N-terminal residues 1–24, increasing PKC-α activity and impairing insulin-stimulated glucose uptake—explaining PEA15's role in insulin resistance.

    Evidence SPR binding (KD measured), competing PED-1-24 peptide in cells and transgenic mouse myocytes, glucose uptake assay

    PMID:18541525

    Open questions at the time
    • Structural details of PEA15–PLD1 interface unresolved
    • physiological relevance beyond overexpression model not fully established
  9. 2013 High

    Crystal structures of PEA15 bound to three ERK2 phospho-conformers revealed a bipartite binding mode occupying both DEF and D docking sites, with allosteric disruption of active ERK2 features—providing the atomic-level explanation for how PEA15 simultaneously inhibits ERK2 catalysis and protects it from dephosphorylation.

    Evidence X-ray crystallography of PEA15–ERK2 complexes in three phosphorylation states

    PMID:23575685

    Open questions at the time
    • Solution dynamics of the complex not characterized
    • how phosphorylation at Ser-104 disrupts this interface not structurally resolved
  10. 2014 High

    AMPK was identified as a third kinase phosphorylating PEA15 at Ser-116, linking metabolic stress sensing to PEA15-mediated anoikis resistance and establishing PEA15 as an integration node for energy and survival signaling.

    Evidence In vitro kinase assay, S116A mutagenesis, AMPK knockdown/inhibition, mammosphere formation, xenograft assay

    PMID:25096718

    Open questions at the time
    • Whether AMPK-mediated phosphorylation shifts PEA15 toward FADD or away from ERK not directly tested
    • relative contribution of AMPK vs. AKT/CaMKII in vivo unclear
  11. 2014 Medium

    HSC70-mediated chaperone-mediated autophagy (CMA) was identified as the degradation pathway for PEA15, with phosphorylation at Ser-104/116 masking a KFERQ motif to stabilize PEA15—providing a mechanism for phosphorylation-dependent control of PEA15 protein levels.

    Evidence TAP-MS identification of HSC70 interaction, CMA lysosomal degradation assay, phosphomimetic/nonphosphorylatable mutants

    PMID:24477641

    Open questions at the time
    • CMA targeting not confirmed in an independent lab
    • relative contribution of CMA vs. proteasomal degradation unclear
    • KFERQ motif mutagenesis not performed
  12. 2010 Medium

    PEA15 was shown to activate JNK signaling in a phosphorylation-dependent manner, promoting autophagy in glioma cells—expanding PEA15's signaling repertoire beyond ERK/FADD to include stress kinase-driven autophagy.

    Evidence PEA15 overexpression and siRNA with JNK activity assays, non-phosphorylatable mutants, autophagy markers

    PMID:20452983

    Open questions at the time
    • Direct PEA15–JNK interaction not demonstrated
    • mechanism of JNK activation by PEA15 not defined
    • single lab observation
  13. 2012 Medium

    Hexokinase II was identified as a PEA15 binding partner that cooperates with PEA15 to inhibit apoptosis under hypoxia but promotes apoptosis under glucose deprivation when PEA15 is absent, revealing a metabolic context-dependent apoptotic switch.

    Evidence Co-immunoprecipitation, PEA15 knockdown, apoptosis assays under hypoxia and glucose deprivation

    PMID:22233811

    Open questions at the time
    • Direct binding interface not mapped
    • no structural or in vitro reconstitution
    • mechanistic link between HKII metabolic function and PEA15 anti-apoptotic activity unclear
  14. 2016 Medium

    PP4 was established as a phosphatase that dephosphorylates PEA15 and whose growth-inhibitory effects depend on PEA15, placing PEA15 dephosphorylation as a functionally relevant regulatory event.

    Evidence PP4c overexpression/siRNA with PEA15 siRNA rescue, phospho-PEA15 immunoblotting, apoptosis and proliferation assays

    PMID:27317964

    Open questions at the time
    • Direct enzyme–substrate relationship not confirmed by in vitro phosphatase assay
    • specific Ser site targeted by PP4 not determined
  15. 2022 Medium

    DUSP7 was identified as a second phosphatase for PEA15, transcriptionally driven by FOSL1, linking AP-1 family transcription factor signaling to PEA15 dephosphorylation and drug resistance.

    Evidence ChIP-seq/luciferase reporter for FOSL1→DUSP7, phospho-PEA15 immunoblotting, siRNA knockdown, doxorubicin resistance assays in vitro and in vivo

    PMID:34907034

    Open questions at the time
    • Direct DUSP7–PEA15 enzyme–substrate interaction not reconstituted in vitro
    • site specificity of DUSP7 on PEA15 not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How Ser-104 phosphorylation structurally disrupts the PEA15–ERK2 interface, the stoichiometry and dynamics of the ternary PEA15–ERK–RSK2 complex, and the relative contributions of CMA versus proteasomal turnover to PEA15 protein levels remain unresolved.
  • No structure of phospho-Ser104 PEA15 bound or released from ERK2
  • ternary PEA15–ERK–RSK2 complex not structurally characterized
  • in vivo quantification of PEA15 degradation routes not performed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0098772 molecular function regulator activity 4
Localization
GO:0005829 cytosol 4
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-5357801 Programmed Cell Death 5 R-HSA-9612973 Autophagy 3
Partners
FADDHKIIHSC70HSPB1MAPK1MAPK3PLD1RPS6KA3

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 PEA-15 binds ERK1/2 MAP kinases and sequesters them in the cytoplasm by preventing their nuclear localization, thereby blocking ERK-dependent transcription and cell proliferation. PEA-15 contains a nuclear export sequence required for this cytoplasmic anchoring function. Genetic deletion of PEA-15 with ERK localization assays, nuclear export sequence mutagenesis, transcription reporter assays Developmental cell High 11702783
2004 PEA-15 prevents ERK2 nuclear entry by occupying the MAP kinase insert of ERK2 (required for MEK1 and nucleoporin binding), thereby blocking ERK2 interaction with nucleoporins of the nuclear pore complex. Permeabilized cell nuclear import assay, binding assays with ERK2 MAP kinase insert mutants, co-IP with nucleoporins The Journal of biological chemistry High 14707138
2013 Crystal structures of PEA-15 bound to three different ERK2 phospho-conformers reveal that PEA-15 uses a bipartite binding mode occupying two key docking sites of ERK2 (the DEF/F-site and D-site), triggers an allosteric conduit in dually phosphorylated ERK2 disrupting active ERK2 features, and protects ERK2 from dephosphorylation while inhibiting its activity. X-ray crystallography of PEA-15–ERK2 complexes in three phosphorylation states Nature communications High 23575685
2005 Phosphorylation of PEA-15 at Ser-104 (by PKC) blocks ERK binding in vitro and in vivo, whereas phosphorylation at Ser-116 (by CamKII or AKT) promotes PEA-15 binding to the pro-apoptotic adaptor FADD. Thus phosphorylation acts as a molecular switch controlling whether PEA-15 regulates proliferation (via ERK) or apoptosis (via FADD). Phospho-specific mutagenesis, in vitro binding assays, co-immunoprecipitation from cells, phospho-epitope antibody characterization The Biochemical journal High 15916534
1998 The death effector domain (DED) of PEA-15 is essential for blocking Ras-mediated suppression of integrin activation, acting via a pathway dependent on the small GTPase R-Ras, without affecting ERK MAP kinase activation by Ras. Expression cloning screen, DED mutagenesis, dominant-negative R-Ras epistasis, integrin activation assays The Journal of biological chemistry High 9852038
2003 PEA-15 directly binds RSK2 (but not RSK1) via its C-terminal tail (not the DED), sequesters RSK2 in the cytoplasm after EGF stimulation, and inhibits RSK2 kinase activity by ~50%, thereby blocking RSK2-dependent CREB transcription and histone H3 phosphorylation. Co-immunoprecipitation from cells, in vitro binding with purified proteins, subcellular fractionation, kinase activity assay, transcription reporter assay The Journal of biological chemistry High 12796492
2007 PEA-15 acts as a scaffold that simultaneously binds ERK and RSK2, increases ERK-RSK2 association in a concentration-dependent manner, and thereby enhances RSK2 activation and CREB-mediated transcription. This scaffolding activity is regulated by phosphorylation of PEA-15. Co-immunoprecipitation, in vitro binding assays, kinase assays, CREB transcription reporter, PEA-15-null lymphocyte rescue experiment Proceedings of the National Academy of Sciences of the United States of America High 18077417
2008 PEA-15 (PED) directly interacts with the C-terminal D4 domain of phospholipase D1 (PLD1) via its N-terminal residues 1–24, and this interaction increases PKC-alpha activity; disrupting PEA-15–PLD1 binding restores insulin-stimulated glucose uptake in skeletal muscle cells overexpressing PED. Surface plasmon resonance, ELISA-like binding assay, co-immunoprecipitation, competing peptide (PED-1-24) in cell models and transgenic mouse myocytes, glucose uptake assay The Journal of biological chemistry High 18541525
2012 Hexokinase II (HKII) directly interacts with PEA-15 to form a molecular switch governing cell fate: together they inhibit apoptosis after hypoxia, whereas HKII alone accelerates apoptosis under glucose deprivation/absence of PEA-15. Co-immunoprecipitation, loss-of-function (PEA-15 KD), apoptosis assays under hypoxia and glucose deprivation conditions Proceedings of the National Academy of Sciences of the United States of America Medium 22233811
2014 AMPK directly phosphorylates PEA-15 at Ser-116, and this phosphorylation promotes PEA-15 anti-apoptotic function and anoikis resistance in mammary epithelial cells. AMPK and PEA-15 co-immunoprecipitate and AMPK phosphorylates PEA-15 in vitro. Immunoprecipitation, in vitro kinase assay, non-phosphorylatable S116A mutant expression, AMPK inhibition/knockdown, mammosphere formation, xenograft assay Breast cancer research : BCR High 25096718
2014 HSC70 interacts with PEA-15 at KFERQ-like motifs and targets it for chaperone-mediated autophagy (CMA); phosphorylation of PEA-15 at Ser-104/116 blocks HSC70 access to one KFERQ motif, preventing lysosomal degradation and shifting PEA-15 function from tumor suppression to tumor promotion. Tandem affinity purification (TAP-MS), co-immunoprecipitation, CMA lysosomal degradation assay, phosphomimetic/nonphosphorylatable mutants Journal of cellular physiology Medium 24477641
2010 PEA-15 overexpression activates JNK signaling in a phosphorylation-dependent manner (requiring both Ser-104 and Ser-116), and JNK activation by PEA-15 promotes autophagy in glioma cells in response to irradiation, serum deprivation, or rapamycin. PEA-15 overexpression, JNK activity assay, siRNA knockdown of PEA-15, non-phosphorylatable mutants, autophagy markers The Journal of biological chemistry Medium 20452983
2008 PTEN regulates Fas (type I vs. type II) apoptosis pathway selection, at least in part, by controlling PEA-15 phosphorylation and activity, which in turn regulates Bcl-2-sensitive mitochondrial apoptosis. PTEN loss/gain-of-function in cell lines, Pten haploinsufficient mice, Bcl-2 transgenic animals, Fas apoptosis pathway analysis Molecular and cellular biology Medium 19103758
2012 TGF-beta1 transcriptionally upregulates PEA-15 expression in skeletal muscle cells via a PP2A/FoxO1-mediated mechanism; PEA-15 in turn induces autophagy and blocks myoblast differentiation into myotubes. In vivo, PEA-15 transgenic mice show atrophic muscle fibers with increased LC3II/I ratio. PEA-15 shRNA, stable overexpression, TGF-beta1 treatment, LC3 ratio measurement, differentiation assays, transgenic mouse histology Cell death and differentiation Medium 22281705
2011 Hsp27 regulates PEA-15 activity in an Akt-dependent manner: Hsp27 silencing promotes PEA-15–ERK binding (cytoplasmic ERK sequestration, reducing proliferation) while simultaneously releasing FADD from PEA-15 (allowing death receptor apoptosis signaling). Hsp27 siRNA, Akt inhibition, co-immunoprecipitation of PEA-15 with ERK and FADD, proliferation and Fas apoptosis assays Cell death and differentiation Medium 22179576
2016 Protein phosphatase 4 (PP4c) dephosphorylates PEA-15 and regulates breast cancer cell survival; PP4c-mediated growth inhibition and pro-apoptotic effects are lost upon PEA-15 knockdown, placing PP4c upstream of PEA-15 in a survival signaling axis. PP4c overexpression/siRNA, PEA-15 siRNA rescue experiment, immunoblotting for phospho-PEA-15, apoptosis and proliferation assays Cellular signalling Medium 27317964
2022 FOSL1 transcriptionally upregulates DUSP7 (dual specificity phosphatase 7), which dephosphorylates PEA-15 and thereby promotes drug resistance in breast cancer cells. ChIP-seq/luciferase reporter for FOSL1→DUSP7 transcription, immunoblotting for phospho-PEA-15, siRNA knockdown, in vitro and in vivo doxorubicin resistance assays Molecular cancer research : MCR Medium 34907034
2005 PEA-15 inhibits ERK2 by blocking DEJL-domain-containing substrates from binding ERK2, acting via a C-terminal reverse DEJL-like motif (residues 121-LXLXXXXKK-129) that competes with ERK-binding substrates. Quantitative fluorescence anisotropy measurements determined binding affinity. Fluorescence anisotropy binding assays, peptide competition experiments, equilibrium binding modeling Biochimica et biophysica acta Medium 16324895
2015 Latent HCMV infection of myeloid CD34+ progenitor cells upregulates PEA-15 downstream of cellular IL-10 signaling, and this PEA-15 upregulation mediates protection from FAS-mediated apoptosis. HCMV latent infection model, IL-10 signaling perturbation, PEA-15 expression analysis, FAS apoptosis assays in primary CD34+ cells The Journal of general virology Medium 25957098
2011 In H-Ras-transformed epithelial cells, PEA-15 promotes transformation by activating its binding partner PLD1; PEA-15/PLD1 interaction increases PLD1 expression and activity, leading to enhanced ERK activation, accelerated G1/S cell cycle entry, and increased tumor growth in vivo. PLD1 inhibition, interference with PEA-15/PLD1 binding, soft agar colony growth, xenograft tumor assay, ERK phosphorylation assays Oncogene Medium 22105357

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 PEA-15 mediates cytoplasmic sequestration of ERK MAP kinase. Developmental cell 270 11702783
1995 MAT1 ('menage à trois') a new RING finger protein subunit stabilizing cyclin H-cdk7 complexes in starfish and Xenopus CAK. The EMBO journal 212 7588631
1995 In vitro assembly of a functional human CDK7-cyclin H complex requires MAT1, a novel 36 kDa RING finger protein. The EMBO journal 181 8521818
1997 Regulation of CDK7 substrate specificity by MAT1 and TFIIH. The EMBO journal 162 9130709
2001 T-loop phosphorylation stabilizes the CDK7-cyclin H-MAT1 complex in vivo and regulates its CTD kinase activity. The EMBO journal 117 11447116
1996 MAT1, cdk7 and cyclin H form a kinase complex which is UV light-sensitive upon association with TFIIH. The EMBO journal 114 8617234
2010 miR-212 increases tumor necrosis factor-related apoptosis-inducing ligand sensitivity in non-small cell lung cancer by targeting the antiapoptotic protein PED. Cancer research 111 20388802
2014 Mitochondrial oxidative phosphorylation TRAP(1)ped in tumor cells. Trends in cell biology 110 24731398
2021 PED in 2021: a major update of the protein ensemble database for intrinsically disordered proteins. Nucleic acids research 103 33305318
2009 Precision extruding deposition (PED) fabrication of polycaprolactone (PCL) scaffolds for bone tissue engineering. Biofabrication 100 20811098
2001 A DNA replication-arrest site RTS1 regulates imprinting by determining the direction of replication at mat1 in S. pombe. Genes & development 100 11511538
1991 A novel switch-activating site (SAS1) and its cognate binding factor (SAP1) required for efficient mat1 switching in Schizosaccharomyces pombe. The EMBO journal 95 1915277
1987 Analysis of Qa-2 antigen expression by preimplantation mouse embryos: possible relationship to the preimplantation-embryo-development (Ped) gene product. Biology of reproduction 95 3593833
2005 Phosphorylation of PEA-15 switches its binding specificity from ERK/MAPK to FADD. The Biochemical journal 94 15916534
2010 Functional characterization of MAT1-1-specific mating-type genes in the homothallic ascomycete Sordaria macrospora provides new insights into essential and nonessential sexual regulators. Eukaryotic cell 91 20435701
1998 The death effector domain of PEA-15 is involved in its regulation of integrin activation. The Journal of biological chemistry 81 9852038
2001 Inability to enter S phase and defective RNA polymerase II CTD phosphorylation in mice lacking Mat1. The EMBO journal 79 11387217
2003 Evidence that HLA-G is the functional homolog of mouse Qa-2, the Ped gene product. Human immunology 74 14602227
2013 Structure of ERK2 bound to PEA-15 reveals a mechanism for rapid release of activated MAPK. Nature communications 71 23575685
1995 Two-step activation of meiosis by the mat1 locus in Schizosaccharomyces pombe. Molecular and cellular biology 71 7651414
2004 The death effector domain protein PEA-15 prevents nuclear entry of ERK2 by inhibiting required interactions. The Journal of biological chemistry 70 14707138
2000 Distinct regions of MAT1 regulate cdk7 kinase and TFIIH transcription activities. The Journal of biological chemistry 70 10801852
2009 Frontiers: PED/PEA-15, a multifunctional protein controlling cell survival and glucose metabolism. American journal of physiology. Endocrinology and metabolism 69 19531639
2003 The multifunctional protein PEA-15 is involved in the control of apoptosis and cell cycle in astrocytes. Biochemical pharmacology 66 14555237
2012 Mitochondrial hexokinase II (HKII) and phosphoprotein enriched in astrocytes (PEA15) form a molecular switch governing cellular fate depending on the metabolic state. Proceedings of the National Academy of Sciences of the United States of America 61 22233811
2006 The wild-type Schizosaccharomyces pombe mat1 imprint consists of two ribonucleotides. EMBO reports 61 16299470
1996 The major astrocytic phosphoprotein PEA-15 is encoded by two mRNAs conserved on their full length in mouse and human. The Journal of biological chemistry 61 8662970
2014 Identification of a novel AMPK-PEA15 axis in the anoikis-resistant growth of mammary cells. Breast cancer research : BCR 56 25096718
2014 Phosphorylation-regulated degradation of the tumor-suppressor form of PED by chaperone-mediated autophagy in lung cancer cells. Journal of cellular physiology 54 24477641
2003 RSK2 activity is regulated by its interaction with PEA-15. The Journal of biological chemistry 54 12796492
1997 The cdk7-cyclin H-MAT1 complex associated with TFIIH is localized in coiled bodies. Molecular biology of the cell 54 9243502
1995 Molecular cloning of CDK7-associated human MAT1, a cyclin-dependent kinase-activating kinase (CAK) assembly factor. Cancer research 51 8521393
2007 ERK MAP kinase is targeted to RSK2 by the phosphoprotein PEA-15. Proceedings of the National Academy of Sciences of the United States of America 46 18077417
1992 Removal of Qa-2 antigen alters the Ped gene phenotype of preimplantation mouse embryos. Biology of reproduction 45 1327207
2000 Solution structure of the N-terminal domain of the human TFIIH MAT1 subunit: new insights into the RING finger family. The Journal of biological chemistry 42 11056162
1997 Cell differentiation by interaction of two HMG-box proteins: Mat1-Mc activates M cell-specific genes in S.pombe by recruiting the ubiquitous transcription factor Ste11 to weak binding sites. The EMBO journal 42 9233811
2019 Current Status of Porcine Epidemic Diarrhoea (PED) in European Pigs. Journal of veterinary research 41 31934654
2011 Hsp27 silencing coordinately inhibits proliferation and promotes Fas-induced apoptosis by regulating the PEA-15 molecular switch. Cell death and differentiation 40 22179576
1998 Role of the Ped gene and apoptosis genes in control of preimplantation development. Journal of assisted reproduction and genetics 40 9604770
2020 Structural basis for CDK7 activation by MAT1 and Cyclin H. Proceedings of the National Academy of Sciences of the United States of America 38 33055219
2014 Phosphoprotein enriched in astrocytes (PEA)-15: a potential therapeutic target in multiple disease states. Pharmacology & therapeutics 38 24657708
2008 Mating type protein Mat1-2 from asexual Aspergillus fumigatus drives sexual reproduction in fertile Aspergillus nidulans. Eukaryotic cell 38 18245277
2012 Phosphorylation is the switch that turns PEA-15 from tumor suppressor to tumor promoter. Small GTPases 37 22694972
2008 PED is overexpressed and mediates TRAIL resistance in human non-small cell lung cancer. Journal of cellular and molecular medicine 36 18284607
2010 PEA-15 inhibits tumorigenesis in an MDA-MB-468 triple-negative breast cancer xenograft model through increased cytoplasmic localization of activated extracellular signal-regulated kinase. Clinical cancer research : an official journal of the American Association for Cancer Research 35 20215547
2010 Melatonin ameliorates ischemic-like injury-evoked nitrosative stress: Involvement of HtrA2/PED pathways in endothelial cells. Journal of pineal research 35 21198825
2008 PTEN loss promotes mitochondrially dependent type II Fas-induced apoptosis via PEA-15. Molecular and cellular biology 35 19103758
2006 The PEA15 gene is overexpressed and related to insulin resistance in healthy first-degree relatives of patients with type 2 diabetes. Diabetologia 35 17021921
2013 Isolation of the MAT1-1 mating type idiomorph and evidence for selfing in the Chinese medicinal fungus Ophiocordyceps sinensis. Fungal biology 34 24012300
2012 PED/PEA-15 induces autophagy and mediates TGF-beta1 effect on muscle cell differentiation. Cell death and differentiation 34 22281705
2008 Targeting of PED/PEA-15 molecular interaction with phospholipase D1 enhances insulin sensitivity in skeletal muscle cells. The Journal of biological chemistry 34 18541525
2008 Epigalocatechin-3-gallate (EGCG) downregulates PEA15 and thereby augments TRAIL-mediated apoptosis in malignant glioma. Neuroscience letters 34 18948169
2009 Proteomic differential display analysis identified upregulated astrocytic phosphoprotein PEA-15 in human malignant pleural mesothelioma cell lines. Proteomics 32 19771552
2006 Antitumor effect of E1A in ovarian cancer by cytoplasmic sequestration of activated ERK by PEA15. Oncogene 32 16170361
2005 Phylogenetic relationships between members of the crucifer pathogenic Leptosphaeria maculans species complex as shown by mating type (MAT1-2), actin, and beta-tubulin sequences. Molecular phylogenetics and evolution 32 16122948
1991 The mechanism of fission yeast mating type interconversion: seal/replicate/cleave model of replication across the double-stranded break site at mat1. Genetics 32 2016051
2002 The cyclin H/cdk7/Mat1 kinase activity is regulated by CK2 phosphorylation of cyclin H. Oncogene 30 12140753
2001 MAT1-modulated CAK activity regulates cell cycle G(1) exit. Molecular and cellular biology 30 11113200
2008 Mat1 inhibits peroxisome proliferator-activated receptor gamma-mediated adipocyte differentiation. Molecular and cellular biology 29 18981214
1997 Is Cdk7/cyclin H/MAT1 the genuine cdk activating kinase in cycling Xenopus egg extracts? Oncogene 29 9315098
1994 Identification of a mammary transforming gene (MAT1) associated with mouse mammary carcinogenesis. Proceedings of the National Academy of Sciences of the United States of America 29 7937892
2015 Latent infection of myeloid progenitors by human cytomegalovirus protects cells from FAS-mediated apoptosis through the cellular IL-10/PEA-15 pathway. The Journal of general virology 28 25957098
2014 Quantitative proteomics reveals that PEA15 regulates astroglial Aβ phagocytosis in an Alzheimer's disease mouse model. Journal of proteomics 28 25108202
2000 Fate of mat1 DNA strands during mating-type switching in fission yeast. EMBO reports 28 11265754
2016 Parkinson-like phenotype in insulin-resistant PED/PEA-15 transgenic mice. Scientific reports 27 27426254
2011 PEA-15 potentiates H-Ras-mediated epithelial cell transformation through phospholipase D. Oncogene 27 22105357
1981 The mat-1 gene in Chlamydomonas regulates DNA methylation during gametogenesis. Cell 27 6263491
2010 The PEA-15 protein regulates autophagy via activation of JNK. The Journal of biological chemistry 26 20452983
1999 Search for a human homologue of the mouse Ped gene. Molecular human reproduction 26 10341001
2010 Functional analysis of the Cdk7.cyclin H.Mat1 complex in mouse embryonic stem cells and embryos. The Journal of biological chemistry 25 20231280
1999 Identification of two major histocompatibility complex class Ib genes, Q7 and Q9, as the Ped gene in the mouse. Biology of reproduction 25 10208972
2017 Phosphoprotein enriched in diabetes (PED/PEA15) promotes migration in hepatocellular carcinoma and confers resistance to sorafenib. Cell death & disease 24 29072691
2011 MEK1/2 inhibitor selumetinib (AZD6244) inhibits growth of ovarian clear cell carcinoma in a PEA-15-dependent manner in a mouse xenograft model. Molecular cancer therapeutics 24 22144664
2010 The time course of unconditioned morphine-induced psychomotor sensitization mirrors the phosphorylation of FADD and MEK/ERK in rat striatum: role of PEA-15 as a FADD-ERK binding partner in striatal plasticity. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 24 19758790
2005 Quantifying ERK2-protein interactions by fluorescence anisotropy: PEA-15 inhibits ERK2 by blocking the binding of DEJL domains. Biochimica et biophysica acta 24 16324895
2004 Biochemical interactions between proteins and mat1 cis-acting sequences required for imprinting in fission yeast. Molecular and cellular biology 24 15509785
2018 PEA15 promotes liver metastasis of colorectal cancer by upregulating the ERK/MAPK signaling pathway. Oncology reports 23 30365128
2006 Tagging target genes of the MAT1-2-1 transcription factor in Fusarium verticillioides (Gibberella fujikuroi MP-A). Antonie van Leeuwenhoek 23 17124547
1998 Differential expression of Ped gene candidates in preimplantation mouse embryos. Biology of reproduction 23 9746747
2022 Transcription Factor FOSL1 Enhances Drug Resistance of Breast Cancer through DUSP7-Mediated Dephosphorylation of PEA15. Molecular cancer research : MCR 22 34907034
2003 PEA-15 modulates TNFalpha intracellular signaling in astrocytes. Annals of the New York Academy of Sciences 22 15033692
2002 Conditional ablation of the Mat1 subunit of TFIIH in Schwann cells provides evidence that Mat1 is not required for general transcription. Journal of cell science 22 12376559
2020 ZNF703 promotes tumor progression in ovarian cancer by interacting with HE4 and epigenetically regulating PEA15. Journal of experimental & clinical cancer research : CR 21 33246486
2000 Molecular characterization of the human PEA15 gene on 1q21-q22 and association with type 2 diabetes mellitus in Pima Indians. Gene 21 10607908
1999 RNA antisense abrogation of MAT1 induces G1 phase arrest and triggers apoptosis in aortic smooth muscle cells. The Journal of biological chemistry 21 10026172
2012 Ferulic acid prevents the cerebral ischemic injury-induced decreases of astrocytic phosphoprotein PEA-15 and its two phosphorylated forms. Neuroscience letters 20 22306184
2000 Expression of MAT1/PEA-15 mRNA isoforms during physiological and neoplastic changes in the mouse mammary gland. Cancer letters 20 10737714
2018 PED subunit vaccine based on COE domain replacement of flagellin domain D3 improved specific humoral and mucosal immunity in mice. Vaccine 19 29426660
2011 Cloning and analysis of the MAT1-2-1 gene from the traditional Chinese medicinal fungus Ophiocordyceps sinensis. Fungal biology 19 21802050
2017 The novel Aspergillus fumigatus MAT1-2-4 mating-type gene is required for mating and cleistothecia formation. Fungal genetics and biology : FG & B 18 28889020
2015 Biomechanical insult switches PEA-15 activity to uncouple its anti-apoptotic function and promote erk mediated tissue remodeling. Experimental cell research 18 26615958
2014 PEP-1-PEA-15 protects against toxin-induced neuronal damage in a mouse model of Parkinson's disease. Biochimica et biophysica acta 18 24412329
2005 Rapid Ped-2E9 cell-based cytotoxicity analysis and genotyping of Bacillus species. Journal of clinical microbiology 18 16333068
2010 Hepatocyte nuclear factor (HNF)-4alpha-driven epigenetic silencing of the human PED gene. Diabetologia 17 20396999
2024 Enhancing humoral and mucosal immune response of PED vaccine candidate by fusing S1 protein to nanoparticle multimerization. Veterinary microbiology 16 38262114
2020 Mitochondrial PCK2 Missense Variant in Shetland Sheepdogs with Paroxysmal Exercise-Induced Dyskinesia (PED). Genes 16 32660061
2016 Direct repeat-mediated DNA deletion of the mating type MAT1-2 genes results in unidirectional mating type switching in Sclerotinia trifoliorum. Scientific reports 16 27255676
2011 The MAT1-2-1 mating-type gene upregulates photo-inducible carotenoid biosynthesis in Fusarium verticillioides. FEMS microbiology letters 16 21314709
2019 MAT1 facilitates the lung metastasis of osteosarcoma through upregulation of AKT1 expression. Life sciences 15 31421084
2016 The protein phosphatase 4 - PEA15 axis regulates the survival of breast cancer cells. Cellular signalling 15 27317964