Affinage

PCGF2

Polycomb group RING finger protein 2 · UniProt P35227

Length
344 aa
Mass
37.8 kDa
Annotated
2026-04-29
52 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PCGF2 (MEL-18) is a Polycomb group RING-finger protein that functions as a core subunit of canonical PRC1 (cPRC1.2), directing Ring1B E3 ubiquitin ligase activity to monoubiquitylate histone H2A at lysine 119 in a phosphorylation-dependent manner, and organizing three-dimensional chromatin architecture at bivalent promoters to maintain genes in a poised but silent state (PMID:17936708, PMID:8521824). Beyond its canonical PRC1 role, PCGF2 inhibits global sumoylation by directly binding and sequestering the SUMO E2 enzyme UBC9, thereby regulating the sumoylation status of substrates including HSF2, RanGAP1, and PML-RARA, with this inhibitory interaction modulated during the cell cycle and by arsenic trioxide treatment (PMID:18211895, PMID:27030546). PCGF2 controls cell proliferation, stem cell self-renewal, and lineage commitment across hematopoietic, immune, and neural systems by repressing Hox genes, Bmi-1, and c-Myc and by modulating PI3K/Akt signaling downstream of PTEN (PMID:8625838, PMID:9806630, PMID:17151361, PMID:15183898). De novo missense mutations at Pro65 of PCGF2 cause Turnpenny-Fry syndrome, a developmental disorder attributed to disruption of PRC1-histone interaction (PMID:30343942).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1993 High

    Cloning of MEL-18 revealed it encodes a nuclear DNA-binding protein with a RING-finger motif, establishing it as a candidate chromatin regulator before its Polycomb group membership was recognized.

    Evidence cDNA cloning, sequence analysis, and chromosomal mapping in human cells

    PMID:8325509

    Open questions at the time
    • No functional assay for transcriptional activity
    • Binding partners unknown
  2. 1995 High

    Demonstration that MEL-18 binds a specific DNA consensus sequence (5'-GACTNGACT-3') and represses transcription directly resolved how MEL-18 could silence target genes including c-myc, bcl-2, and Hox loci.

    Evidence In vitro DNA binding assays and transcriptional reporter assays

    PMID:8521824

    Open questions at the time
    • In vivo relevance of the consensus motif not established
    • No chromatin context tested
  3. 1996 High

    Knockout mice established that MEL-18 is required in vivo to maintain Hox gene silencing, with loss causing posterior homeotic transformations — the first genetic proof of its Polycomb group function in mammals.

    Evidence Homologous recombination knockout mouse with skeletal analysis and Hox gene in situ hybridization

    PMID:8625838

    Open questions at the time
    • Molecular mechanism of Hox silencing (histone modification vs. DNA binding) unresolved
    • Redundancy with Bmi-1 not tested genetically
  4. 1997 High

    Parallel studies showed mel-18 knockout causes severe combined immunodeficiency and that mel-18 negatively regulates B cell proliferation through c-Myc and cell cycle machinery, revealing that its Polycomb function extends to immune cell development and proliferative control.

    Evidence Knockout and transgenic mouse analyses with lymphocyte proliferation assays and double-transgenic epistasis for c-myc

    PMID:9252126 PMID:9806630

    Open questions at the time
    • Whether mel-18 and bmi-1 act in the same complex or in parallel unclear
    • Direct chromatin target genes in lymphocytes not identified
  5. 2001 High

    Discovery that mel-18 deficiency impairs Th2 differentiation through defective IL-4 gene demethylation established a role for PCGF2 in epigenetic regulation of lineage-specific cytokine loci beyond Hox genes.

    Evidence Knockout mouse T cell differentiation assays with IL-4 gene methylation analysis

    PMID:11520462

    Open questions at the time
    • Whether PCGF2 recruits DNA demethylases directly was unknown
    • Mechanism linking PRC1 to DNA methylation changes unresolved
  6. 2004 High

    Gain- and loss-of-function studies demonstrated that mel-18 negatively regulates hematopoietic stem cell self-renewal via Hoxb4 repression, distinguishing its role from BMI-1 which promotes self-renewal.

    Evidence Competitive repopulating unit assays in mel-18 knockout and transgenic mice with Hoxb4 expression analysis

    PMID:15183898

    Open questions at the time
    • Whether PCGF2 and BMI-1 occupy the same versus distinct PRC1 complexes at HSC loci unknown
  7. 2005 Medium

    Identification of cyclin D2 and lamin A/C as PCGF2 interacting partners expanded its potential functions to direct cell cycle regulation and nuclear envelope biology, though functional consequences remained limited.

    Evidence Yeast two-hybrid screens with co-immunoprecipitation validation

    PMID:16182291 PMID:16248985

    Open questions at the time
    • Cyclin D2 interaction awaits in vivo validation beyond yeast two-hybrid
    • Lamin A/C interaction has no demonstrated functional consequence
    • No reciprocal validation for lamin A/C interaction
  8. 2006 High

    ChIP and promoter-reporter studies showed MEL-18 transcriptionally represses BMI-1 by directly binding the BMI-1 promoter, establishing a regulatory hierarchy within the Polycomb system where MEL-18 controls BMI-1 levels.

    Evidence Chromatin immunoprecipitation, promoter-reporter assays, and RNAi knockdown with primary transcript quantification

    PMID:17151361

    Open questions at the time
    • Whether MEL-18 represses BMI-1 through H2AK119ub or another mechanism not dissected
  9. 2007 High

    Reconstitution of the Ring1B/Mel-18 heterodimer as an E3 ubiquitin ligase for H2AK119 monoubiquitylation, dependent on Mel-18 phosphorylation, provided the first biochemical mechanism for PCGF2's chromatin-silencing activity within PRC1.

    Evidence Affinity purification of melPRC1 complex, reconstituted in vitro E3 ligase assay on nucleosomal substrates, phosphorylation site mass spectrometry and mutagenesis

    PMID:17936708

    Open questions at the time
    • Identity of kinases responsible for activating phosphorylation unknown
    • Whether phosphorylation regulation operates in vivo not tested
  10. 2008 High

    Discovery that MEL-18 inhibits global sumoylation by binding UBC9 (SUMO E2) revealed a PRC1-independent biochemical activity, with cell cycle–regulated inhibition of HSF2 and RanGAP1 sumoylation.

    Evidence Co-immunoprecipitation, RNAi/overexpression with sumoylation assays, cell cycle fractionation

    PMID:18211895 PMID:18706886

    Open questions at the time
    • Structural basis of PCGF2-UBC9 interaction unresolved
    • Full substrate scope of anti-SUMO activity unknown
    • RanGAP1 inhibition shown by single lab without independent replication
  11. 2011 Medium

    Multiple studies connected PCGF2 loss to PI3K/Akt pathway activation via PTEN downregulation, HIF-1α/VEGF upregulation, and direct chromatin binding at the Il17a promoter in Th17 cells, broadening its role to angiogenesis and adaptive immunity.

    Evidence Knockdown/overexpression with pathway analysis, ChIP at VEGF and Il17a promoters, xenograft models, T cell differentiation assays

    PMID:21602890 PMID:21674483

    Open questions at the time
    • Whether PTEN is a direct transcriptional target of PCGF2/PRC1 not established
    • ChIP at Il17a shows binding but mechanism of activation (not repression) by a Polycomb protein unexplained
  12. 2013 Medium

    MEL-18 was shown to inhibit epithelial-mesenchymal transition by epigenetically derepressing miR-205, which suppresses ZEB1/ZEB2, linking PRC1 chromatin regulation to microRNA-mediated tumor suppression.

    Evidence miRNA microarray, promoter methylation analysis, ChIP, RNAi/overexpression, xenograft

    PMID:23474752

    Open questions at the time
    • Mechanism by which a Polycomb repressor activates miR-205 transcription remains unclear
    • Single lab finding
  13. 2015 Medium

    MEL-18 was found to regulate ESR1 transcription by inhibiting BMI-1/RING1B-mediated degradation of the SUMO protease SENP1, thereby controlling sumoylation of the ESR1 transactivators p53 and SP1 — integrating its anti-SUMO and PRC1 activities into a single regulatory circuit.

    Evidence SUMOylation assays, Co-IP, ESR1 promoter reporter, xenograft

    PMID:25822021

    Open questions at the time
    • Direct SENP1 ubiquitylation by BMI-1/RING1B not shown with purified components
    • Single lab
  14. 2018 Medium

    Identification of de novo PCGF2 Pro65 missense mutations as the cause of Turnpenny-Fry syndrome established the first human Mendelian disease linked to canonical PRC1 dysfunction.

    Evidence Patient genetic analysis with de novo mutation identification and computational structural modeling

    PMID:30343942

    Open questions at the time
    • Dominant-negative mechanism inferred from modeling but not validated by cellular or biochemical assays
    • Patient cohort small
  15. 2019 Medium

    MEL-18 was shown to epigenetically silence ADAM10/17 sheddases via PRC1/PRC2 cooperation; their derepression upon MEL-18 loss drives ErbB ligand shedding and trastuzumab resistance, providing a translational link to therapy resistance.

    Evidence ChIP, gene expression arrays, ADAM inhibitor rescue, xenograft

    PMID:30265336

    Open questions at the time
    • Whether MEL-18 recruits PRC2 directly or indirectly not resolved
    • Clinical validation lacking
  16. 2022 Medium

    Conditional knockout of Pcgf2 in granulosa cells showed it upregulates progesterone receptor expression via H2AK119ub1 modification at the Pgr promoter, establishing an activating chromatin function for PCGF2/PRC1 in female fertility.

    Evidence Conditional KO mouse, ChIP for H2AK119ub1, hCG stimulation, histological and gene expression analysis

    PMID:36407101

    Open questions at the time
    • Activating role of H2AK119ub1 at Pgr contradicts canonical repressive model — mechanism not explained
    • Single tissue context

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how PCGF2 switches between transcriptional repression and activation at different loci, the structural basis of its UBC9 inhibition, the kinases that phosphorylate PCGF2 to activate its E3 ligase-directing function, and whether its anti-SUMO and PRC1 activities are coordinated or independent in vivo.
  • No structural model of PCGF2-UBC9 complex
  • Kinases activating PCGF2 phosphorylation unidentified
  • Genome-wide distinction between loci repressed versus activated by PCGF2 lacking
  • Relative contribution of anti-SUMO versus PRC1 activity to developmental phenotypes untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0003677 DNA binding 2 GO:0140110 transcription regulator activity 2 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 3
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
BMI1CBX8CCND2HPH2HSF2RING1BUBE2I
Complex memberships
PRC1 (cPRC1.2/melPRC1)

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 MEL-18 (PCGF2) acts as a transcriptional repressor by binding directly to the specific DNA sequence 5'-GACTNGACT-3', found within regulatory regions of genes including c-myc, bcl-2, and Hox genes. In vitro DNA binding assay, transcriptional reporter assays The EMBO journal High 8521824
1993 MEL-18 protein contains a RING-finger motif, a helix-loop-helix (HLH)-like structure, and a Pro/Ser-rich region, and functions as a nuclear DNA-binding protein; the human gene maps to chromosome 12q22. cDNA cloning, sequence analysis, in situ hybridization Gene High 8325509
1996 Mel-18 knockout mice show posterior transformations of the axial skeleton correlated with ectopic expression of Homeobox cluster genes, establishing that Mel-18 maintains silent state of Hox gene expression during paraxial mesoderm development, similar to Bmi-1. Homologous recombination knockout mouse, skeletal analysis, in situ hybridization for Hox gene expression Development High 8625838
1997 Mel-18 negatively regulates cell cycle progression in B cells through a cascade involving c-myc and cdc25; overexpression arrests B cells upon BCR stimulation via downregulation of cyclins D2/E, CDK4/6/7, and CDC25A. c-myc double-transgenic rescue places c-myc downstream of mel-18. Transgenic mouse overexpression, mel-18/c-myc double-transgenic epistasis, CDK activity assays, retinoblastoma phosphorylation analysis Immunity High 9806630
1997 Loss of mel-18 in mice causes severe combined immunodeficiency due to impaired mitotic response of lymphocyte precursors upon IL-7 stimulation; mel-18 and bmi-1 null mice share identical axial skeleton and lymphoid phenotypes, indicating they act in the same genetic cascade. Knockout mouse analysis, lymphocyte proliferation assay, genetic comparison of mel-18 and bmi-1 mutants Immunity High 9252126
2007 MEL-18 forms a polycomb-like complex (melPRC1) containing RING1/2, HPH2, and CBX8. A reconstituted Ring1B/Mel-18 subcomplex functions as an E3 ubiquitin ligase that specifically monoubiquitylates histone H2A at lysine 119 in the context of nucleosomes; Mel-18 directs substrate specificity to H2AK119, and this targeting requires prior phosphorylation of Mel-18 at multiple residues. Affinity purification, reconstituted E3 ligase assay in vitro, mutational analysis, mass spectrometry identification of phosphorylation sites Molecular cell High 17936708
2003 MEL-18 forms homodimers via its N-terminal RING-finger and alpha-helix domains, and homodimerization is regulated by PKC phosphorylation; dephosphorylated Mel-18 is able to homodimerize. In vitro pull-down assay, co-immunoprecipitation in transfected COS-7 cells, deletion analysis, PKC/phosphatase treatment Biochemical and biophysical research communications Medium 12480532
2006 MEL-18 transcriptionally represses Bmi-1 expression by acting on the Bmi-1 promoter, and regulates Bmi-1 levels during senescence via downregulation of c-Myc; knockdown of Mel-18 by RNAi increases Bmi-1 and c-Myc expression. Promoter-reporter assay, chromatin immunoprecipitation, quantitative RT-PCR of primary transcripts, RNA interference Molecular biology of the cell High 17151361
2007 MEL-18 represses Bmi-1 expression in breast cancer cells, and this repression is accompanied by reduction of Akt/PKB activity; constitutively active Akt overrides the tumor-suppressive effect of Mel-18 overexpression, placing Akt downstream of Mel-18/Bmi-1. Overexpression, RNAi knockdown, Akt kinase activity assay, constitutively active Akt rescue experiment Cancer research High 17545584
2008 MEL-18 interacts with HSF2 and inhibits its sumoylation by binding to and inhibiting the SUMO E2 enzyme UBC9; this interaction decreases during mitosis, allowing elevated HSF2 sumoylation. MEL-18 acts as an anti-SUMO E3-like factor. Co-immunoprecipitation, RNAi knockdown and overexpression of MEL-18 with sumoylation assays, cell cycle fractionation The Journal of biological chemistry High 18211895
2008 MEL-18 interacts with RanGAP1 and inhibits its sumoylation independently of the RING domain; RanGAP1 sumoylation decreases during mitosis, associated with increased MEL-18-RanGAP1 interaction at that cell cycle stage. Co-immunoprecipitation, sumoylation assay, RING domain deletion mutant analysis, cell cycle fractionation Biochemical and biophysical research communications Medium 18706886
2008 MEL-18 overexpression in SK-BR-3 breast cancer cells induces G1 arrest via reduction of Akt phosphorylation, leading to decreased cyclin D1 expression (through reduced beta-catenin nuclear localization and TCF/LEF activity) and altered p27(Kip1) phosphorylation at Thr157; this is INK4a/ARF-independent. Overexpression and antisense knockdown, CDK activity assay, cell cycle analysis, TCF/LEF reporter assay, Western blotting Cancer research Medium 18519679
2005 MEL-18 directly interacts with cyclin D2 via its C-terminal proline/serine-rich domain (with the N-terminal region of cyclin D2 being required on the cyclin D2 side); reduction of Mel-18 expression increases proliferative activity in cyclin D2-overexpressing cells. Yeast two-hybrid screen, co-localization imaging, antisense knockdown with proliferation assay FEBS letters Medium 16182291
2001 Mel-18 deficiency in mice impairs Th2 cell differentiation, associated with decreased IL-4 gene demethylation and reduced GATA3 induction, establishing a role for mel-18 in epigenetic regulation of Th2 cytokine gene expression. Knockout mouse, T cell differentiation assay, cytokine production measurement, IL-4 gene methylation analysis Immunity High 11520462
2004 Mel-18 negatively regulates HSC self-renewal; mel-18 knockout mice show increased HSC G0 phase proportion and enhanced self-renewal, associated with elevated Hoxb4 expression; mel-18 transgenic mice show decreased self-renewal activity. Competitive repopulating unit assay in vivo, mel-18 knockout and transgenic mice, flow cytometry cell cycle analysis, quantitative RT-PCR for Hoxb4 Experimental hematology High 15183898
2011 MEL-18 negatively regulates HIF-1α expression and VEGF transcription via the PTEN/PI3K/Akt pathway; MEL-18 loss downregulates PTEN, activating PI3K/Akt/MDM2, which increases HIF-1α protein; MEL-18 also modulates FOXO3a cytoplasmic retention and HIF-1α/CBP complex recruitment to the VEGF promoter. Knockdown and overexpression, Western blotting, luciferase reporter for VEGF promoter, ChIP, xenograft mouse model Oncogene Medium 21602890
2013 MEL-18 negatively regulates EMT by epigenetically increasing miR-205 transcription through inhibition of DNMT-mediated DNA methylation at the miR-205 promoter; increased miR-205 downregulates ZEB1 and ZEB2, maintaining E-cadherin expression. miRNA microarray, promoter methylation analysis, luciferase reporter, ChIP, RNAi/overexpression, xenograft Oncogene Medium 23474752
2012 MEL-18 loss enhances breast cancer stem cell self-renewal by upregulating Jagged-1 (a Notch ligand) through the Wnt/TCF pathway; pharmacological inhibition of Notch and Wnt abrogates Mel-18-knockdown-mediated tumorsphere formation. shRNA knockdown and overexpression, flow cytometry for CSC markers, tumorsphere formation assay, pharmacological pathway inhibition, in vivo xenograft FASEB journal Medium 22954590
2015 MEL-18 drives ESR1 transcription by suppressing SUMOylation of the ESR1 transactivators p53 and SP1; MEL-18 facilitates deSUMOylation by inhibiting BMI-1/RING1B-mediated ubiquitin-proteasomal degradation of SENP1 (SUMO protease). Overexpression and knockdown, SUMOylation assay, Co-IP, ESR1 promoter reporter, xenograft in vivo The Journal of clinical investigation Medium 25822021
2016 PCGF2 interacts directly with UBE2I (SUMO E2) and inhibits UBE2I-mediated sumoylation of PML-RARA; PCGF2 knockdown induces sumoylation-, ubiquitylation-, and PML nuclear body-mediated degradation of PML-RARA. Upon ATO treatment, PCGF2-UBE2I interaction is disrupted, releasing UBE2I to sumoylate PML-RARA. Co-immunoprecipitation, immunofluorescence co-localization, overexpression and knockdown, sumoylation assay Biochimica et biophysica acta Medium 27030546
2011 PCGF2 directly binds to HOXA7 chromatin and represses HOXA7 expression; PCGF2 knockdown derepresses HOXA7 and is sufficient to induce granulocytic differentiation of HL-60 APL cells, placing PCGF2 upstream of HOXA7. Chromatin immunoprecipitation (ChIP), shRNA knockdown, differentiation assays (NBT staining, Wright-Giemsa staining, cell cycle analysis, marker gene expression) Biochemical and biophysical research communications Medium 22085718
2019 MEL-18 epigenetically silences ADAM10 and ADAM17 expression in cooperation with PRC1 and PRC2; MEL-18 loss induces ADAM sheddase-mediated ErbB ligand production and receptor heterodimerization, causing trastuzumab resistance in HER2+ breast cancer. Gene expression microarray, receptor tyrosine kinase array, ChIP, overexpression/knockdown, ADAM inhibitor rescue experiment, in vivo xenograft Journal of the National Cancer Institute Medium 30265336
2018 Missense mutations affecting Pro65 of PCGF2 cause a recognizable human developmental syndrome (Turnpenny-Fry syndrome); structural modeling indicates this residue is in an N-terminal loop critical for histone binding, and mutant PCGF2 may have dominant-negative effects by sequestering PRC1 components into complexes unable to interact with histones. Patient genetic analysis, de novo mutation identification, computational structural modeling American journal of human genetics Medium 30343942
2022 PCGF2 in granulosa cells binds to the progesterone receptor (Pgr) promoter and upregulates Pgr expression after hCG stimulation by modifying H2AK119ub1; GC-specific Pcgf2 knockout in mice causes follicle loss, ovulation defects, and subfertility. Conditional knockout mouse, ChIP for H2AK119ub1, hCG stimulation experiments, histological analysis, gene expression analysis Frontiers in cell and developmental biology Medium 36407101
2005 Loss of mel-18 impairs early T progenitor expansion and is associated with drastically reduced Hes-1 expression (a Notch target gene); mel-18 is required for maintenance of active Hes-1 gene expression, indicating a role in sustaining active chromatin states. Knockout mouse analysis, T progenitor culture and in vitro Delta-like-1 stimulation, quantitative gene expression analysis Journal of immunology Medium 15728456
2011 MEL-18 binds to the Il17a promoter in Th17 cells and positively regulates Il17a and Il17f expression; MEL-18 binding at the Il17a promoter is dependent on TCR signaling, requires continuous TGF-β for maintenance, and correlates with RORγt recruitment. ChIP, RNAi knockdown, T cell differentiation assay, cytokine measurement European journal of immunology Medium 21674483
2005 Novel PCGF2 (Mel-18) interacting partners were identified by yeast two-hybrid screen: Mel-18 interacts with lamin A/C (including progerin); confirmed by co-immunoprecipitation in fibroblasts. Yeast two-hybrid screen, co-immunoprecipitation of endogenous proteins Biochemical and biophysical research communications Low 16248985
2024 The canonical Pcgf2-containing PRC1 complex (cPRC1.2) forms chromatin loops at bivalent promoters in mouse ESCs, keeping them poised but silent; loss of Pcgf2 disrupts these loops and impairs transcriptional induction of genes necessary for neuronal differentiation. CTCF co-localizes at cPRC1.2 loop anchors, and activation involves a switch from cPRC1.2-mediated to CTCF-mediated active loops. CRISPR/Cas9 KO of Pcgf2, Hi-C chromatin conformation analysis, virtual 4C, genomic ChIP analyses, neuronal differentiation assays bioRxivpreprint Medium bio_10.1101_2024.11.13.623456
2024 Deletion of Pcgf2 (canonical PRC1) in neural stem cells causes strong reduction in proliferation and altered lineage fate during both neurogenic and gliogenic phases; genes encoding stem cell and neurogenic factors are bound by PRC1 and differentially expressed upon Pcgf2/4 deletion. Conditional Pcgf2/4 deletion in NSCs, proliferation assays, lineage fate analysis, ChIP, gene expression analysis bioRxivpreprint Medium bio_10.1101_2024.08.07.606990

Source papers

Stage 0 corpus · 52 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 A role for mel-18, a Polycomb group-related vertebrate gene, during theanteroposterior specification of the axial skeleton. Development (Cambridge, England) 233 8625838
2006 Mel-18, a polycomb group protein, regulates cell proliferation and senescence via transcriptional repression of Bmi-1 and c-Myc oncoproteins. Molecular biology of the cell 120 17151361
1995 mel-18, a Polycomb group-related mammalian gene, encodes a transcriptional negative regulator with tumor suppressive activity. The EMBO journal 120 8521824
2007 Mel-18 acts as a tumor suppressor by repressing Bmi-1 expression and down-regulating Akt activity in breast cancer cells. Cancer research 110 17545584
2007 A phosphorylated form of Mel-18 targets the Ring1B histone H2A ubiquitin ligase to chromatin. Molecular cell 108 17936708
2013 Loss of the polycomb protein Mel-18 enhances the epithelial-mesenchymal transition by ZEB1 and ZEB2 expression through the downregulation of miR-205 in breast cancer. Oncogene 105 23474752
2007 Contribution of polycomb homologues Bmi-1 and Mel-18 to medulloblastoma pathogenesis. Molecular and cellular biology 100 17452456
1997 The role of mel-18, a mammalian Polycomb group gene, during IL-7-dependent proliferation of lymphocyte precursors. Immunity 98 9252126
2010 BMI1 and Mel-18 oppositely regulate carcinogenesis and progression of gastric cancer. Molecular cancer 97 20170541
2001 Regulation of Th2 cell differentiation by mel-18, a mammalian polycomb group gene. Immunity 87 11520462
2004 Polycomb group gene mel-18 modulates the self-renewal activity and cell cycle status of hematopoietic stem cells. Experimental hematology 78 15183898
2006 Implication of polycomb members Bmi-1, Mel-18, and Hpc-2 in the regulation of p16INK4a, p14ARF, h-TERT, and c-Myc expression in primary breast carcinomas. Clinical cancer research : an official journal of the American Association for Cancer Research 68 17145810
2011 Loss of Mel-18 induces tumor angiogenesis through enhancing the activity and expression of HIF-1α mediated by the PTEN/PI3K/Akt pathway. Oncogene 58 21602890
1998 mel-18 negatively regulates cell cycle progression upon B cell antigen receptor stimulation through a cascade leading to c-myc/cdc25. Immunity 56 9806630
1993 Cloning and chromosome mapping of the human Mel-18 gene which encodes a DNA-binding protein with a new 'RING-finger' motif. Gene 51 8325509
2005 Novel progerin-interactive partner proteins hnRNP E1, EGF, Mel 18, and UBC9 interact with lamin A/C. Biochemical and biophysical research communications 45 16248985
2012 Loss of Mel-18 enhances breast cancer stem cell activity and tumorigenicity through activating Notch signaling mediated by the Wnt/TCF pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 42 22954590
2008 Mel-18 negatively regulates INK4a/ARF-independent cell cycle progression via Akt inactivation in breast cancer. Cancer research 40 18519679
2005 Polycomb group gene mel-18 regulates early T progenitor expansion by maintaining the expression of Hes-1, a target of the Notch pathway. Journal of immunology (Baltimore, Md. : 1950) 32 15728456
2015 MEL-18 loss mediates estrogen receptor-α downregulation and hormone independence. The Journal of clinical investigation 29 25822021
2009 The novel tumor-suppressor Mel-18 in prostate cancer: its functional polymorphism, expression and clinical significance. International journal of cancer 28 19585577
2010 Expression and clinicopathological significance of Mel-18 and Bmi-1 mRNA in gastric carcinoma. Journal of experimental & clinical cancer research : CR 23 21059209
2018 Missense Mutations of the Pro65 Residue of PCGF2 Cause a Recognizable Syndrome Associated with Craniofacial, Neurological, Cardiovascular, and Skeletal Features. American journal of human genetics 22 30343942
2010 Expression of BMI-1 and Mel-18 in breast tissue--a diagnostic marker in patients with breast cancer. BMC cancer 22 21162745
1995 The Drosophila melanogaster gene lethal(3)73Ah encodes a ring finger protein homologous to the oncoproteins MEL-18 and BMI-1. Gene 22 7590267
2008 MEL-18 interacts with HSF2 and the SUMO E2 UBC9 to inhibit HSF2 sumoylation. The Journal of biological chemistry 20 18211895
2011 Inhibition of PCGF2 enhances granulocytic differentiation of acute promyelocytic leukemia cell line HL-60 via induction of HOXA7. Biochemical and biophysical research communications 18 22085718
2009 Reciprocal expression of Bmi1 and Mel-18 is associated with functioning of primitive hematopoietic cells. Experimental hematology 17 19409954
2003 Dimerization of the Polycomb-group protein Mel-18 is regulated by PKC phosphorylation. Biochemical and biophysical research communications 17 12480532
2010 Id1 enhances RING1b E3 ubiquitin ligase activity through the Mel-18/Bmi-1 polycomb group complex. Oncogene 15 20697353
2011 The binding activity of Mel-18 at the Il17a promoter is regulated by the integrated signals of the TCR and polarizing cytokines. European journal of immunology 12 21674483
2009 Analysis of Mel-18 expression in prostate cancer tissues and correlation with clinicopathologic features. Urologic oncology 12 19395284
2002 Mutation analysis of the mel-18 gene that shows decreased expression in human breast cancer cell lines. Breast cancer (Tokyo, Japan) 12 12196719
2021 Aqueous extract of Solanum nigrum attenuates Angiotensin-II induced cardiac hypertrophy and improves cardiac function by repressing protein kinase C-ζ to restore HSF2 deSUMOlyation and Mel-18-IGF-IIR signaling suppression. Journal of ethnopharmacology 11 34634367
2016 PCGF2 negatively regulates arsenic trioxide-induced PML-RARA protein degradation via UBE2I inhibition in NB4 cells. Biochimica et biophysica acta 10 27030546
2016 Mel-18 negatively regulates stem cell-like properties through downregulation of miR-21 in gastric cancer. Oncotarget 10 27542229
2005 The polycomb group gene product Mel-18 interacts with cyclin D2 and modulates its activity. FEBS letters 10 16182291
2021 Small Molecule Compound Nerolidol attenuates Hypertension induced hypertrophy in spontaneously hypertensive rats through modulation of Mel-18-IGF-IIR signalling. Phytomedicine : international journal of phytotherapy and phytopharmacology 8 33611212
2019 Role of MEL-18 Amplification in Anti-HER2 Therapy of Breast Cancer. Journal of the National Cancer Institute 8 30265336
2008 Mel-18 interacts with RanGAP1 and inhibits its sumoylation. Biochemical and biophysical research communications 8 18706886
1993 The mouse Mel-18 "RING-finger" gene: genomic organization, promoter analysis and chromosomal assignment. DNA sequence : the journal of DNA sequencing and mapping 7 8219280
2014 Expression and clinicopathological significance of Mel-18 mRNA in colorectal cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 5 24964959
2002 Chemokine-mediated thymopoiesis is regulated by a mammalian Polycomb group gene, mel-18. Immunology letters 5 11750047
1997 Suppression of tumor growth by the 3' untranslated region of mel-18 in 3Y1 cells transformed by the E6 and E7 genes of human papillomavirus type 18. Cancer letters 5 9233832
2022 SLCO4A1-AS1 triggers the malignant behaviours of melanoma cells via sponging miR-1306-5p to enhance PCGF2. Experimental dermatology 4 35427425
2022 Polycomb subunit Pcgf2 mediates ovulation and fertility through transcriptional regulation progesterone receptor. Frontiers in cell and developmental biology 4 36407101
2017 Expression and Clinicopathological Significance of Mel-18 and Bmi-1 in Esophageal Squamous Cell Carcinoma. Technology in cancer research & treatment 3 28425347
1996 Cloning and characterization of two transcripts generated from the mel-13 gene positioned adjacent to the mammalian Polycomb group-related gene mel-18. Biochimica et biophysica acta 3 8597592
2024 PCGF2 Acts as an Oncogenic Driver in Colon Cancer through the Upregulation of CENPE. Discovery medicine 2 39327243
2022 Investigation of an inherited PCGF2: p.Pro65Leu mutation causing Turnpenny-Fry syndrome. American journal of translational research 2 36105049
2017 WITHDRAWN: Expression and clinicopathological significance of Mel-18 and Bmi-1 in oesophageal squamous cell carcinoma. Neoplasma 0 28485167
2011 Mel-18 controls the enrichment of tumor-initiating cells in SP fraction in mouse breast cancer. Hiroshima journal of medical sciences 0 21970185