Affinage

Showing PCGF2 — MEL-18 is a alias.

PCGF2

Polycomb group RING finger protein 2 · UniProt P35227

Length
344 aa
Mass
37.8 kDa
Annotated
2026-06-10
52 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PCGF2 (MEL-18) is a Polycomb group RING-finger protein that operates as a core subunit of canonical PRC1 to enforce chromatin-based transcriptional silencing controlling axial patterning, cell-fate decisions, and proliferation (PMID:8625838, PMID:17936708). Within a melPRC1 complex containing RING1/2, HPH2, and CBX8, PCGF2 directs the Ring1B E3 ubiquitin ligase to monoubiquitylate nucleosomal histone H2A specifically at lysine 119, a substrate-targeting function requiring prior phosphorylation of PCGF2 (PMID:17936708); this PRC1 activity loops bivalent promoters and represses target genes including the Hox cluster, with genetic loss causing posterior homeotic transformation and ectopic Hox expression [PMID:8625838, PMID:bio_10.1101_2024.11.13.623456]. PCGF2 also acts as a sequence-specific transcriptional repressor binding 5'-GACTNGACT-3' in regulatory regions of c-myc, bcl-2, and Hox genes (PMID:8521824), and it homodimerizes through its N-terminal RING and alpha-helix domains in a phosphorylation-regulated manner (PMID:12480532). It restrains cell-cycle progression through a c-Myc/CDC25 cascade and through PI3K/Akt-cyclin D1/p27 signaling, and it transcriptionally represses Bmi-1, thereby limiting self-renewal and driving senescence (PMID:9806630, PMID:17151361, PMID:18519679). Independent of chromatin, PCGF2 sequesters the SUMO E2 enzyme UBC9/UBE2I to inhibit SUMOylation of substrates including HSF2, RanGAP1, and PML-RARA (PMID:18211895, PMID:18706886, PMID:27030546). Across multiple cancers PCGF2 behaves as a tumor suppressor by repressing Bmi-1, HIF-1α/VEGF, and EMT programs and by controlling ESR1 expression (PMID:17151361, PMID:21602890, PMID:23474752, PMID:25822021), and it is required for HSC self-renewal restraint, T-cell differentiation, and granulosa-cell folliculogenesis (PMID:9806630, PMID:11520462, PMID:36407101). De novo missense mutations at Pro65 of PCGF2 cause Turnpenny-Fry syndrome (PMID:30343942).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1993 Medium

    Establishing the molecular nature of MEL-18 was the first step: defining it as a nuclear RING-finger protein placed it among chromatin-associated regulators rather than cytoplasmic effectors.

    Evidence cDNA cloning, sequence analysis, and in situ hybridization mapping to 12q22

    PMID:8325509

    Open questions at the time
    • Domain function not tested
    • No binding partners or substrates identified
    • No functional assay
  2. 1995 Medium

    The question of how MEL-18 acts on genes was first answered by showing it is a sequence-specific DNA-binding repressor, suggesting a direct route to target-gene silencing.

    Evidence In vitro DNA binding and transcriptional reporter assays defining the 5'-GACTNGACT-3' motif

    PMID:8521824

    Open questions at the time
    • In vivo occupancy at endogenous loci not shown
    • Relationship to PRC1 silencing unresolved
    • Repression cofactors unknown
  3. 1996 High

    Genetic knockout established MEL-18 as a bona fide Polycomb group gene required to maintain Hox silencing during axial patterning, anchoring its developmental function.

    Evidence Homologous-recombination knockout mice with skeletal analysis and Hox in situ hybridization

    PMID:8625838

    Open questions at the time
    • Molecular mechanism of silencing not defined
    • Complex membership not yet established
    • Direct vs indirect Hox regulation unclear
  4. 1998 High

    Knockout and double-transgenic epistasis answered how MEL-18 controls proliferation, placing c-Myc downstream in a cell-cycle-restraining cascade and linking it genetically to bmi-1.

    Evidence Transgenic and double-transgenic mice with CDK assays, Western blotting, flow cytometry; epistasis with bmi-1 mutants

    PMID:9252126 PMID:9806630

    Open questions at the time
    • Direct vs indirect c-Myc regulation not resolved here
    • Chromatin mechanism not addressed
    • Tissue specificity of cascade unclear
  5. 2004 High

    Reciprocal gain/loss-of-function in stem and progenitor cells established MEL-18 as a negative regulator of self-renewal acting through defined Hox/Notch targets, extending its role from patterning to cell-fate maintenance.

    Evidence Knockout/transgenic mice, competitive repopulation, RT-PCR for Hoxb4 (HSC) and Hes-1/Notch in T progenitors; IL-4/GATA3 demethylation in Th2

    PMID:11520462 PMID:15183898 PMID:15728456

    Open questions at the time
    • Whether effects are PRC1-dependent not directly tested
    • Direct chromatin binding at these loci not all shown
    • Mechanism of epigenetic memory undefined
  6. 2006 High

    Direct demonstration that MEL-18 represses Bmi-1 transcription clarified the seemingly paradoxical relationship between two PcG genes and linked MEL-18 to senescence and tumor suppression.

    Evidence Promoter-reporter, ChIP, RT-PCR, RNAi, and overexpression in human fibroblasts

    PMID:17151361

    Open questions at the time
    • Whether repression is PRC1-mediated not resolved
    • Contribution of direct vs c-Myc-dependent route not quantified
  7. 2007 High

    Biochemical reconstitution answered the central mechanistic question of MEL-18's enzymatic role: it forms a PRC1-like complex and directs the Ring1B E3 ligase to monoubiquitylate H2AK119, with this targeting requiring MEL-18 phosphorylation.

    Evidence Affinity purification/MS, in vitro reconstitution of E3 ligase activity on nucleosomes, mutational and phosphorylation mapping

    PMID:17936708

    Open questions at the time
    • Kinases responsible for required phosphorylation not identified
    • Genome-wide targeting rules not defined
    • Structural basis of H2AK119 specificity unresolved
  8. 2008 High

    Discovery of UBC9 sequestration revealed a chromatin-independent activity: MEL-18 inhibits SUMOylation of specific substrates, with cell-cycle-modulated interactions explaining mitotic SUMOylation changes.

    Evidence Reciprocal Co-IP, gain/loss-of-function, and in vitro SUMOylation assays for HSF2 and RanGAP1; domain mapping

    PMID:18211895 PMID:18706886

    Open questions at the time
    • Full substrate repertoire unknown
    • How UBC9 sequestration is regulated mechanistically unclear
    • Relationship to PRC1 function not integrated
  9. 2013 Medium

    A series of cancer studies established MEL-18 as a tumor suppressor acting through multiple downstream axes—Akt/Bmi-1, HIF-1α/VEGF angiogenesis, and miR-205/ZEB-driven EMT.

    Evidence Knockdown/overexpression with pathway readouts, ChIP, DNA-methylation analysis, reporter assays, and xenografts in breast cancer models

    PMID:17545584 PMID:21602890 PMID:22954590 PMID:23474752

    Open questions at the time
    • Direct vs indirect targets not fully separated
    • Reliance on single-lab breast cancer models
    • In vivo causal hierarchy among axes unresolved
  10. 2016 Medium

    Extending the SUMO-inhibitory role, MEL-18 was shown to control SUMOylation of disease-relevant substrates (PML-RARA) and of ERα transactivators, linking the activity to leukemia therapy response and estrogen-dependent breast cancer.

    Evidence Co-IP, immunofluorescence, SUMOylation/ubiquitylation assays, reporter assays, and xenografts; ATO disruption of the PCGF2-UBE2I interaction

    PMID:25822021 PMID:27030546

    Open questions at the time
    • Generalizability beyond tested substrates unknown
    • Structural basis of UBE2I inhibition undefined
    • Balance between chromatin and SUMO functions in vivo unclear
  11. 2018 Low

    Human genetics tied PCGF2 to a defined developmental disorder, with recurrent Pro65 missense changes proposed to act dominant-negatively on PRC1-histone engagement.

    Evidence De novo missense mutations in 13 Turnpenny-Fry syndrome patients with computational structural modeling

    PMID:30343942

    Open questions at the time
    • Dominant-negative mechanism is modeled, not experimentally confirmed
    • Effect on H2AK119ub not measured
    • Genotype-phenotype mechanism untested in cells
  12. 2024 Medium

    Genomic and conditional-knockout studies refined the chromatin function, showing cPRC1.2 forms loops at bivalent promoters and controls neural/granulosa-cell fate via locus-specific H2AK119ub rather than global ubiquitylation.

    Evidence Conditional knockout (folliculogenesis/Pgr), CRISPR knockout in ESCs/NSCs, Hi-C, ChIP-seq for H2AK119ub1 and CTCF, RNA-seq

    PMID:36407101 PMID:bio_10.1101_2024.08.07.606990 PMID:bio_10.1101_2024.11.13.623456

    Open questions at the time
    • Two ESC/NSC studies are preprints
    • Mechanism of loop formation vs ubiquitylation not separated
    • How CTCF and cPRC1.2 anchors interconvert undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PCGF2's chromatin (PRC1/H2AK119ub) and chromatin-independent (UBC9 sequestration, sequence-specific repression) activities are coordinated, and which kinases license its substrate-targeting phosphorylation, remain unresolved.
  • No unifying model integrating PRC1 and SUMO-inhibitory roles
  • Kinases controlling MEL-18 phosphorylation unidentified
  • Structural basis of H2AK119 targeting and Pro65 dysfunction unsolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 3 GO:0042393 histone binding 2 GO:0140096 catalytic activity, acting on a protein 2 GO:0003677 DNA binding 1 GO:0016874 ligase activity 1
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1640170 Cell Cycle 2 R-HSA-4839726 Chromatin organization 2
Partners
CBX8CYCLIN D2HSF2LAMIN A/CPML-RARARANGAP1RING1BUBE2I
Complex memberships
canonical PRC1 (cPRC1.2)melPRC1 (Ring1B/Mel-18/HPH2/CBX8)

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 MEL-18 (PCGF2) acts as a sequence-specific transcriptional repressor via direct binding to the DNA sequence 5'-GACTNGACT-3', found in regulatory regions of c-myc, bcl-2, and Hox genes. In vitro DNA binding assays and transcriptional reporter assays The EMBO journal Medium 8521824
1993 The MEL-18 (PCGF2) protein contains a RING-finger motif, a helix-loop-helix (HLH)-like structure, and a Pro/Ser-rich region, and the protein localizes to the nucleus. The human gene maps to chromosome 12q22. cDNA cloning, sequence analysis, in situ hybridization Gene Medium 8325509
1996 Mel-18 knockout mice display posterior homeotic transformations of the axial skeleton with ectopic expression of Hox cluster genes, establishing Mel-18 (PCGF2) as a Polycomb group gene required to maintain Hox gene silencing in paraxial mesoderm. Homologous recombination knockout mice, skeletal analysis, in situ hybridization for Hox gene expression Development (Cambridge, England) High 8625838
1997 Mel-18 (PCGF2) loss-of-function results in severe combined immunodeficiency due to impaired mitotic response of lymphocyte precursors to IL-7 stimulation; the identical phenotype in mel-18 and bmi-1 mutants places them in the same genetic cascade controlling cell cycle progression in the immune system. Knockout mice, lymphocyte proliferation assays, genetic epistasis (mel-18 vs bmi-1 mutant comparison) Immunity High 9252126
1998 Mel-18 (PCGF2) negatively regulates cell cycle progression via a c-Myc/CDC25 cascade; overexpression arrests B cells at G1 with downregulation of c-Myc, cyclins D2/E, and CDKs, and this arrest is rescued in mel-18/c-myc double-transgenic mice, placing c-Myc downstream of Mel-18. Transgenic mice, double-transgenic epistasis, Western blotting, CDK activity assays, flow cytometry Immunity High 9806630
2001 Mel-18 (PCGF2) is required for Th2 cell differentiation; mel-18 knockout T cells show defective IL-4 gene demethylation and reduced GATA3 induction, placing Mel-18 upstream of epigenetic remodeling at the IL-4 locus during Th2 polarization. Knockout mice, cytokine production assays, DNA methylation analysis, GATA3 expression analysis Immunity High 11520462
2003 Mel-18 (PCGF2) forms homodimers requiring the N-terminal RING-finger and alpha-helix domains; homodimerization is regulated by phosphorylation state, with dephosphorylated Mel-18 able to homodimerize, and this is controlled by PKC and phosphatases. In vitro pull-down assays, co-immunoprecipitation in transfected COS-7 cells, deletion analysis, PKC inhibitor/phosphatase experiments Biochemical and biophysical research communications Medium 12480532
2004 Mel-18 (PCGF2) negatively regulates hematopoietic stem cell self-renewal; mel-18 knockout HSCs show elevated Hoxb4 expression, increased G0 phase proportion, and enhanced long-term reconstitution activity, while mel-18 transgenic mice show the opposite. Knockout and transgenic mice, competitive repopulation assays, quantitative RT-PCR for Hoxb4, cell cycle analysis Experimental hematology High 15183898
2005 Mel-18 (PCGF2) supports early T progenitor expansion by maintaining Hes-1 expression, a Notch pathway target; mel-18 knockout early T progenitors fail to maintain Notch-induced Hes-1 expression, placing Mel-18 as a required epigenetic memory component for Notch-driven transcription. Knockout mice, in vivo and in vitro T progenitor assays, quantitative RT-PCR for Hes-1, Delta-like-1 co-culture Journal of immunology Medium 15728456
2005 Mel-18 (PCGF2) directly interacts with cyclin D2 via its C-terminal proline/serine-rich domain (P/S domain), and Mel-18 inhibits cyclin D2 activity; knockdown of Mel-18 in cyclin D2-overexpressing cells increases proliferative activity. Yeast two-hybrid screen, co-localization studies, deletion mapping, antisense knockdown with proliferation assay FEBS letters Medium 16182291
2005 MEL-18 (PCGF2) was identified as a novel lamin A/C-interacting protein by yeast two-hybrid; co-immunoprecipitation of endogenous proteins did not show differential binding between normal and progerin (HGPS mutant lamin A), indicating no unique interaction with progerin. Yeast two-hybrid, co-immunoprecipitation of endogenous proteins Biochemical and biophysical research communications Low 16248985
2006 Mel-18 (PCGF2) transcriptionally represses Bmi-1 expression, and this repression of Bmi-1 by Mel-18 mediates accelerated cellular senescence and shortening of replicative lifespan; Mel-18 also down-regulates c-Myc, which in turn controls Bmi-1 expression. Promoter-reporter assays, chromatin immunoprecipitation, quantitative RT-PCR, RNA interference, overexpression in human fibroblasts Molecular biology of the cell High 17151361
2007 MEL-18 (PCGF2) forms a PRC1-like complex (melPRC1) containing RING1/2, HPH2, and CBX8; a reconstituted Ring1B/Mel-18 subcomplex functions as an E3 ubiquitin ligase that ubiquitylates histone H2A specifically at lysine 119 in nucleosomes, with Ring1B providing E3 catalytic activity and Mel-18 directing specificity to H2AK119 in chromatin. This substrate-targeting function requires prior phosphorylation of Mel-18 at multiple residues. Affinity purification/mass spectrometry, in vitro reconstitution of E3 ligase activity, nucleosome ubiquitylation assay, mutational analysis, phosphorylation mapping Molecular cell High 17936708
2007 Mel-18 (PCGF2) represses Bmi-1 expression and consequently down-regulates Akt/PKB activity in breast cancer cells; constitutively active Akt overrides the tumor-suppressive effect of Mel-18, placing Akt downstream of the Mel-18→Bmi-1 axis. Overexpression, RNA interference knockdown, Akt kinase activity assays, constitutively active Akt rescue experiments Cancer research Medium 17545584
2007 Bmi-1 and Mel-18 (PCGF2) form complexes with overlapping protein compositions in cancer cells, and their knockdown produces similar effects on medulloblastoma cell proliferation and tumor formation, suggesting shared functional roles in cancer cell growth. Proteomics-based complex characterization, shRNA knockdown, clonogenic survival, anchorage-independent growth, xenograft tumor formation Molecular and cellular biology Medium 17452456
2008 MEL-18 (PCGF2) interacts with HSF2 and inhibits HSF2 sumoylation by binding to and inhibiting the SUMO E2 enzyme UBC9; MEL-18 overexpression decreases and RNAi-mediated knockdown increases HSF2 sumoylation. The MEL-18/HSF2 interaction decreases during mitosis, explaining elevated mitotic HSF2 sumoylation. Co-immunoprecipitation, overexpression, RNA interference, in vitro sumoylation assays The Journal of biological chemistry High 18211895
2008 MEL-18 (PCGF2) interacts with RanGAP1 and inhibits its sumoylation independently of the Mel-18 RING domain; RanGAP1 sumoylation decreases during mitosis concomitant with increased MEL-18/RanGAP1 interaction. Co-immunoprecipitation, sumoylation assays, cell cycle fractionation, domain deletion analysis Biochemical and biophysical research communications Medium 18706886
2008 Mel-18 (PCGF2) negatively regulates cell cycle G1-S progression in breast cancer through the PI3K/Akt pathway via cyclin D1 down-regulation and p27(Kip1) phosphorylation at Thr157, independent of INK4a/ARF genes; Mel-18 reduces Akt phosphorylation at Ser473, inhibits GSK-3β phosphorylation, reduces β-catenin nuclear localization, and lowers TCF/LEF promoter activity. Overexpression, antisense knockdown, flow cytometry, CDK activity assays, Western blotting, luciferase reporter assays Cancer research Medium 18519679
2011 PCGF2 (Mel-18) binds directly to HOXA7 chromatin and represses HOXA7 expression, acting upstream of HOXA7 in PRC1-mediated suppression of granulocytic differentiation in HL-60 cells; PCGF2 silencing de-represses HOXA7 and is sufficient to induce granulocytic differentiation. shRNA knockdown, chromatin immunoprecipitation (ChIP), differentiation marker assays, NBT staining, cell cycle analysis, overexpression of HOXA7 Biochemical and biophysical research communications Medium 22085718
2011 Mel-18 (PCGF2) negatively regulates HIF-1α protein level and VEGF transcription via the PTEN/PI3K/Akt/MDM2 pathway; Mel-18 loss downregulates PTEN, activates PI3K/Akt/MDM2, increases HIF-1α, and retains FOXO3a in the cytoplasm, promoting HIF-1α/CBP complex recruitment to the VEGF promoter and tumor angiogenesis. Knockdown, overexpression, Western blotting, luciferase reporter assays, tube formation assays, in vivo xenograft experiments with microvessel density quantification Oncogene Medium 21602890
2011 Mel-18 (PCGF2) binding at the Il17a promoter positively regulates IL-17a and IL-17f expression in Th17 cells; Mel-18 binding is inducible, dependent on TCR signaling, requires continuous TGF-β for maintenance, and correlates with RORγt recruitment to the Il17a promoter. Chromatin immunoprecipitation (ChIP), RNAi knockdown, cytokine expression assays European journal of immunology Medium 21674483
2012 Mel-18 (PCGF2) loss activates Wnt/TCF-mediated upregulation of Jagged-1 (a Notch ligand) and consequently activates Notch signaling to expand breast cancer stem cells; Mel-18 knockdown enriches CD44+/CD24−/ESA+ CSC populations and increases self-renewal, while pharmacologic inhibition of Notch or Wnt abrogates these effects. shRNA knockdown, overexpression, side population assay, tumorsphere formation, in vivo tumor-initiating assay, pharmacologic pathway inhibition FASEB journal Medium 22954590
2013 Mel-18 (PCGF2) epigenetically regulates miR-205 transcription by inhibiting DNMT-mediated DNA methylation of the miR-205 promoter; Mel-18 loss promotes DNA methylation at this locus, reducing miR-205, which de-represses ZEB1 and ZEB2, promoting EMT and reducing E-cadherin expression in breast cancer cells. miRNA microarray, ChIP, DNA methylation analysis (bisulfite/DNMT inhibition), overexpression, knockdown, xenograft experiments Oncogene Medium 23474752
2015 MEL-18 (PCGF2) suppresses SUMOylation of ESR1 transactivators p53 and SP1, driving ESR1 transcription; MEL-18 facilitates deSUMOylation by inhibiting BMI-1/RING1B-mediated ubiquitin-proteasomal degradation of SENP1 (a SUMO protease). Loss of MEL-18 leads to ER-α downregulation and estrogen-independent breast cancer growth. Overexpression, knockdown, SUMOylation assays, ubiquitination assays, promoter reporter assays, in vivo xenograft experiments The Journal of clinical investigation Medium 25822021
2016 PCGF2 (Mel-18) directly interacts with UBE2I (the SUMO E2) and inhibits UBE2I-mediated sumoylation of PML-RARA; PCGF2 knockdown alone is sufficient to induce sumoylation-, ubiquitylation- and PML-NB-mediated degradation of PML-RARA, and ATO treatment disrupts the PCGF2-UBE2I interaction, allowing UBE2I to access PML-RARA. Co-immunoprecipitation, immunofluorescence, overexpression, knockdown, sumoylation assays, ubiquitylation assays Biochimica et biophysica acta Medium 27030546
2018 Missense mutations at Pro65 of PCGF2 cause a developmental syndrome (Turnpenny-Fry syndrome); computational structural modeling suggests the Pro65 substitutions alter an N-terminal loop critical for histone binding, potentially exerting dominant-negative effects by sequestering PRC1 components into complexes that cannot efficiently interact with histones. Clinical genetics (de novo missense mutations in 13 patients), computer structural modeling American journal of human genetics Low 30343942
2019 MEL-18 (PCGF2) epigenetically silences ADAM10/17 expression in cooperation with PRC1 and PRC2; MEL-18 loss de-represses ADAM10/17, increasing ADAM sheddase-mediated ErbB ligand production and receptor heterodimerization, thereby causing trastuzumab resistance in HER2+ breast cancer cells. Gene expression microarray, RTK array, shRNA knockdown, overexpression, in vivo xenograft experiments, FISH for MEL-18 amplification, pharmacologic ADAM inhibitor combination experiments Journal of the National Cancer Institute Medium 30265336
2022 PCGF2 is required in granulosa cells for folliculogenesis and ovulation; PCGF2 binds the progesterone receptor (Pgr) promoter and upregulates Pgr expression by modifying H2AK119ub1 following hCG stimulation, and GC-specific Pcgf2 knockout mice show follicle loss, ovulation defects, and subfertility. Conditional knockout mice, ChIP for PCGF2 promoter binding, H2AK119ub1 chromatin immunoprecipitation, qRT-PCR for Pgr and downstream targets, histological analysis Frontiers in cell and developmental biology High 36407101
2024 The canonical Pcgf2-containing PRC1 complex (cPRC1.2) forms chromatin loops at bivalent promoters in mouse ESCs; loss of Pcgf2 disrupts these loops without affecting global H2AK119ub1 levels and impairs transcriptional induction of neuronal differentiation genes; CTCF is enriched at cPRC1.2 loop anchors, and neuronal differentiation involves a transition from cPRC1.2-mediated to CTCF-mediated active loops. CRISPR/Cas9 knockout in mouse ESCs, Hi-C chromatin conformation analysis, virtual 4C, ChIP-seq for H2AK119ub1 and CTCF, RNA-seq, neuronal differentiation assays bioRxivpreprint Medium bio_10.1101_2024.11.13.623456
2024 Canonical PRC1 containing Pcgf2/4 (cPRC1.2/1.4) plays a dominant role over non-canonical PRC1 (Pcgf3/5) in regulating neural stem cell (NSC) proliferation and lineage fate; Pcgf2/4 deletion leads to strong reduction in NSC proliferation and altered neurogenic and gliogenic fate, with stem cell and neurogenic factor genes directly bound by PRC1 and differentially expressed upon deletion. CRISPR/Cas9 deletion in NSCs, side-by-side comparison of Pcgf2/4 vs Pcgf3/5 knockouts, RNA-seq, PRC1 ChIP-seq, proliferation and differentiation assays 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) 234 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 88 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 59 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 30 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
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 12 34634367
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
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
2022 SLCO4A1-AS1 triggers the malignant behaviours of melanoma cells via sponging miR-1306-5p to enhance PCGF2. Experimental dermatology 5 35427425
2022 Polycomb subunit Pcgf2 mediates ovulation and fertility through transcriptional regulation progesterone receptor. Frontiers in cell and developmental biology 5 36407101
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
2024 PCGF2 Acts as an Oncogenic Driver in Colon Cancer through the Upregulation of CENPE. Discovery medicine 3 39327243
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
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

Missed literature

Know a paper Affinage missed for PCGF2? Flag it for the maintainers and the community.

No submissions yet.