Affinage

PLAG1

Zinc finger protein PLAG1 · UniProt Q6DJT9

Length
500 aa
Mass
55.9 kDa
Annotated
2026-04-28
100 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PLAG1 is a developmentally regulated C2H2 zinc finger transcription factor that controls postnatal growth, fertility, hematopoietic stem cell self-renewal, and neocortical progenitor proliferation. It binds a bipartite DNA consensus (GRGGC-N7-RGGK) through zinc fingers 3, 6, and 7 and directly transactivates target genes including IGF2, MSI2, BCL2, GPX4, and ATG12; its nuclear import depends on karyopherin alpha2 recognition of the NLS1 motif (PMID:10646861, PMID:11882654). PLAG1 transcriptional output is repressed by UBC9/PIAS-mediated SUMOylation at Lys-244/263 and activated by p300-mediated acetylation opposed by HDAC7, and in hematopoietic stem cells PLAG1 maintains quiescence by dampening protein synthesis via 4EBP1 upregulation and miR-127 (PMID:15208321, PMID:16207715, PMID:35639948). Loss-of-function mutations in PLAG1 cause Silver-Russell syndrome, while oncogenic activation occurs predominantly through promoter-swapping gene fusions (CTNNB1-, CHCHD7-, LIFR-, HAS2-, FGFR1-PLAG1) that place the intact coding sequence under constitutively active promoters, driving tumorigenesis in salivary gland, adipose tissue, kidney, and hematopoietic lineages (PMID:28796236, PMID:10029085, PMID:30026293).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1999 High

    The central question of how PLAG1 becomes oncogenic in pleomorphic adenomas was answered: chromosomal translocations swap the PLAG1 promoter with constitutively active promoters (CTNNB1, TCEA1), placing the intact coding region under ectopic transcriptional control.

    Evidence Northern blot, RNase protection, 5'-RACE, RT-PCR, and sequencing of fusion transcripts in human pleomorphic adenomas

    PMID:10029085

    Open questions at the time
    • Whether promoter swapping alone is sufficient for transformation was not tested
    • No functional assay for transformation capacity of the fusions
  2. 2000 High

    Two foundational questions were resolved simultaneously: PLAG1's DNA-binding specificity (bipartite GRGGC-N7-RGGK consensus via zinc fingers 3, 6, and 7) and its first direct transcriptional target (IGF2 P3 promoter), establishing it as a bona fide sequence-specific transcriptional activator; separately, promoter-swapping fusions (HAS2-, COL1A2-PLAG1) were found in lipoblastoma, extending the oncogenic mechanism beyond salivary gland tumors.

    Evidence DNA binding assays with zinc finger mutagenesis, transactivation reporter assays; fusion transcript identification in lipoblastoma

    PMID:10646861 PMID:10987300

    Open questions at the time
    • No structural data for PLAG1-DNA interaction
    • Full spectrum of direct target genes unknown
  3. 2002 High

    The mechanism by which PLAG1 reaches its nuclear site of action was defined: karyopherin alpha2 binds the NLS1 (KRKR) motif to mediate import, with the zinc finger domain providing residual import capacity.

    Evidence Yeast two-hybrid, GST pull-down, NLS mutagenesis, beta-galactosidase nuclear import assay

    PMID:11882654

    Open questions at the time
    • Whether other importin-alpha isoforms contribute in vivo is untested
    • Regulation of import (e.g., by post-translational modification) not explored
  4. 2004 High

    Multiple advances converged: SUMOylation at Lys-244/263 was identified as a repressive post-translational switch for PLAG1 transactivation; genome-wide target identification revealed ~47 induced genes beyond IGF2; Plag1 knockout mice revealed essential roles in postnatal growth and fertility; and PLAG1 was shown to cooperate with CBFbeta-SMMHC to induce AML by promoting G1-S transition in hematopoietic progenitors.

    Evidence In vivo SUMOylation assay with mutagenesis and reporter assays; conditional microarray profiling; Plag1-null mouse phenotyping; retroviral bone marrow transplantation leukemia model

    PMID:14712223 PMID:15208321 PMID:15585652 PMID:15606491

    Open questions at the time
    • SUMOylation-acetylation interplay not yet resolved
    • IGF2 was not reduced in Plag1-null embryos, leaving growth-mediating targets uncertain
    • Direct targets among the 47 microarray hits not confirmed by ChIP
  5. 2005 High

    The opposing post-translational regulatory logic was completed: p300-mediated acetylation activates and HDAC7-mediated deacetylation represses PLAG1; sumoylation-deficient PLAG1 relocalizes to the nucleolus and loses transforming ability, linking post-translational modification to both subcellular compartmentalization and oncogenic function.

    Evidence Acetylation/deacetylation assays, co-transfection with p300/HDAC7, subcellular imaging, transformation assay with SUMO-site mutants

    PMID:16207715

    Open questions at the time
    • Which specific acetylation sites drive activation is not mapped
    • Nucleolar function of PLAG1 is unexplored
  6. 2005 High

    Conditional transgenic overexpression of PLAG1 in murine salivary glands caused pleomorphic adenomas with 100% penetrance and upregulation of Igf2/H19 and Dlk1/Gtl2 imprinted loci, providing direct in vivo proof that PLAG1 is an oncogene sufficient for salivary gland tumorigenesis.

    Evidence Cre/loxP conditional transgenic mouse, histopathology, gene expression profiling

    PMID:15930271

    Open questions at the time
    • Contribution of individual target genes to tumor initiation not dissected
    • Human relevance of Dlk1/Gtl2 upregulation unconfirmed
  7. 2006 High

    Additional fusion partners (CHCHD7-PLAG1 via cryptic 8q rearrangement) and a cross-species transcriptional target (mouse beta-catenin promoter) were identified, broadening the promoter-swapping repertoire and linking PLAG1 to Wnt signaling.

    Evidence Molecular cloning/FISH for CHCHD7-PLAG1 fusion; reporter assay and IHC in transgenic tumors for beta-catenin

    PMID:16108035 PMID:16736500

    Open questions at the time
    • Beta-catenin activation was species-specific (mouse not human promoter), limiting translational relevance
    • CHCHD7-PLAG1 frequency across tumor types not determined
  8. 2008 High

    Genetic epistasis showed Igf2 is necessary but not sufficient for PLAG1-driven tumorigenesis: Igf2 deletion in PLAG1 transgenic mice delayed but did not abolish tumor formation, with Wnt pathway genes remaining upregulated independently of Igf2.

    Evidence Compound Igf2-null/PLAG1-transgenic mice, tumor latency analysis, gene expression profiling

    PMID:18425330

    Open questions at the time
    • Identity of the Igf2-independent oncogenic effectors not fully resolved
    • Whether Wnt activation is direct or indirect not determined
  9. 2009 High

    A post-transcriptional regulatory layer was defined: miR-181a/b, miR-107, and miR-424 directly target the PLAG1 3′ UTR, and their epigenetic silencing via promoter methylation causes PLAG1 overexpression in CLL.

    Evidence 3′ UTR luciferase reporter with site-directed mutagenesis, miRNA profiling, methylation analysis in CLL samples

    PMID:19692702

    Open questions at the time
    • Relative contribution of individual miRNAs to PLAG1 dosage in normal tissues unknown
    • Whether miRNA-mediated derepression is a general mechanism across PLAG1-driven cancers untested
  10. 2017 High

    The physiological HMGA2→PLAG1→IGF2 growth axis was established, and loss-of-function PLAG1 mutations were shown to cause Silver-Russell syndrome; separately, PLAG1 was found to upregulate GDH1 to confer anoikis resistance in LKB1-deficient lung cancer, and Plag1-null male mice showed impaired spermatogenesis with reduced Hsd17b3.

    Evidence Whole-exome sequencing in Silver-Russell syndrome families with functional reporter assays; metabolic/Co-IP assays in lung cancer PDX model; Plag1 KO testis RNA-seq and sperm analysis

    PMID:28706261 PMID:28796236 PMID:29249655

    Open questions at the time
    • Whether PLAG1 directly binds the GDH1 promoter not shown by ChIP
    • Sertoli cell vs. germ cell autonomous requirements of PLAG1 not resolved
  11. 2018 High

    PLAG1's role in stem/progenitor biology was expanded: it co-binds with USF2 at the MSI2 promoter to drive HSPC self-renewal and expansion, and it controls neocortical progenitor proliferation vs. neurogenesis balance during brain development.

    Evidence ChIP-seq, reporter assays, and cord blood HSPC overexpression for MSI2; Plag1 KO and gain-of-function in developing mouse neocortex with BrdU incorporation

    PMID:29641991 PMID:30361413

    Open questions at the time
    • Whether PLAG1-USF2 interaction is direct protein-protein or indirect chromatin co-occupancy not fully resolved
    • Downstream effectors of PLAG1 in neocortical progenitors beyond proliferation not identified
  12. 2018 High

    In Wilms tumor, loss of miRNA processing (DROSHA/DGCR8 mutations) derepresses PLAG1, which drives IGF2 transactivation and mTORC1 signaling to promote neoplastic kidney growth, connecting miRNA biogenesis defects to PLAG1-mediated oncogenesis.

    Evidence In vitro growth assays, in vivo mouse kidney overexpression, ChIP/reporter for IGF2, mTORC1 pathway analysis

    PMID:30026293

    Open questions at the time
    • Whether mTORC1 activation is entirely IGF2-dependent or has independent PLAG1 inputs not resolved
  13. 2022 High

    The mechanism of PLAG1-mediated HSC self-renewal was defined: PLAG1 dampens protein synthesis by upregulating 4EBP1 and miR-127, maintaining HSC dormancy; c-MYC antagonizes this effect, establishing a PLAG1-MYC axis that balances quiescence and activation.

    Evidence Overexpression/knockdown in human cord blood HSCs, xenograft transplantation, ChIP-seq, protein synthesis assays, epistasis with c-MYC

    PMID:35639948

    Open questions at the time
    • Whether PLAG1 directly binds the 4EBP1 promoter or acts indirectly not shown
    • Relationship between PLAG1's HSC dormancy function and its oncogenic proliferative role not reconciled
  14. 2024 Medium

    PLAG1 was shown to directly transactivate GPX4, linking it to ferroptosis resistance and redox homeostasis in hepatocellular carcinoma; the lncRNA PVT1/miRNA axis was identified as an upstream transcriptional regulator of PLAG1 mRNA levels.

    Evidence ChIP assay, RNA immunoprecipitation, dual-luciferase reporter, CRISPR screen in HCC cells

    PMID:38745179

    Open questions at the time
    • Single-lab finding; independent replication needed
    • Whether GPX4 activation by PLAG1 occurs in non-cancer contexts is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how PLAG1 simultaneously promotes HSC quiescence yet drives proliferation in oncogenic contexts; the structural basis of bipartite DNA recognition; the complete direct target gene repertoire across tissues; and the mechanism by which sumoylation-deficient PLAG1 relocalizes to the nucleolus.
  • No structural model of PLAG1-DNA complex exists
  • Context-dependent switch between quiescence-promoting and proliferative functions is mechanistically undefined
  • Nucleolar function of PLAG1 is entirely unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 3 GO:0005730 nucleolus 1
Pathway
R-HSA-1643685 Disease 7 R-HSA-74160 Gene expression (Transcription) 7 R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 1 R-HSA-9612973 Autophagy 1
Partners
EP300HDAC7HMGA2KPNA2PIAS1UBC9USF2

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 PLAG1 is a nuclear protein that binds DNA via a bipartite consensus sequence (GRGGC core and RGGK G-cluster separated by seven random nucleotides), with zinc fingers 6 and 7 interacting with the core and finger 3 with the G-cluster; it functions as a transcription factor that activates transcription from this consensus site and directly binds and activates the IGF-II P3 promoter. DNA binding assays, transient transactivation reporter assays, active-site mutagenesis of zinc fingers Cancer research High 10646861
1999 PLAG1 is activated in pleomorphic adenomas by promoter swapping: chromosomal translocations fuse the constitutively expressed CTNNB1 or TCEA1 (SII) promoter regions to the entire PLAG1 coding sequence, replacing its developmental regulatory elements and driving ectopic PLAG1 expression. Northern blot, RNase protection, 5'-RACE, RT-PCR, nucleotide sequencing Cancer research High 10029085
2000 PLAG1 activation via promoter swapping (with HAS2 or COL1A2 promoters fused to the intact PLAG1 coding sequence) is a central oncogenic event in lipoblastoma, extending PLAG1's tumorigenic role beyond epithelial salivary gland cells. RT-PCR, sequencing of fusion transcripts, promoter-swapping analysis Cancer research High 10987300
2002 PLAG1 nuclear import is mediated by karyopherin alpha2 (importin-alpha), which physically interacts with NLS1 (KRKR motif) of PLAG1; mutation of NLS1 decreases nuclear import, and NLS1 alone can drive nuclear localization of cytoplasmic beta-galactosidase; the zinc finger domain also contributes residual nuclear import. Yeast two-hybrid, GST pull-down, NLS mutagenesis, nuclear import assay with beta-galactosidase reporter The Journal of biological chemistry High 11882654
2004 PLAG1 transactivating capacity is repressed by SUMOylation at lysines Lys-244 and Lys-263; UBC9 and PIAS proteins interact with PLAG1 and mediate SUMO-1 modification; mutation of both SUMO consensus sites significantly increases PLAG1 transactivation capacity. Yeast two-hybrid, GST pull-down, in vivo SUMOylation assay, site-directed mutagenesis of SUMO sites, transactivation reporter assay The Journal of biological chemistry High 15208321
2005 SUMOylation represses and acetylation activates PLAG1 transcriptional activity; PLAG1 is acetylated by p300 and deacetylated/repressed by HDAC7; sumoylation-deficient PLAG1 concentrates in the nucleolus rather than the nucleus; mutation of three sumoylation-site lysines impairs PLAG1 oncogenic transformation ability. In vivo sumoylation assay, acetylation assay, co-transfection with p300/HDAC7, subcellular localization imaging, transformation assay, site-directed mutagenesis The Journal of biological chemistry High 16207715
2004 Microarray analysis identified 47 genes induced and 12 repressed by conditional PLAG1 expression in fetal kidney 293 cells; key upregulated targets include IGF-II and cytokine-like factor 1; many upregulated genes harbor PLAG1 consensus binding motifs in their promoters, consistent with direct transcriptional activation. Conditional inducible PLAG1 expression, oligonucleotide microarray, in silico promoter analysis, comparison with human pleomorphic adenoma expression profiles Oncogene High 14712223
2004 Plag1 and Plagl2 independently cooperate with CBFbeta-SMMHC in vivo to rapidly induce AML in mice; Plag1 promotes G1-to-S transition and expands hematopoietic progenitors, indicating a proliferative mechanism in leukemogenesis. Mouse bone marrow transplantation/retroviral overexpression, in vivo leukemia model, in vitro cell-cycle analysis Blood High 15585652
2004 Targeted disruption of murine Plag1 causes growth retardation (reduced body weight maintained throughout adult life) and reduced fertility in both sexes, establishing Plag1 as required for postnatal growth and reproductive function; Igf2 expression was not significantly affected in Plag1-/- embryos, indicating additional target-gene mechanisms. Plag1 knockout mouse generation, phenotypic analysis (weight, organ size, fertility), Northern blot for Igf2 Development, growth & differentiation High 15606491
2005 Targeted PLAG1 overexpression in murine salivary glands (via MMTV-Cre) causes pleomorphic adenomas with 100% penetrance, with upregulation of Igf2/H19 and Dlk1/Gtl2 imprinted gene clusters in tumors, establishing PLAG1 as a direct in vivo oncogene in salivary tissue. Cre/loxP conditional transgenic mouse model, histopathology, gene expression analysis Cancer research High 15930271
2004 PLAG1 transactivates transcription from the embryonic IGF2 P3 promoter in hepatoblastoma cell lines, as shown by luciferase reporter assays; PLAG1 is overexpressed 3-12-fold in hepatoblastoma compared to normal liver, suggesting PLAG1-driven IGF2 upregulation underlies hepatoblastoma pathogenesis. Quantitative RT-PCR, luciferase reporter assay in hepatoblastoma cell lines Genes, chromosomes & cancer Medium 14695992
2006 A novel CHCHD7-PLAG1 gene fusion is generated by cryptic intrachromosomal 8q rearrangement in pleomorphic adenomas; breakpoints occur in the 5' noncoding region, placing PLAG1 coding sequence under the constitutively active CHCHD7 promoter (promoter substitution), leading to PLAG1 protein overexpression in epithelial, myoepithelial, and mesenchymal-like tumor cells. Molecular cloning, Northern blot, Western blot, immunohistochemistry, FISH on nuclear chromatin fibers Genes, chromosomes & cancer High 16736500
2007 Ring chromosomes derived from chromosome 8 in pleomorphic adenomas consistently generate novel FGFR1-PLAG1 gene fusions in which the 5'-part of FGFR1 is linked to the PLAG1 coding sequence, revealing a mechanism by which ring formation activates PLAG1 by promoter substitution. Spectral karyotyping, FISH, array CGH, molecular fusion analysis Oncogene Medium 18059337
2006 PLAG1 activates transcription of mouse (but not human) beta-catenin, a key Wnt signaling component, via four PLAG1 consensus binding sites in the mouse beta-catenin promoter; PLAG1 transgenic mouse salivary gland tumors show upregulation of beta-catenin and c-myc at the protein level. Reporter assay (cotransfection with beta-catenin promoter construct), immunohistochemistry, transgenic mouse model, sequence analysis of PLAG1 binding sites International journal of cancer Medium 16108035
2008 Inactivation of Igf2 in PLAG1 transgenic mice (P1-MCre) significantly delays but does not fully abrogate salivary gland tumor development, demonstrating that Igf2 is a required but not sole mediator of PLAG1 oncogenesis; Wnt signaling genes (Wnt6, Cyclin D1, beta-catenin) are upregulated independently of Igf2 in PLAG1 tumors. Genetic epistasis in Igf2-null/PLAG1-transgenic compound mice, gene expression analysis International journal of oncology High 18425330
2009 miR-181a, miR-181b, miR-107, and miR-424 directly regulate PLAG1 protein expression by binding to the 3' UTR of PLAG1 mRNA; luciferase reporter assays with site-directed mutagenesis of binding sites confirmed this regulation; epigenetic silencing of these miRNAs via promoter methylation leads to PLAG1 protein overexpression in CLL. Luciferase reporter assay, site-directed mutagenesis of miRNA binding sites, miRNA expression profiling, methylation analysis, Western blot Blood High 19692702
2017 PLAG1 upregulates GDH1 expression upon cell detachment; GDH1-derived alpha-KG activates CamKK2 by enhancing AMPK binding to CamKK2, providing energy production that confers anoikis resistance in LKB1-deficient lung cancer; HMGA2 regulates IGF2 expression through PLAG1. Loss-of-function experiments, metabolic assays, co-immunoprecipitation, patient-derived xenograft model Molecular cell High 29249655
2017 HMGA2 regulates IGF2 expression through PLAG1 (and in a PLAG1-independent manner); loss-of-function mutations in PLAG1 cause Silver-Russell syndrome with fetal and postnatal growth restriction, establishing the HMGA2-PLAG1-IGF2 axis as a physiological growth regulatory pathway. Whole-exome sequencing, targeted sequencing, functional reporter assays linking HMGA2, PLAG1, and IGF2 Genetics in medicine High 28796236
2018 PLAG1 and USF2 co-bind the MSI2 promoter and cooperatively drive transcription of MSI2 in human hematopoietic stem and progenitor cells; co-overexpression of PLAG1 and USF2 expands CD34+ cells in vitro, phenocopying direct MSI2 overexpression; ChIP-seq confirms preferential co-binding of PLAG1 and USF2 at MSI2 and other HSPC homeostasis genes. ChIP-seq, luciferase reporter assay, co-immunoprecipitation, loss-of-function (siRNA), overexpression in cord blood HSPCs Stem cell reports High 29641991
2018 Mutations in microRNA processing genes (e.g., DROSHA, DGCR8) in Wilms tumors cause derepression of PLAG1 protein (a miRNA target); PLAG1 overexpression accelerates Wilms tumor cell growth in vitro and induces neoplastic kidney growth in vivo by transactivating IGF2 and driving mTORC1 signaling. In vitro growth assays, in vivo mouse kidney overexpression model, ChIP/reporter assays for IGF2 transactivation, mTORC1 pathway analysis Genes & development High 30026293
2022 PLAG1 is essential for long-term human HSC self-renewal; PLAG1 dampens protein synthesis through upregulation of 4EBP1 and translation-targeting miR-127, restraining cell growth and division; PLAG1's pro-self-renewal effects are attenuated by c-MYC overexpression; ChIP-seq shows genome-wide chromatin occupancy at HSC homeostasis gene regulatory regions. Overexpression and knockdown in human cord blood HSCs, xenograft transplantation, ChIP-seq, RNA-seq, protein synthesis assays, epistasis with c-MYC Blood High 35639948
2016 PLAG1 functions as a transcription factor that reinforces BCL2 promoter activity, causing BCL2 upregulation at the mRNA level; miR-424 and miR-27a target the 3' UTR of PLAG1 to suppress its expression, and knockdown of PLAG1 sensitizes AML cells to TRAIL-induced apoptosis via reduced BCL2 and enhanced caspase cleavage. Luciferase reporter assay (BCL2 promoter), 3' UTR reporter assays, PLAG1 knockdown, apoptosis/caspase assays Oncotarget Medium 27013583
2014 HMGA2 acts as an upstream transcriptional activator of PLAG1: transient HMGA2 overexpression in MCF-7 cells increases PLAG1 mRNA within 24-48 hours, and FGF1-induced HMGA2 stimulation in adipose stem cells simultaneously increases PLAG1 mRNA; all uterine leiomyomas with HMGA2 overexpression show concurrent PLAG1 activation without chromosome 8 abnormalities. Transient transfection/overexpression, quantitative RT-PCR, correlation analysis in human tumors PloS one Medium 24516594
2012 PLAG1 binding to the IGF2 P3 promoter and subsequent IGF2 activation are cell-type specific; ChIP reveals endogenous PLAG1 occupancy at the IGF2 P3 promoter in Hep3B but not JEG-3 cells; the H19 imprinting control region insulator modulates the cell-context dependence of PLAG1-driven IGF2 P3 promoter activity. Chromatin immunoprecipitation (ChIP), GFP reporter/insulator assay, zinc-inducible stable PLAG1-expressing JEG-3 clones, FACS International journal of oncology Medium 23023303
2017 PLAG1 deficiency in male mice causes significantly reduced daily sperm production, impaired sperm motility, and sloughing of the germinal epithelium; PLAG1 is expressed in Sertoli cells and sparse germ cells; PLAG1 loss downregulates spermatogenesis genes and Hsd17b3 (key androgen biosynthesis enzyme) and upregulates immune and epididymis-specific genes in the testis. Plag1 knockout mice, X-gal staining for localization, RNA-seq transcriptomics, sperm count and motility analysis, testicular histology Scientific reports High 28706261
2024 PLAG1 drives expression of GPX4 (glutathione peroxidase 4) at the transcriptional level, contributing to redox homeostasis and ferroptosis resistance in hepatocellular carcinoma cells; PLAG1 is regulated at the transcriptional level by the lncRNA PVT1 acting as a competing endogenous RNA for miRNAs; sorafenib reduces PLAG1 mRNA (not protein stability or ubiquitination) via the PVT1/miRNA axis. ChIP assay, RNA immunoprecipitation, dual-luciferase reporter assay, ubiquitination assay, CRISPR screening, tissue microarray Journal of experimental & clinical cancer research Medium 38745179
2020 PLAG1 acts as a transcription factor that promotes ATG12 expression; circPOFUT1 sequesters miR-488-3p to de-repress PLAG1, which then drives ATG12-mediated autophagy and chemoresistance in gastric cancer cells. Luciferase reporter assay, RNA immunoprecipitation, overexpression/knockdown, autophagy assays, in vivo xenograft Cell death & disease Medium 36624091
2018 Plag1 is required for normal neocortical progenitor proliferation: in Plag1 single-mutant mouse neocortices, progenitors proliferate less and produce more neurons prematurely; in gain-of-function studies, Plag1 overexpression reduces neurogenesis and increases BrdU uptake (enhanced proliferation with delayed kinetics compared to Plagl2). Plag1 knockout and gain-of-function in developing mouse neocortex, BrdU incorporation assay, neurogenesis analysis Biology open Medium 30361413
2001 PLAG1 protein is localized to nuclei of outer layer cells of tubulo-ductal structures (putative progenitor basal duct cells) in pleomorphic adenomas, with variable expression reflecting differentiation stage; cytogenetic/immunohistochemical co-analysis confirmed clonal common origin of immunophenotypically diverse tumor cells all carrying the PLAG1 rearrangement. Immunohistochemistry combined with FISH on the same tumor sections, co-analysis of PLAG1 protein and cytogenetic abnormalities Laboratory investigation Medium 11555676

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 The PLAG1-GDH1 Axis Promotes Anoikis Resistance and Tumor Metastasis through CamKK2-AMPK Signaling in LKB1-Deficient Lung Cancer. Molecular cell 264 29249655
2011 Variants modulating the expression of a chromosome domain encompassing PLAG1 influence bovine stature. Nature genetics 238 21516082
2000 PLAG1 fusion oncogenes in lipoblastoma. Cancer research 185 10987300
2000 PLAG1, the main translocation target in pleomorphic adenoma of the salivary glands, is a positive regulator of IGF-II. Cancer research 152 10646861
2007 PLAG1, the prototype of the PLAG gene family: versatility in tumour development (review). International journal of oncology 129 17332914
2005 PLAG1 gene alterations in salivary gland pleomorphic adenoma and carcinoma ex-pleomorphic adenoma: a combined study using chromosome banding, in situ hybridization and immunocytochemistry. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 128 15920557
2009 miRNA deregulation by epigenetic silencing disrupts suppression of the oncogene PLAG1 in chronic lymphocytic leukemia. Blood 123 19692702
1999 Conserved mechanism of PLAG1 activation in salivary gland tumors with and without chromosome 8q12 abnormalities: identification of SII as a new fusion partner gene. Cancer research 123 10029085
2013 Frequent PLAG1 gene rearrangements in skin and soft tissue myoepithelioma with ductal differentiation. Genes, chromosomes & cancer 113 23630011
2004 Plag1 and Plagl2 are oncogenes that induce acute myeloid leukemia in cooperation with Cbfb-MYH11. Blood 111 15585652
2017 Genetic disruption of the oncogenic HMGA2-PLAG1-IGF2 pathway causes fetal growth restriction. Genetics in medicine : official journal of the American College of Medical Genetics 106 28796236
2004 Microarray screening for target genes of the proto-oncogene PLAG1. Oncogene 105 14712223
2001 PLAG1 alterations in lipoblastoma: involvement in varied mesenchymal cell types and evidence for alternative oncogenic mechanisms. The American journal of pathology 101 11549588
2011 Aberrant PLAG1 expression in pleomorphic adenomas of the salivary gland: a molecular genetic and immunohistochemical study. Virchows Archiv : an international journal of pathology 91 21394649
2013 Evidence for pleiotropism and recent selection in the PLAG1 region in Australian Beef cattle. Animal genetics 87 23909810
2006 CHCHD7-PLAG1 and TCEA1-PLAG1 gene fusions resulting from cryptic, intrachromosomal 8q rearrangements in pleomorphic salivary gland adenomas. Genes, chromosomes & cancer 81 16736500
2004 Amplification and overexpression of the IGF2 regulator PLAG1 in hepatoblastoma. Genes, chromosomes & cancer 81 14695992
2015 Emerging role of PLAG1 as a regulator of growth and reproduction. The Journal of endocrinology 80 26577933
2012 PLAG1 alteration in carcinoma ex pleomorphic adenoma: immunohistochemical and fluorescence in situ hybridization studies of 22 cases. Head and neck pathology 75 22485045
2017 PLAG1 immunohistochemistry is a sensitive marker for pleomorphic adenoma: a comparative study with PLAG1 genetic abnormalities. Histopathology 74 28796899
2004 Targeted disruption of the murine Plag1 proto-oncogene causes growth retardation and reduced fertility. Development, growth & differentiation 73 15606491
2019 Novel PLAG1 Gene Rearrangement Distinguishes a Subset of Uterine Myxoid Leiomyosarcoma From Other Uterine Myxoid Mesenchymal Tumors. The American journal of surgical pathology 71 30489320
2005 Salivary gland tumors in transgenic mice with targeted PLAG1 proto-oncogene overexpression. Cancer research 71 15930271
2016 Subsets of salivary duct carcinoma defined by morphologic evidence of pleomorphic adenoma, PLAG1 or HMGA2 rearrangements, and common genetic alterations. Cancer 69 27379604
2011 Genetic variation in PLAG1 associates with early life body weight and peripubertal weight and growth in Bos taurus. Animal genetics 65 22497486
2021 Molecular Profiling of Clear Cell Myoepithelial Carcinoma of Salivary Glands With EWSR1 Rearrangement Identifies Frequent PLAG1 Gene Fusions But No EWSR1 Fusion Transcripts. The American journal of surgical pathology 61 33027073
2013 miR-141 contributes to fetal growth restriction by regulating PLAG1 expression. PloS one 60 23554918
2013 An analysis of PLAG1 and HMGA2 rearrangements in salivary duct carcinoma and examination of the role of precursor lesions. Histopathology 58 23738717
2001 Histologic localization of PLAG1 (pleomorphic adenoma gene 1) in pleomorphic adenoma of the salivary gland: cytogenetic evidence of common origin of phenotypically diverse cells. Laboratory investigation; a journal of technical methods and pathology 58 11555676
2007 High-resolution array CGH analysis of salivary gland tumors reveals fusion and amplification of the FGFR1 and PLAG1 genes in ring chromosomes. Oncogene 57 18059337
2000 Evidence of involvement of the PLAG1 gene in lipoblastomas. International journal of oncology 55 10811981
2014 Diagnostic utility of PLAG1 immunohistochemical determination in salivary gland tumors. Applied immunohistochemistry & molecular morphology : AIMM 53 23958548
2014 Identification of COL3A1 and RAB2A as novel translocation partner genes of PLAG1 in lipoblastoma. Genes, chromosomes & cancer 53 24700772
2024 PLAG1 interacts with GPX4 to conquer vulnerability to sorafenib induced ferroptosis through a PVT1/miR-195-5p axis-dependent manner in hepatocellular carcinoma. Journal of experimental & clinical cancer research : CR 46 38745179
2020 Lipoblastomas presenting in older children and adults: analysis of 22 cases with identification of novel PLAG1 fusion partners. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 44 33097826
2008 Upregulation of Igf and Wnt signalling associated genes in pleomorphic adenomas of the salivary glands in PLAG1 transgenic mice. International journal of oncology 44 18425330
2017 Functional confirmation of PLAG1 as the candidate causative gene underlying major pleiotropic effects on body weight and milk characteristics. Scientific reports 43 28322319
2020 NDRG1-PLAG1 and TRPS1-PLAG1 Fusion Genes in Chondroid Syringoma. Cancer genomics & proteomics 42 32345665
2006 Wnt pathway is involved in pleomorphic adenomas induced by overexpression of PLAG1 in transgenic mice. International journal of cancer 42 16108035
2017 A PLAG1 mutation contributed to stature recovery in modern cattle. Scientific reports 41 29215042
2018 Clinicopathological effect of PLAG1 fusion genes in pleomorphic adenoma and carcinoma ex pleomorphic adenoma with special emphasis on histological features. Histopathology 40 30307055
2015 SLIT2/ROBO1-miR-218-1-RET/PLAG1: a new disease pathway involved in Hirschsprung's disease. Journal of cellular and molecular medicine 40 25786906
2011 PLAG1 expression in mesenchymal tumors: an immunohistochemical study with special emphasis on the pathogenetical distinction between soft tissue myoepithelioma and pleomorphic adenoma of the salivary gland. Pathology international 40 22192798
2016 Loss of expression of Plag1 in malignant transformation from pleomorphic adenoma to carcinoma ex pleomorphic adenoma. Human pathology 38 27473265
2020 Function and characterization of the promoter region of perilipin 1 (PLIN1): Roles of E2F1, PLAG1, C/EBPβ, and SMAD3 in bovine adipocytes. Genomics 36 31981700
2018 DNA methylation-mediated repression of miR-181a/135a/302c expression promotes the microsatellite-unstable colorectal cancer development and 5-FU resistance via targeting PLAG1. Journal of genetics and genomics = Yi chuan xue bao 36 29735329
2018 Mutations in microRNA processing genes in Wilms tumors derepress the IGF2 regulator PLAG1. Genes & development 36 30026293
2013 Comparison of the effects explained by variations in the bovine PLAG1 and NCAPG genes on daily body weight gain, linear skeletal measurements and carcass traits in Japanese Black steers from a progeny testing program. Animal science journal = Nihon chikusan Gakkaiho 36 23607392
2018 Recurrent rearrangements of the PLAG1 and HMGA2 genes in lacrimal gland pleomorphic adenoma and carcinoma ex pleomorphic adenoma. Acta ophthalmologica 35 29437290
2016 Genome-Wide Association Study Reveals the PLAG1 Gene for Knuckle, Biceps and Shank Weight in Simmental Beef Cattle. PloS one 32 27997562
2005 Sumoylation and acetylation play opposite roles in the transactivation of PLAG1 and PLAGL2. The Journal of biological chemistry 32 16207715
2013 A novel PLAG1-RAD51L1 gene fusion resulting from a t(8;14)(q12;q24) in a case of lipoblastoma. Cancer genetics 30 23890983
2004 Repression of the Transactivating Capacity of the Oncoprotein PLAG1 by SUMOylation. The Journal of biological chemistry 30 15208321
2023 Circular RNA circPOFUT1 enhances malignant phenotypes and autophagy-associated chemoresistance via sequestrating miR-488-3p to activate the PLAG1-ATG12 axis in gastric cancer. Cell death & disease 29 36624091
2021 Methylation and Expression of FTO and PLAG1 Genes in Childhood Obesity: Insight into Anthropometric Parameters and Glucose-Lipid Metabolism. Nutrients 28 34063412
2020 Pediatric fibromyxoid soft tissue tumor with PLAG1 fusion: A novel entity? Genes, chromosomes & cancer 28 33300192
2015 Development of Monoclonal Antibody LpMab-10 Recognizing Non-glycosylated PLAG1/2 Domain Including Thr34 of Human Podoplanin. Monoclonal antibodies in immunodiagnosis and immunotherapy 28 26492619
2014 Correlated expression of HMGA2 and PLAG1 in thyroid tumors, uterine leiomyomas and experimental models. PloS one 28 24516594
2011 PLAG1 expression in cutaneous mixed tumors: an immunohistochemical and molecular genetic study. Virchows Archiv : an international journal of pathology 27 21927843
2002 Identification of a karyopherin alpha 2 recognition site in PLAG1, which functions as a nuclear localization signal. The Journal of biological chemistry 27 11882654
2020 Differential Expression of PLAG1 in Apocrine and Eccrine Cutaneous Mixed Tumors: Evidence for Distinct Molecular Pathogenesis. The American Journal of dermatopathology 26 30839344
2019 Identification of a novel BOC-PLAG1 fusion gene in a case of lipoblastoma. Biochemical and biophysical research communications 26 30857637
2018 Detection of 19-bp deletion within PLAG1 gene and its effect on growth traits in cattle. Gene 25 29913240
2020 Hsa-circRNA-103809 Promotes Hepatocellular Carcinoma Development via MicroRNA-1270/PLAG1 Like Zinc Finger 2 Axis. Digestive diseases and sciences 24 32683589
2019 Metastasizing Pleomorphic Adenoma: Recurrent PLAG1/HMGA2 Rearrangements and Identification of a Novel HMGA2-TMTC2 Fusion. The American journal of surgical pathology 24 31094927
2018 PLAG1 and USF2 Co-regulate Expression of Musashi-2 in Human Hematopoietic Stem and Progenitor Cells. Stem cell reports 24 29641991
2018 Expression of PTEN, Androgen Receptor, HER2/neu, Cytokeratin 5/6, Estrogen Receptor-Beta, HMGA2, and PLAG1 in Salivary Duct Carcinoma. Head and neck pathology 24 30390196
2017 PLAG1 deficiency impairs spermatogenesis and sperm motility in mice. Scientific reports 24 28706261
2016 MiR-424 and miR-27a increase TRAIL sensitivity of acute myeloid leukemia by targeting PLAG1. Oncotarget 24 27013583
2016 Expression and Clinical Significance of miR-26a and Pleomorphic Adenoma Gene 1 (PLAG1) in Invasive Pituitary Adenoma. Medical science monitor : international medical journal of experimental and clinical research 23 28012286
2012 Cell type and context-specific function of PLAG1 for IGF2 P3 promoter activity. International journal of oncology 23 23023303
2008 MMTV-cre-mediated fur inactivation concomitant with PLAG1 proto-oncogene activation delays salivary gland tumorigenesis in mice. International journal of oncology 23 18425334
2024 SOX10-Internal Tandem Duplications and PLAG1 or HMGA2 Fusions Segregate Eccrine-Type and Apocrine-Type Cutaneous Mixed Tumors. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 22 38266920
2022 PLAG1 dampens protein synthesis to promote human hematopoietic stem cell self-renewal. Blood 22 35639948
2021 PLAG1-rearrangment in a uterine leiomyosarcoma with myxoid stroma and heterologous differentiation. Genes, chromosomes & cancer 22 34184333
2018 PLAG1, SOX10, and Myb Expression in Benign and Malignant Salivary Gland Neoplasms. Journal of pathology and translational medicine 22 30424592
2019 Assessment of HMGA2 and PLAG1 rearrangements in breast adenomyoepitheliomas. NPJ breast cancer 21 30675516
2015 Undifferentiated myxoid lipoblastoma with PLAG1-HAS2 fusion in an infant; morphologically mimicking primitive myxoid mesenchymal tumor of infancy (PMMTI)--diagnostic importance of cytogenetic and molecular testing and literature review. Cancer genetics 21 26701195
2019 Genome-wide association study identifies the PLAG1-OXR1 region on BTA14 for carcass meat yield in cattle. Physiological genomics 20 30925123
2018 Plag1 and Plagl2 have overlapping and distinct functions in telencephalic development. Biology open 20 30361413
2020 Activation of PLAG1 and HMGA2 by gene fusions involving the transcriptional regulator gene NFIB. Genes, chromosomes & cancer 19 32654217
2018 A novel SNP of PLAG1 gene and its association with growth traits in Chinese cattle. Gene 19 30580072
2007 Heterogeneity of PLAG1 gene rearrangements in pleomorphic adenoma. Cancer genetics and cytogenetics 19 17693184
2021 Novel morphologic findings in PLAG1-rearranged soft tissue tumors. Genes, chromosomes & cancer 18 33893698
2020 Recent advances in smooth muscle tumors with PGR and PLAG1 gene fusions and myofibroblastic uterine neoplasms. Genes, chromosomes & cancer 18 33230916
2016 PLAG1: An Immunohistochemical Marker with Limited Utility in Separating Pleomorphic Adenoma from Other Basaloid Salivary Gland Tumors. Acta cytologica 18 27463119
2008 aP2-Cre-mediated expression activation of an oncogenic PLAG1 transgene results in cavernous angiomatosis in mice. International journal of oncology 18 18097540
2022 3'RNA and whole-genome sequencing of archival uterine leiomyomas reveal a tumor subtype with chromosomal rearrangements affecting either HMGA2, HMGA1, or PLAG1. Genes, chromosomes & cancer 17 35822448
2021 Some pleomorphic adenomas of the breast share PLAG1 rearrangements with the analogous tumour of the salivary glands. Histopathology 16 34292619
1999 Fluorescence in situ hybridization mapping of breakpoints in pleomorphic adenomas with 8q12-13 abnormalities identifies a subgroup of tumors without PLAG1 involvement. Genes, chromosomes & cancer 16 9892112
2020 PLAG1 silencing promotes cell chemosensitivity in ovarian cancer via the IGF2 signaling pathway. International journal of molecular medicine 15 31922228
2019 Bayesian Modeling Identifies PLAG1 as a Key Regulator of Proliferation and Survival in Rhabdomyosarcoma Cells. Molecular cancer research : MCR 15 31757836
2012 Rearrangement of HMGA2 in a case of infantile lipoblastoma without Plag1 alteration. Pediatric blood & cancer 15 22223189
2020 Novel Variant in PLAG1 in a Familial Case with Silver-Russell Syndrome Suspicion. Genes 14 33291420
2019 A SNP in PLAG1 is associated with body height trait in Chinese cattle. Animal genetics 14 31643102
2010 Critical role of microRNAs in chronic lymphocytic leukemia: overexpression of the oncogene PLAG1 by deregulated miRNAs. Leukemia & lymphoma 14 20687796
2008 Adenomyoepitheliomatous lesions of the mammary glands in transgenic mice with targeted PLAG1 overexpression. International journal of cancer 14 18649356
2007 PLAG1 activation in lipoblastoma coinciding with low-level amplification of a derivative chromosome 8 with a deletion del(8)(q13q21.2). Cytogenetic and genome research 14 18160779
2021 Indel mutations of sheep PLAG1 gene and their associations with growth traits. Animal biotechnology 13 33825658
2019 The PLAG1 mRNA expression analysis among genetic variants and relevance to growth traits in Chinese cattle. Animal biotechnology 12 31253059