Affinage

PLAG1

Zinc finger protein PLAG1 · UniProt Q6DJT9

Length
500 aa
Mass
55.9 kDa
Annotated
2026-06-10
100 papers in source corpus 32 papers cited in narrative 33 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

PLAG1 is a developmentally regulated, DNA-binding transcription factor that controls cell proliferation, survival, and organismal growth by activating target gene programs centered on insulin-like growth factor signaling (PMID:10646861, PMID:15606491, PMID:28796236). It binds a bipartite consensus sequence (GRGGC core plus a downstream G-cluster separated by ~6–8 nucleotides) through zinc fingers 3, 6, and 7, and uses this activity to transactivate the IGF2/IGF-II P3 promoter and other targets enriched for the same motif (PMID:10646861, PMID:14712223). Nuclear function depends on karyopherin alpha2-mediated import via the NLS1 (KRKR) sequence, and transcriptional output is set by competing post-translational modifications—SUMOylation at Lys-244/Lys-263/Lys-353 represses activity (and mislocalizes the protein to the nucleolus when lost), while p300-mediated acetylation activates it and HDAC7 reverses this (PMID:11882654, PMID:15208321, PMID:16207715). A recurrent theme across normal and malignant tissues is PLAG1 dysregulation: in pleomorphic adenoma, lipoblastoma, and related tumors it is ectopically overexpressed through promoter-swapping fusions that place its coding sequence under constitutively active partner promoters (CTNNB1, TCEA1, CHCHD7, FGFR1, HAS2, COL1A2), and it is also activated downstream of HMGA2 or derepressed by loss of inhibitory microRNAs (PMID:10029085, PMID:10987300, PMID:16736500, PMID:18059337, PMID:24516594, PMID:19692702). Functionally, PLAG1 drives growth through IGF2-dependent activation of AKT/MAPK and mTORC1 signaling, reinforces survival by transcribing BCL2 and the ferroptosis suppressor GPX4, and mediates metabolic adaptation via GDH1; genetic models show it is required for postnatal growth, spermatogenesis, neocortical progenitor balance, and cooperates with CBFbeta-SMMHC to induce acute myeloid leukemia (PMID:30026293, PMID:27013583, PMID:38745179, PMID:29249655, PMID:15606491, PMID:28706261, PMID:30361413, PMID:15585652). In human hematopoietic stem cells PLAG1 promotes self-renewal by restraining protein synthesis through 4EBP1 and miR-127 and co-activates MSI2 with USF2 (PMID:35639948, PMID:29641991). Loss-of-function PLAG1 mutations cause Silver-Russell syndrome with fetal growth restriction (PMID:28796236).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2000 High

    Established PLAG1's core molecular identity by defining its sequence-specific DNA-binding mode and its first direct target, answering how an oncogenic transcription factor engages chromatin.

    Evidence In vitro DNA-binding and zinc-finger mutagenesis with transactivation reporters and IGF-II P3 promoter binding

    PMID:10646861

    Open questions at the time
    • Genome-wide binding repertoire not yet defined
    • Cofactor requirements for transactivation unknown
  2. 2000 High

    Showed that PLAG1 oncogenicity arises chiefly from deregulated expression rather than coding mutation, by identifying promoter-swapping fusions that drive ectopic expression across distinct tumor types.

    Evidence 5'-RACE, RT-PCR, sequencing of fusion transcripts in pleomorphic adenoma and lipoblastoma (CTNNB1, TCEA1, HAS2, COL1A2)

    PMID:10029085 PMID:10987300

    Open questions at the time
    • Whether overexpression alone is sufficient for transformation not addressed
    • Downstream effector program not mapped
  3. 2002 High

    Defined how PLAG1 reaches the nucleus, identifying the NLS1 element and its import receptor required for function.

    Evidence Yeast two-hybrid, GST pull-down, NLS mutagenesis, and nuclear import reporter assays

    PMID:11882654

    Open questions at the time
    • Regulation of import in different cell states unknown
    • Contribution of zinc-finger-mediated residual import not quantified
  4. 2005 High

    Resolved how PLAG1 transcriptional output is tuned, showing opposing control by repressive SUMOylation and activating p300 acetylation/HDAC7 deacetylation, linking modification state to subcellular localization and transforming capacity.

    Evidence In vivo SUMOylation and acetylation assays, lysine mutagenesis, localization, and transformation assays

    PMID:15208321 PMID:16207715

    Open questions at the time
    • Signals controlling the SUMO/acetyl switch unknown
    • SUMO ligases acting on PLAG1 not identified
  5. 2004 Medium

    Defined the PLAG1 target gene program genome-wide and confirmed motif-driven regulation, anchoring IGF-II as a principal output.

    Evidence Oligonucleotide microarray on conditional PLAG1 cells with in silico promoter motif analysis and tumor-profile concordance

    PMID:14712223

    Open questions at the time
    • Direct vs indirect targets not separated by binding data
    • Restricted to one cell context
  6. 2005 High

    Provided direct in vivo proof that PLAG1 overexpression is tumorigenic and activates imprinted growth loci, moving beyond correlative fusion data.

    Evidence Cre/loxP conditional PLAG1 transgenic mice with histopathology and Igf2/H19, Dlk1/Gtl2 expression analysis

    PMID:15930271

    Open questions at the time
    • Mechanism of imprinted cluster activation unresolved
    • Cell-of-origin contributions not dissected
  7. 2008 High

    Tested the causal weight of IGF2 in PLAG1 tumorigenesis, revealing IGF2 is important but not solely responsible and implicating parallel Wnt signaling.

    Evidence Genetic epistasis (Igf2 inactivation on PLAG1-transgenic background) with tumor latency and target gene profiling

    PMID:18425330

    Open questions at the time
    • Relative contribution of Wnt vs residual IGF signaling unquantified
    • Direct PLAG1 regulation of human Wnt targets unproven
  8. 2004 High

    Defined PLAG1's physiological roles and IGF2-independent functions using a clean knockout, distinguishing developmental requirement from its canonical IGF2 axis.

    Evidence Targeted Plag1 disruption in mice with growth, organ-weight, and Igf2 expression analysis; AML cooperation model with CBFbeta-SMMHC

    PMID:15585652 PMID:15606491

    Open questions at the time
    • Identity of Igf2-independent growth effectors unknown
    • Tissue-specific target programs not defined
  9. 2009 High

    Showed PLAG1 is controlled post-transcriptionally, with microRNA loss derepressing PLAG1 protein independent of mRNA level, expanding the routes to its overexpression in cancer.

    Evidence miRNA profiling, 3'UTR luciferase reporters with mutagenesis, Western blot, and miRNA promoter methylation analysis in CLL

    PMID:19692702

    Open questions at the time
    • Whether PLAG1 derepression is driver or passenger in CLL not established
    • Downstream consequences in B cells not defined
  10. 2014 High

    Placed PLAG1 downstream of HMGA2, establishing an HMGA2-PLAG1-IGF2 axis that explains PLAG1 activation in tumors lacking chromosome 8 rearrangements.

    Evidence HMGA2 and FGF1 stimulation with qRT-PCR in MCF-7 and stem cells, plus leiomyoma correlation; later WES of Silver-Russell families with functional pathway validation

    PMID:24516594 PMID:28796236

    Open questions at the time
    • Direct HMGA2 binding at the PLAG1 locus not shown
    • Mechanism of HMGA2-driven PLAG1 transcription unresolved
  11. 2017 High

    Broadened PLAG1 effector biology beyond growth, demonstrating metabolic (GDH1/AMPK anti-anoikis) and developmental (spermatogenesis) functions through distinct target genes.

    Evidence Knockdown/overexpression, co-IP, metabolic assays and PDX for GDH1; Plag1 knockout testis RNA-seq and sperm phenotyping

    PMID:28706261 PMID:29249655

    Open questions at the time
    • Direct PLAG1 binding at GDH1 and spermatogenesis loci not all confirmed
    • Context-specificity of metabolic axis unknown
  12. 2018 High

    Established PLAG1 as a regulator of stem/progenitor identity, mapping genome-wide occupancy and cooperative MSI2 activation with USF2 and a tumorigenic role in Wilms tumor via IGF2-mTORC1.

    Evidence ChIP-seq, reporter assays, cord blood and Wilms tumor in vitro/in vivo growth models

    PMID:29641991 PMID:30026293 PMID:30361413

    Open questions at the time
    • Determinants of PLAG1-USF2 cooperativity not defined
    • How the same factor expands progenitors yet restrains self-renewal elsewhere unresolved
  13. 2024 Medium

    Connected PLAG1 to therapy resistance, showing transcriptional activation of survival/anti-ferroptosis genes (GPX4, BCL2) that modulate response to apoptotic and ferroptotic drugs.

    Evidence ChIP and luciferase reporter for GPX4/BCL2 promoters, knockdown with drug-sensitivity assays in HCC and AML; bovine myoblast/adipocyte PI3K-Akt and PLIN1 studies

    PMID:27013583 PMID:31981700 PMID:35325183 PMID:38745179

    Open questions at the time
    • Generality of the resistance phenotype across tumor types unproven
    • Direct binding confirmed for some but not all survival targets
  14. 2022 High

    Defined a translational-control mechanism for PLAG1 in human HSCs, showing it dampens protein synthesis via 4EBP1 and miR-127 to enforce self-renewal, opposed by c-MYC.

    Evidence Genome-wide ChIP occupancy, RNA-seq, HSC functional assays, protein synthesis measurement, and c-MYC epistasis

    PMID:35639948

    Open questions at the time
    • How PLAG1 toggles between pro-proliferative and translation-restraining programs unknown
    • Direct vs indirect regulation of 4EBP1/miR-127 not fully separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • What determines whether PLAG1 acts as a growth-promoting oncogene versus a self-renewal-enforcing, translation-restraining regulator in a given cell remains unresolved.
  • No unified model linking modification state, cofactor availability (USF2), and context-specific target selection
  • Structural basis of bipartite DNA recognition not solved
  • Mechanism by which the same factor restrains vs promotes proliferation not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 3
Localization
GO:0005634 nucleus 2 GO:0005730 nucleolus 1
Pathway
R-HSA-1643685 Disease 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 2
Partners
EP300HDAC7KPNA2USF2

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 PLAG1 is a nuclear protein that binds DNA in a sequence-specific manner via a bipartite consensus sequence (GRGGC core + RGGK G-cluster separated by 7 random nucleotides); DNA binding is mediated mainly by zinc fingers 3, 6, and 7. PLAG1 activates transcription from this consensus site and directly binds the IGF-II P3 promoter, stimulating IGF-II expression. DNA binding assays, transient transactivation assays, zinc finger mutagenesis, promoter binding studies Cancer research High 10646861
1999 PLAG1 is activated in pleomorphic adenomas by promoter swapping with constitutively expressed partner genes (CTNNB1/beta-catenin, TCEA1/SII), where fusions in the 5' noncoding region exchange regulatory elements and drive ectopic PLAG1 expression. This mechanism operates even in tumors with grossly normal karyotypes via cryptic rearrangements. Northern blot, RNase protection, 5'-RACE, RT-PCR, nucleotide sequencing Cancer research High 10029085
2000 PLAG1 is activated in lipoblastoma via promoter-swapping events fusing the HAS2 or COL1A2 gene promoter to the PLAG1 coding sequence, driving ectopic PLAG1 overexpression in a non-epithelial tumor context. Cytogenetics, RT-PCR, promoter fusion analysis Cancer research High 10987300
2002 PLAG1 is imported into the nucleus via interaction with karyopherin alpha2 (importin-alpha2). The NLS1 sequence (KRKR) in PLAG1 is essential for physical interaction with karyopherin alpha2 and for nuclear import; the zinc finger domain also contributes to residual nuclear import independently of NLS1. Yeast two-hybrid, GST pull-down assay, 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 Lys-244 and Lys-263. Mutation of both SUMO consensus sites inhibits SUMOylation and significantly increases PLAG1 transactivation; SUMO-1-modified forms of PLAG1 (single and double) were detected endogenously. In vivo SUMOylation assay, site-directed mutagenesis of SUMO consensus sites, transactivation reporter assays, anti-PLAG1 immunoblot The Journal of biological chemistry High 15208321
2005 PLAG1 is regulated by both SUMOylation (repressive) and acetylation (activating). PLAG1 is acetylated and activated by p300 and deacetylated and repressed by HDAC7. A conserved transcriptional repression domain depends on three sumoylation motifs; sumoylation at Lys-244, Lys-263, and Lys-353 inhibits PLAG1-induced IGF-II expression. Sumoylation-deficient PLAG1 localizes to the nucleolus rather than the nucleus. Mutation of the three sumoylation-site lysines significantly impairs PLAG1 transformation ability. In vivo sumoylation assay, acetylation assay with p300/HDAC7 overexpression, reporter assays, subcellular localization, transformation assay The Journal of biological chemistry High 16207715
2004 PLAG1 microarray analysis identified 47 induced and 12 repressed target genes upon conditional induction in fetal kidney 293 cells. Major upregulated targets include IGF-II and cytokine-like factor 1; the consensus PLAG1 binding motif GRGGC(N)6-8GGG was enriched in promoters of upregulated genes. Concordance with pleomorphic adenoma expression profiles identified 12 consistent PLAG1 target genes. Oligonucleotide microarray of ~12,000 genes in conditional PLAG1 expression cell lines, in silico promoter analysis Oncogene Medium 14712223
2004 Plag1 and Plagl2 independently cooperate with CBFbeta-SMMHC in vivo to induce acute myeloid leukemia with short latency in mice. Plag1 promotes G1-to-S phase transition and expands hematopoietic progenitors in vitro. In vivo mouse leukemia model, in vitro proliferation and cell cycle assays Blood High 15585652
2004 Targeted disruption of murine Plag1 causes postnatal growth retardation and reduced fertility in both male and female mice. Plag1-/- mice have proportionally smaller organs except for disproportionally small seminal vesicles and ventral prostate. Igf2 expression is not affected in Plag1-/- embryos, suggesting Plag1 regulates postnatal growth through Igf2-independent mechanisms as well. Targeted gene disruption, growth measurement, organ weight analysis, Northern blot for Igf2 Development, growth & differentiation High 15606491
2005 Conditional PLAG1 overexpression in salivary and mammary glands of transgenic mice induces pleomorphic adenomas with upregulation of the Igf2/H19 and Dlk1/Gtl2 imprinted gene clusters, establishing a direct in vivo tumorigenic role for PLAG1. 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 demonstrated by luciferase reporter assays, linking PLAG1 overexpression to IGF2 upregulation in hepatoblastoma. Luciferase reporter assay in hepatoblastoma cell lines, real-time RT-PCR Genes, chromosomes & cancer Medium 14695992
2006 CHCHD7-PLAG1 is a recurrent gene fusion in pleomorphic adenomas generated by a cryptic intrachromosomal 8q rearrangement, where CHCHD7 (located head-to-head ~500 bp from PLAG1) provides its promoter to drive PLAG1 expression by promoter swapping. PLAG1 protein is overexpressed in epithelial, myoepithelial, and mesenchymal-like tumor cells in these tumors. Cytogenetics, molecular analysis, Northern blot, Western blot, immunohistochemistry, FISH on nuclear chromatin fibers Genes, chromosomes & cancer High 16736500
2006 PLAG1 activates transcription of mouse (but not human) beta-catenin; four PLAG1 consensus binding sites are present in the mouse beta-catenin promoter but not in human. In PLAG1 transgenic mouse tumors, beta-catenin and downstream Wnt target c-myc are upregulated at the transcriptional level. Cotransfection reporter assay in 3T3 cells, promoter sequence analysis, immunohistochemistry International journal of cancer Medium 16108035
2008 Inactivation of Igf2 in PLAG1-transgenic mice (P1-MCre) significantly delays salivary gland tumor development but does not fully abrogate it; Wnt signaling genes (Wnt6, Cyclin D1, beta-catenin), H19, Dlk1, Gtl2, Igfbp2, and Igfbp3 are upregulated in the Igf2-inactivated PLAG1 tumors, indicating both IGF and Wnt signaling contribute to PLAG1-induced tumorigenesis. Genetic epistasis in conditional transgenic mice (Igf2 inactivation on PLAG1-OE background), tumor latency measurement, gene expression analysis International journal of oncology High 18425330
2007 FGFR1-PLAG1 fusion genes are generated by ring chromosome formation from chromosome 8; the 5' part of FGFR1 (8p12) is linked to the PLAG1 coding sequence (8q12.1), providing an active promoter to drive PLAG1 expression. SKY, FISH, high-resolution oligonucleotide array-CGH, molecular analysis Oncogene Medium 18059337
2009 PLAG1 protein expression is elevated in CLL cells compared to normal B cells due to translational derepression, caused by epigenetic silencing (methylation) of miR-181a, miR-181b, miR-107, and miR-424. Luciferase reporter assays with site-directed mutagenesis of the PLAG1 3'UTR confirmed direct regulation of PLAG1 by these miRNAs. PLAG1 mRNA levels were not affected, demonstrating post-transcriptional regulation. miRNA expression profiling, luciferase reporter assays with site-directed mutagenesis of 3'UTR binding sites, Western blot, methylation analysis of miRNA promoters Blood High 19692702
2012 PLAG1 binding to the IGF2 P3 promoter is cell type-specific; ChIP shows PLAG1 binding in Hep3B but not JEG-3 cells at the endogenous locus. The H19 chromatin insulator modulates PLAG1 responsiveness in a cell type-dependent manner. PLAG1 induction partially overrides insulator function in reporter systems but does not consistently activate the endogenous IGF2 gene in JEG-3 cells. Chromatin immunoprecipitation (ChIP), GFP reporter/insulator assay, FACS analysis of stable inducible PLAG1 cell clones International journal of oncology Medium 23023303
2017 PLAG1 upregulates GDH1 (glutamate dehydrogenase 1) expression upon cell detachment, providing anti-anoikis signals in LKB1-deficient lung cancer. The GDH1 product alpha-KG activates CamKK2 by enhancing its substrate AMPK binding, promoting energy production conferring anoikis resistance. This establishes a PLAG1-GDH1-alpha-KG-CamKK2-AMPK axis. Genetic knockdown/overexpression, biochemical assays, patient-derived xenograft model, co-immunoprecipitation Molecular cell High 29249655
2017 Functional experiments demonstrate that HMGA2 regulates IGF2 expression through PLAG1, establishing a HMGA2-PLAG1-IGF2 regulatory pathway. Loss-of-function mutations in PLAG1 in humans cause Silver-Russell syndrome with fetal growth restriction. HMGA2 also regulates IGF2 in a PLAG1-independent manner. Whole-exome sequencing, targeted sequencing, functional experiments linking genes in the pathway Genetics in medicine High 28796236
2014 HMGA2 overexpression in MCF-7 cells induces increased PLAG1 mRNA expression within 24–48 hours, and stimulation of HMGA2 by FGF1 in adipose-derived stem cells simultaneously increases PLAG1 mRNA. In leiomyomas with HMGA2 overexpression but no chromosome 8 abnormalities, PLAG1 is consistently activated, suggesting HMGA2 is an upstream transcriptional activator of PLAG1. Transient transfection of HMGA2 in MCF-7 cells, FGF1 stimulation assay, quantitative RT-PCR PloS one Medium 24516594
2017 PLAG1 deficiency in male mice results in significantly reduced daily sperm production, reduced sperm motility, and sloughing of the germinal epithelium. PLAG1 is expressed in germ cells and Sertoli cells. Genes involved in spermatogenesis and Hsd17b3 (androgen biosynthesis) are downregulated in Plag1 knockout testes. Plag1 knockout mouse analysis, X-gal staining for localization, RNA-seq, testicular histology, sperm motility assays Scientific reports High 28706261
2018 PLAG1 and USF2 co-occupy the MSI2 promoter in human hematopoietic stem and progenitor cells (HSPCs) and cooperate to transactivate endogenous MSI2. Coincident overexpression of PLAG1 and USF2 in cord blood progenitors enhances MSI2 transcription and expands CD34+ cells in vitro. ChIP-seq confirms co-binding of PLAG1 and USF2 at the MSI2 promoter and other HSPC regulatory loci. ChIP-seq, luciferase reporter assays, PLAG1/USF2 overexpression in cord blood cells, FACS for CD34+ expansion Stem cell reports High 29641991
2018 PLAG1 is a microRNA target gene derepressed by mutations in microRNA biogenesis machinery in Wilms tumors. PLAG1 overexpression accelerates Wilms tumor cell growth in vitro and induces neoplastic growth in the developing mouse kidney in vivo by transactivating IGF2 and driving mTORC1 signaling. In vitro cell growth assays, in vivo mouse kidney injection model, luciferase reporter for IGF2 transactivation, pathway analysis Genes & development High 30026293
2016 PLAG1 as a transcription factor reinforces BCL2 promoter activity, upregulating BCL2 mRNA; knockdown of PLAG1 reduces BCL2 expression and sensitizes AML cells to TRAIL-induced apoptosis and proliferation inhibition. Restoration of BCL2 eliminates the sensitizing effects of PLAG1 knockdown. BCL2 promoter luciferase reporter assay, PLAG1 siRNA knockdown, apoptosis and proliferation assays, BCL2 restoration rescue experiment Oncotarget Medium 27013583
2022 PLAG1 is essential for long-term human HSC function and promotes HSC self-renewal by dampening protein synthesis. Genome-wide ChIP occupancy and gene expression analysis show PLAG1 restrains translation via upregulating 4EBP1 and translation-targeting miR-127, independently of stress response signaling. The advantages conferred by PLAG1 are attenuated by c-MYC overexpression. Genome-wide chromatin occupancy (ChIP-seq), RNA-seq, functional HSC assays, in vitro protein synthesis measurement, genetic epistasis with c-MYC Blood High 35639948
2020 PLAG1 promotes proliferation and inhibits apoptosis in bovine primary myoblasts by upregulating phosphorylated PI3K/Akt, Cyclin D1, and CDK2 (via ChIP-seq evidence) and upregulating Bcl-2/Bcl-xL while inhibiting p21/p27. PLAG1 is a direct target of miR-1, which negatively regulates PLAG1 expression. CCK-8 assay, EdU proliferation assay, ChIP-seq, flow cytometry, Western blot, dual-luciferase assay for miR-1 targeting Journal of animal science Medium 35325183
2020 PLAG1 silencing in ovarian cancer cells decreases expression of IGF2, IGF1 receptor, and IRS1, and inhibits cell proliferation, migration, invasion, and cisplatin resistance in an IGF2-dependent manner. siRNA knockdown, pcDNA overexpression, cell proliferation/migration/invasion assays, Western blot International journal of molecular medicine Medium 31922228
2018 PLAG1 promotes proliferation and survival of rhabdomyosarcoma cells by inducing IGF2 expression and activating AKT and MAPK pathways. IGF2 partially rescues cell death triggered by PLAG1 knockdown. PLAG1 expression level correlates with sensitivity to IGF receptor inhibitor BMS754807. PLAG1 knockdown and ectopic overexpression, xenograft model, pathway activation assays (AKT/MAPK), IGF2 rescue experiment Molecular cancer research Medium 31757836
2024 PLAG1 confers resistance to sorafenib-induced ferroptosis in HCC by transcriptionally driving expression of GPX4 (glutathione peroxidase 4), thereby reducing lipid peroxidation. Sorafenib decreases PLAG1 at the transcriptional level through its upstream lncRNA PVT1. ChIP assay confirmed PLAG1 binding to the GPX4 promoter; PLAG1 and GPX4 protein levels are positively correlated in HCC patients. ChIP assay, luciferase reporter assay, ubiquitination assay, RNA immunoprecipitation (RIP) assay, CRISPR screening, tissue microarrays Journal of experimental & clinical cancer research Medium 38745179
2018 In Wilms tumors, PLAG1 promoter occupancy by ChIP-seq analysis and MSI2 co-regulation experiments establish that PLAG1 directly activates MSI2 transcription in HSPCs alongside USF2. ChIP-seq Stem cell reports Medium 29641991
2018 Plag1 mutant neocortical progenitors proliferate less and produce more neurons at E12.5, while Plag1 gain-of-function reduces neurogenesis and increases BrdU uptake (enhanced proliferation). Plag1 and Plagl2 double-mutants are embryonic lethal, indicating at least one copy of either gene is required for embryonic survival. Single and double mutant mouse analysis, BrdU labeling, neurogenesis quantification in neocortex Biology open Medium 30361413
2008 Furin (proprotein convertase) facilitates PLAG1-induced salivary gland tumorigenesis; genetic ablation of fur with PLAG1 overexpression significantly delays tumor onset, and fur inactivation alone causes smaller but histologically normal salivary glands. MMTV-Cre genetic epistasis in mice (fur KO on PLAG1 transgenic background), histopathology, tumor latency measurement International journal of oncology Medium 18425334
2020 PLAG1 acts as a transcriptional activator of PLIN1 (perilipin 1) in bovine adipocytes. EMSA and siRNA interference confirmed PLAG1 binding to its consensus site in the PLIN1 core promoter (-209/-17 bp), and PLAG1 knockdown reduced PLIN1-driven luciferase activity and impaired lipid metabolism in adipocytes. Promoter cloning and luciferase assay, EMSA, siRNA knockdown, mutational analysis of promoter fragments Genomics Medium 31981700

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 269 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 187 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 130 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 115 23630011
2004 Plag1 and Plagl2 are oncogenes that induce acute myeloid leukemia in cooperation with Cbfb-MYH11. Blood 112 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 107 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
2004 Amplification and overexpression of the IGF2 regulator PLAG1 in hepatoblastoma. Genes, chromosomes & cancer 82 14695992
2006 CHCHD7-PLAG1 and TCEA1-PLAG1 gene fusions resulting from cryptic, intrachromosomal 8q rearrangements in pleomorphic salivary gland adenomas. Genes, chromosomes & cancer 81 16736500
2015 Emerging role of PLAG1 as a regulator of growth and reproduction. The Journal of endocrinology 80 26577933
2017 PLAG1 immunohistochemistry is a sensitive marker for pleomorphic adenoma: a comparative study with PLAG1 genetic abnormalities. Histopathology 76 28796899
2012 PLAG1 alteration in carcinoma ex pleomorphic adenoma: immunohistochemical and fluorescence in situ hybridization studies of 22 cases. Head and neck pathology 75 22485045
2019 Novel PLAG1 Gene Rearrangement Distinguishes a Subset of Uterine Myxoid Leiomyosarcoma From Other Uterine Myxoid Mesenchymal Tumors. The American journal of surgical pathology 73 30489320
2004 Targeted disruption of the murine Plag1 proto-oncogene causes growth retardation and reduced fertility. Development, growth & differentiation 73 15606491
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 70 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 64 33027073
2013 miR-141 contributes to fetal growth restriction by regulating PLAG1 expression. PloS one 60 23554918
2007 High-resolution array CGH analysis of salivary gland tumors reveals fusion and amplification of the FGFR1 and PLAG1 genes in ring chromosomes. Oncogene 59 18059337
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
2000 Evidence of involvement of the PLAG1 gene in lipoblastomas. International journal of oncology 56 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 47 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 46 33097826
2020 NDRG1-PLAG1 and TRPS1-PLAG1 Fusion Genes in Chondroid Syringoma. Cancer genomics & proteomics 44 32345665
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
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 37 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
2005 Sumoylation and acetylation play opposite roles in the transactivation of PLAG1 and PLAGL2. The Journal of biological chemistry 32 16207715
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 30 36624091
2020 Pediatric fibromyxoid soft tissue tumor with PLAG1 fusion: A novel entity? Genes, chromosomes & cancer 30 33300192
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
2014 Correlated expression of HMGA2 and PLAG1 in thyroid tumors, uterine leiomyomas and experimental models. PloS one 29 24516594
2021 Methylation and Expression of FTO and PLAG1 Genes in Childhood Obesity: Insight into Anthropometric Parameters and Glucose-Lipid Metabolism. Nutrients 28 34063412
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
2020 Differential Expression of PLAG1 in Apocrine and Eccrine Cutaneous Mixed Tumors: Evidence for Distinct Molecular Pathogenesis. The American Journal of dermatopathology 27 30839344
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
2019 Identification of a novel BOC-PLAG1 fusion gene in a case of lipoblastoma. Biochemical and biophysical research communications 26 30857637
2019 Metastasizing Pleomorphic Adenoma: Recurrent PLAG1/HMGA2 Rearrangements and Identification of a Novel HMGA2-TMTC2 Fusion. The American journal of surgical pathology 25 31094927
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 Assessment of HMGA2 and PLAG1 rearrangements in breast adenomyoepitheliomas. NPJ breast cancer 24 30675516
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
2022 PLAG1 dampens protein synthesis to promote human hematopoietic stem cell self-renewal. Blood 23 35639948
2021 PLAG1-rearrangment in a uterine leiomyosarcoma with myxoid stroma and heterologous differentiation. Genes, chromosomes & cancer 23 34184333
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
2018 PLAG1, SOX10, and Myb Expression in Benign and Malignant Salivary Gland Neoplasms. Journal of pathology and translational medicine 22 30424592
2018 Plag1 and Plagl2 have overlapping and distinct functions in telencephalic development. Biology open 21 30361413
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
2020 Activation of PLAG1 and HMGA2 by gene fusions involving the transcriptional regulator gene NFIB. Genes, chromosomes & cancer 20 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
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 18 35822448
2021 Novel morphologic findings in PLAG1-rearranged soft tissue tumors. Genes, chromosomes & cancer 18 33893698
2021 Some pleomorphic adenomas of the breast share PLAG1 rearrangements with the analogous tumour of the salivary glands. Histopathology 18 34292619
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
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
2024 PLAG1-Rearranged Uterine Sarcomas: A Study of 11 Cases Showing a Wide Phenotypical Spectrum Not Limited to Myxoid Leiomyosarcoma-Like Morphology. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 14 38942115
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
2022 Pleomorphic adenoma gene 1 (PLAG1) promotes proliferation and inhibits apoptosis of bovine primary myoblasts through the PI3K-Akt signaling pathway. Journal of animal science 12 35325183
2019 The PLAG1 mRNA expression analysis among genetic variants and relevance to growth traits in Chinese cattle. Animal biotechnology 12 31253059

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