Affinage

PRDM2

PR domain zinc finger protein 2 · UniProt Q13029

Length
1718 aa
Mass
188.9 kDa
Annotated
2026-06-10
100 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PRDM2 (RIZ) is a nuclear, sequence-specific zinc-finger protein that functions as a histone H3 lysine 9 methyltransferase and transcriptional repressor, and acts as a tumor suppressor whose loss promotes proliferation and malignant transformation (PMID:11544182, PMID:29228717). The gene encodes two products through an internal promoter: RIZ1, which contains the catalytic N-terminal PR/SET domain, and RIZ2, which lacks it; RIZ1 is selectively lost in cancers while RIZ2 is retained, and the PR domain modulates repressor potency (PMID:9006946, PMID:9334209, PMID:9766644). The PR domain adopts a SET-like fold and possesses intrinsic methyltransferase activity, preferentially depositing repressive H3K9me1/2 marks; cancer-associated missense mutations cluster in this domain and reduce catalytic activity (PMID:15964548, PMID:18082620, PMID:24423864, PMID:25934289). RIZ1 binds GC-rich/Sp1 elements through its first three zinc fingers and is recruited to target promoters including IGF-1 and Akt3, where it increases H3K9 methylation and dampens downstream ERK and AKT signaling (PMID:9334209, PMID:16953217, PMID:29367689). Full tumor suppressor function requires both the PR/SET methyltransferase domain and a C-terminal domain that directly binds PR-Set7/KMT5a, which is also necessary for nuclear localization and for maintaining the H4K20me1–H3K9me1 trans-tail histone code; truncating frameshift mutations that prevent this interaction abolish tumor suppression (PMID:24423864). PRDM2 also engages the chromatin machinery more broadly, interacting with the PRC2 component EZH2 to control bivalent chromatin and reversible quiescence at cell-cycle gene loci such as CCNA2 (PMID:26040698). Beyond chromatin, RIZ1 binds the retinoblastoma protein via an intrinsically disordered acidic region carrying an IRCDE/LXCXE-like motif and can form a ternary complex with Rb and E2F1 (PMID:7538672, PMID:9223517, PMID:25640033), and it forms a ligand-dependent complex with estrogen receptor α acting as a co-activator (PMID:10706618, PMID:11544182). PRDM2 is itself epigenetically silenced in tumors through DNA promoter methylation and H3K9 trimethylation, and its in vivo loss drives lymphoma and a broad tumor spectrum (PMID:11544182, PMID:20675009, PMID:29228717). Functionally, PRDM2 controls cellular quiescence, differentiation, and epithelial–mesenchymal transition, and in the nervous system H3K9me1-dependent PRDM2 activity in the prefrontal cortex regulates alcohol-dependence behaviors (PMID:26040698, PMID:27573876, PMID:29228717).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1995 Medium

    Identifying PRDM2/RIZ as a direct Rb-binding nuclear protein placed it within the retinoblastoma tumor suppressor network and motivated study of its growth-control role.

    Evidence cDNA library screening for Rb-binding proteins and binding assays

    PMID:7538672

    Open questions at the time
    • Functional consequence of the Rb interaction not established
    • Binding interface not yet mapped
  2. 1997 High

    Establishing that an internal promoter generates PR-domain-containing RIZ1 and PR-domain-lacking RIZ2 defined the yin-yang isoform structure central to PRDM2 biology.

    Evidence Immunoprecipitation, immunoblot, RNase protection, immunofluorescence after transfection

    PMID:9006946

    Open questions at the time
    • Catalytic role of the PR domain not yet demonstrated
    • Functional divergence of isoforms not yet established
  3. 1997 High

    Mapping DNA-binding to the first three zinc fingers and a central repressor domain, with stronger repression by RIZ1, showed the protein is a sequence-specific transcriptional repressor whose PR domain modulates activity.

    Evidence Recombinant DNA-binding assays, GAL4 reporter domain mapping, transfection; plus in vitro Rb-pocket ternary complex with E2F1

    PMID:9223517 PMID:9334209

    Open questions at the time
    • In vivo target genes not identified
    • Link between DNA binding and histone modification not yet made
  4. 1998 High

    Demonstrating that RIZ1 (but not RIZ2) induces G2/M arrest and apoptosis and is selectively lost in breast cancer established isoform-specific tumor suppression.

    Evidence Adenoviral forced expression, flow cytometry, viability assays in breast cancer cells

    PMID:9766644

    Open questions at the time
    • Molecular basis of growth arrest not defined
    • Mechanism of selective RIZ1 loss not addressed
  5. 1999 High

    Showing a ligand-dependent RIZ–ERα complex and estrogen-responsive promoter targeting expanded PRDM2's role into nuclear hormone receptor signaling.

    Evidence Co-IP, domain mapping, CAST/EMSA, reporter assays in MCF-7 and rat endometrium

    PMID:10544042 PMID:10706618

    Open questions at the time
    • Whether co-activation involves methyltransferase activity unresolved
    • Direct vs indirect ERα contact not fully defined
  6. 2001 High

    Knockout of the RIZ1 locus causing lymphoma and tumors, with PR-domain mutations clustering in human cancers, provided genetic proof of tumor suppression centered on the methyltransferase domain.

    Evidence Targeted mouse knockout, human tumor mutation sequencing, ERα transactivation assays; plus differentiation induction in HL60 cells

    PMID:11544182 PMID:11591891

    Open questions at the time
    • Enzymatic activity of the PR domain not yet directly measured
    • Direct substrate of the PR domain not yet defined
  7. 2007 High

    Solving the PR-domain structure as a SET-like fold that binds the H3 N-terminal peptide established the molecular basis for PRDM2 acting as an H3K9 methyltransferase.

    Evidence Solution NMR structure, SAH and H3 peptide binding assays; earlier DXMS structural mapping

    PMID:15964548 PMID:18082620

    Open questions at the time
    • Catalytic mechanism and methyl-donor handling unclear (no SAH affinity detected)
    • Specific H3K9 lysine targeting not confirmed structurally
  8. 2006 High

    ChIP demonstrating RIZ1 occupancy and H3K9 methylation at the IGF-1 promoter with reduced downstream ERK/AKT signaling connected chromatin repression to a defined oncogenic signaling output.

    Evidence ChIP, microarray, forced expression, signaling Western blots in CML blast crisis cells

    PMID:16953217

    Open questions at the time
    • Genome-wide target spectrum not yet defined
    • Direct vs indirect signaling effects not separated
  9. 2014 High

    Identifying direct KMT5a/PR-Set7 binding to the RIZ1 C-terminus as required for nuclear localization, the H4K20me1–H3K9me1 trans-tail code, and tumor suppression unified catalysis, localization, and cancer-associated truncations into one mechanistic model.

    Evidence Co-IP/pulldown, in vitro H3K9 methyltransferase assay, imaging, domain mutagenesis with phenotypic readout

    PMID:24423864

    Open questions at the time
    • Stoichiometry and structure of the RIZ1–PR-Set7 complex unknown
    • How the trans-tail code is read by downstream factors unresolved
  10. 2015 High

    Defining the disordered acidic region with an IRCDE motif as the submicromolar Rb-pocket binding element clarified the structural basis of the long-known RIZ1–Rb interaction.

    Evidence NMR, ITC, fluorescence anisotropy with recombinant proteins

    PMID:25640033

    Open questions at the time
    • Cellular consequence of competing with E2F for Rb not established
    • Regulation of the interaction in vivo unknown
  11. 2015 High

    Showing PRDM2 enrichment in quiescent muscle stem cells, genome-wide promoter occupancy with H3K9me2, and interaction with EZH2 positioned PRDM2 as an upstream regulator of bivalent chromatin and reversible quiescence.

    Evidence ChIP-seq, ChIP-qPCR, siRNA, Co-IP, flow cytometry, live imaging; plus isolated PR-domain transduction with intrinsic HMT activity

    PMID:25934289 PMID:26040698

    Open questions at the time
    • Mechanism of PRDM2-directed EZH2 recruitment not defined
    • Relationship between H3K9me2 and PRC2-deposited marks at shared loci unresolved
  12. 2016 High

    In vivo viral knockdown linking PRDM2/H3K9me1 loss in the prefrontal cortex to compulsive alcohol drinking extended PRDM2's epigenetic function to neurobehavioral regulation.

    Evidence Viral-vector knockdown, ChIP-seq for H3K9me1, behavioral assays in rats

    PMID:27573876

    Open questions at the time
    • Specific synaptic target genes mediating behavior not pinpointed
    • Upstream signals lowering PRDM2 in dependence unclear
  13. 2017 High

    Isogenic correction of a somatic PRDM2 frameshift restoring global H3K9me2 and reversing EMT/tumor phenotypes provided causal evidence that catalytic loss drives malignancy through EMT regulation.

    Evidence CRISPR isogenic correction, global histone methylation analysis, migration/anchorage-independent growth, xenograft, GSEA in colorectal cancer; plus HBx/DNMT1-mediated promoter silencing

    PMID:28339081 PMID:29228717

    Open questions at the time
    • Direct EMT target genes bound by PRDM2 not mapped
    • Whether VIM is a direct or indirect target unresolved
  14. 2024 Medium

    Accumulating gain/loss-of-function studies define recurrent PRDM2 regulatory axes (Akt3 repression, c-Myc/UBE2C and p53 modulation, D2DR upregulation) but their direct chromatin basis is incompletely resolved.

    Evidence Overexpression/knockdown with reporter, ChIP, and signaling readouts across prolactinoma, somatotroph, meningioma, and leukemia cells

    PMID:20417662 PMID:20594067 PMID:25884948 PMID:28560012 PMID:29367689 PMID:32044406

    Open questions at the time
    • Direct vs indirect regulation of c-Myc/p53 not separated by chromatin occupancy
    • Several axes rest on single-lab overexpression studies

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PRDM2 activity is post-translationally controlled and how its catalytic and scaffolding functions are integrated to direct target selectivity remain open.
  • Phosphorylation sites Ser643/Ser421 and ATR regulation not experimentally validated
  • No structure of full-length PRDM2 or its multiprotein complexes
  • Rules governing genome-wide target promoter selection unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0140110 transcription regulator activity 4 GO:0003677 DNA binding 3 GO:0042393 histone binding 2
Localization
GO:0005634 nucleus 4 GO:0000228 nuclear chromosome 3
Pathway
R-HSA-4839726 Chromatin organization 4 R-HSA-1640170 Cell Cycle 3 R-HSA-1643685 Disease 2 R-HSA-74160 Gene expression (Transcription) 2
Partners
E2F1ESR1ESR2EZH2KMT5ARB1

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 PRDM2/RIZ is a 250-kDa nuclear protein that directly binds the retinoblastoma protein (Rb) via an Rb-binding motif; the interaction was identified by cDNA library screening for Rb-binding proteins. cDNA library screening, binding assay Proceedings of the National Academy of Sciences of the United States of America Medium 7538672
1997 The RIZ gene produces two protein products via an internal promoter: RIZ1 (280 kDa, contains the PR domain) and RIZ2 (250 kDa, lacks the PR domain). Both are nuclear proteins as determined by immunofluorescence after transfection. Immunoprecipitation, immunoblot, RNase protection assay, immunofluorescence, transfection The Journal of biological chemistry High 9006946
1997 RIZ1 and RIZ2 bind GC-rich/Sp1-binding elements via the first three zinc finger motifs and repress transcription; a repressor domain was mapped to the central region of the protein. RIZ1 more potently represses SV40 promoter than RIZ2, indicating the PR domain modulates repressor function. Recombinant protein DNA-binding assay, GAL4 fusion transcription reporter assay, transfection The Journal of biological chemistry High 9334209
1997 The acidic region of RIZ (containing IRCDE/CR2-like motif) specifically interacts with the E1A-binding domain of Rb, can form a ternary complex with Rb and E2F1, but does not bind the Rb family members p107 or p130 in vitro. In vitro binding assay, peptide competition, ternary complex formation Journal of virology Medium 9223517
1998 Forced RIZ1 expression in breast cancer cells causes G2/M cell cycle arrest and/or apoptosis; RIZ2 is normally expressed in all breast cancer cases whereas RIZ1 is specifically lost, indicating selective tumor suppressive activity of the RIZ1 isoform. Adenoviral forced expression, flow cytometry cell cycle analysis, cell viability assay Cancer research High 9766644
1999 RIZ/PRDM2 protein co-immunoprecipitates with estrogen receptor (ERα) in cell extracts from cultured cells and target tissues in a ligand-dependent manner; mapping identified shared interaction regions. Estradiol induces redistribution of RIZ protein within the nucleus and cytoplasm in vitro and in vivo in rat endometrium. Co-immunoprecipitation, interaction domain mapping, immunolocalization in cultured cells and rat tissue Proceedings of the National Academy of Sciences of the United States of America High 10706618
1999 RIZ protein binds to a TTGGC DNA motif identified by CAST selection and co-immunoprecipitates with estrogen receptor from MCF-7 cell extracts; RIZ confers estrogen inducibility to a promoter containing this motif in transfection experiments. CAST (cyclic amplification and selection of target), EMSA, Co-IP, transfection reporter assay Biochemical and biophysical research communications Medium 10544042
2001 Targeted inactivation of the RIZ1 locus (leaving RIZ2 intact) in mice causes a high incidence of diffuse large B-cell lymphomas and broad spectrum of tumors; missense mutations in human tumors cluster in the MTase (PR) domain and abolish RIZ1's capacity to enhance estrogen receptor transactivation. Targeted mouse knockout, tumor analysis, human tumor mutation sequencing, transcription activation assay Genes & development High 11544182
2001 RIZ1 expression is selectively induced during retinoic acid-, TPA-, or vitamin D3-driven myeloid differentiation of HL60 cells with redistribution within the nucleus; forced RIZ1 expression arrests HL60 growth and causes cell death. RT-PCR, RNase protection assay, immunocytochemistry, adenoviral forced expression, cell viability assay Molecular medicine Medium 11591891
2004 The RIZ1 P704 deletion polymorphism shows impaired co-activation of ERα in a ligand- and dose-dependent manner compared to the P704+ allele, establishing this region as functionally important for RIZ1's role as an ERα co-activator. In vitro transcription co-activation assay (reporter gene), comparison of polymorphic variants The Journal of clinical endocrinology and metabolism Medium 15579774
2005 The PR domain of RIZ1 is structurally homologous to SET domains with a pseudo-knot at the C-terminus and flexible segments at the carboxyl terminus involved in H3K9 methylation; cancer-associated missense mutations map to the PR domain and reduce methyltransferase activity. Deuterium exchange mass spectrometry, domain mapping, selective deletion mutagenesis, crystallization Biochemical and biophysical research communications Medium 15964548
2006 RIZ1 (PRDM2) associates with the promoter region of IGF-1 and increases histone H3 lysine 9 methylation at that promoter; forced RIZ1 expression in CML blast crisis cell lines decreases IGF-1 receptor activation and downstream ERK1/2 and AKT signaling. Chromatin immunoprecipitation (ChIP), cDNA microarray, forced expression, Western blotting for signaling components, IGF-1 blocking antibody Oncogene High 16953217
2007 The solution NMR structure of the RIZ1 PR domain reveals a typical SET fold including a C-terminal pseudo-knot; the domain does not have detectable affinity for the methyl donor by-product S-adenosyl-L-homocysteine (SAH) but interacts with a synthetic peptide comprising residues 1–20 of histone H3. NMR structure determination, SAH binding assay, histone H3 peptide binding Biochemical and biophysical research communications High 18082620
2008 RIZ1 is required for the cancer-preventive benefit of a methyl-balanced diet in mice; methyl-balanced diet upregulates RIZ1 expression, and higher RIZ1 activity correlates with increased H3K9 methylation at RIZ1 target gene promoters as shown by ChIP. Mouse dietary experiment (RIZ1 knockout vs. wild type), microarray gene expression, ChIP, quantitative RT-PCR PloS one Medium 18852888
2010 RIZ1 epigenetic silencing in hepatocellular carcinoma involves both DNA promoter methylation and H3K9 trimethylation; 5-Aza-dC promotes conversion of H3K9me3 to H3K9ac at the RIZ1 promoter preceding re-expression; HDAC1 (but not HDAC3) is downregulated by 5-Aza-dC/TSA treatment. Chromatin immunoprecipitation (ChIP), methylation-specific PCR, RT-PCR, immunohistochemistry, demethylating/HDAC inhibitor treatment Journal of hepatology Medium 20675009
2010 RIZ1 expression is induced by RANKL in macrophage-like cells and is required for osteoclast formation; RIZ1 siRNA knockdown reduces NFATc1 expression and impairs TRAP-positive multinucleated osteoclast formation. siRNA knockdown, RANKL stimulation assay, TRAP staining, Western blotting for NFATc1 Immunology letters Medium 20417662
2010 RIZ1 expression induced by TNF-α in monocytic leukemia cells is dependent on NF-κB and AKT signaling; RIZ1 in turn augments p53 expression, and RIZ1 silencing prevents p53 induction, resulting in enhanced proliferation. Pathway inhibition, siRNA knockdown, Western blotting, proliferation assay Cancer investigation Medium 20594067
2012 An estrogen-responsive element (ERE) within the RIZ promoter 2 (driving RIZ2 expression) is regulated in a ligand-specific manner by ERα through both its AF1 and AF2 domains; association of topoisomerase IIβ with this promoter confirms transcriptional activation by estrogen, with cyclical H3K9 methylation patterns comparable to other estrogen-regulated promoters. Promoter reporter assay, ChIP for ERα and histone modifications, topoisomerase IIβ ChIP, transfection with ERα domain mutants Journal of cellular physiology Medium 21503890
2014 PR-Set7/KMT5a directly and specifically binds the C-terminus of Riz1/PRDM2; the PR/SET domain of Riz1 preferentially monomethylates H3K9; the PR-Set7-binding domain of Riz1 is required for its nuclear localization and for maintenance of the H4K20me1-H3K9me1 trans-tail histone code. Cancer-associated frameshift mutations truncating Riz1 and preventing PR-Set7 binding abolish tumor suppression; both the methyltransferase domain and PR-Set7-binding domain are required for tumor suppressor function. Direct binding assay (Co-IP, pulldown), H3K9 methyltransferase in vitro assay, nuclear localization by imaging, tumor suppression assay (proliferation/apoptosis), histone modification analysis Nucleic acids research High 24423864
2015 PRDM2/RIZ is enriched in quiescent muscle stem cells and controls reversible quiescence in cultured myoblasts; PRDM2 associates with >4400 promoters in G0 myoblasts (55% marked with H3K9me2), and knockdown alters histone methylation at Myogenin and CyclinA2 (CCNA2) promoters. PRDM2 protein interacts with PRC2 component EZH2 and regulates EZH2's association with a G0-specific bivalent chromatin domain at the CCNA2 locus, acting upstream of the PRC2 complex. ChIP-seq, ChIP-qPCR, siRNA knockdown, Co-IP (PRDM2-EZH2 interaction), flow cytometry, live imaging Nucleic acids research High 26040698
2015 The structural basis for RIZ1-Rb interaction was established: the acidic region (AR) of RIZ1 is intrinsically disordered and binds the pocket domain of Rb with submicromolar affinity; binding is mediated primarily by the short IRCDE motif within AR, analogous to the LXCXE motif of viral oncoproteins. NMR spectroscopy, isothermal titration calorimetry (ITC), fluorescence anisotropy, recombinant proteins Biochemistry High 25640033
2016 History of alcohol dependence persistently decreases Prdm2 expression in the rat dorsomedial prefrontal cortex, with decreased H3K9me1; viral-vector knockdown of Prdm2 in dmPFC phenocopies dependence-induced increases in alcohol self-administration and compulsive drinking. ChIP-seq shows genes involved in synaptic communication are regulated by H3K9me1 in dependent rats. Viral vector knockdown in vivo, ChIP-seq for H3K9me1, behavioral assays, qRT-PCR Molecular psychiatry High 27573876
2017 Somatic PRDM2 c.4467delA frameshift mutation in colorectal cancer cells reduces global H3K9 dimethylation; correction to wild-type by genome editing restores H3K9me2, reduces migration, anchorage-independent growth and tumor growth in vivo; gene set enrichment analysis identifies regulation of EMT (with VIM as most regulated gene) as a central aspect of PRDM2 tumor suppressive action. CRISPR/genome editing (isogenic cell line correction), global histone methylation analysis, migration assay, anchorage-independent growth, xenograft tumor model, gene set enrichment analysis Oncotarget High 29228717
2017 HBx (hepatitis B virus X protein) represses RIZ1 expression by upregulating DNMT1, which binds the RIZ1 promoter (shown by ChIP); this interaction is enhanced by HBx. Decreased miR-152 is involved in DNMT1 upregulation in HBx-transfected cells. ChIP, siRNA knockdown of DNMT1, HBx transfection, bisulfite sequencing, methylation-specific PCR Oncology reports Medium 28339081
2018 RIZ1 directly binds the Akt3 gene promoter and represses its transcription with concomitant increase in H3K9 methylation at the promoter; overexpression of RIZ1 reduces Akt3 protein and luciferase reporter activity from the Akt3 promoter. In vitro promoter binding with recombinant protein, ChIP, luciferase reporter assay, Western blotting Scientific reports Medium 29367689
2008 YY1 protein binds the RIZ1 promoter and positively regulates its transcription in osteosarcoma cells; YY1 presence reduces H3K9 dimethylation at the promoter as shown by ChIP. Silencing of YY1 decreases RIZ1 protein expression. ChIP, promoter reporter assay, YY1 siRNA knockdown, RT-PCR, Western blot Oncology research Medium 18488713
2015 PRDM2 overexpression upregulates dopamine receptor D2 (D2DR) expression and inhibits ERK1/2 phosphorylation in MMQ prolactinoma cells; PRDM2 shows a synergistic effect with bromocriptine in inhibiting prolactin secretion and cell viability. Overexpression in cell line, Western blot for ERK phosphorylation, RT-PCR for D2DR, cell viability assay BMC cancer Medium 25884948
2009 RIZ1 protein is localized to the nucleus in normal prostate epithelial cells; in cancer cells with higher Gleason score, RIZ1 shifts from nuclear to cytoplasmic localization. RIZ1 co-immunoprecipitates with both ERα and ERβ in estrogen-treated prostate epithelial cells. Immunohistochemistry, subcellular fractionation/localization, Co-IP with ERα and ERβ, RT-PCR Journal of cellular physiology Medium 19746436
2020 PRDM2 negatively regulates c-Myc expression in somatotroph adenoma GH3 cells; overexpression of PRDM2 induces G2/M arrest, apoptosis, and inhibits invasion, and elevates CDKN1A and CDKN1B levels. Combined with c-Myc inhibitor, PRDM2 further suppresses proliferation, establishing a functional PRDM2–c-Myc axis. Overexpression in GH3 cells, flow cytometry, transwell invasion assay, RT-PCR, Western blot, c-Myc inhibitor co-treatment Gene Medium 32044406
2017 RIZ1 negatively regulates UbcH10 (UBE2C) expression in a c-Myc-dependent manner in meningioma cells: RIZ1 overexpression decreases c-Myc which in turn reduces UbcH10, a c-Myc target gene, providing a RIZ1→c-Myc→UbcH10 regulatory axis. Overexpression, siRNA knockdown, Western blot, RT-PCR, reporter assay American journal of translational research Low 28560012
2015 The isolated N-terminal PR domain of RIZ1 possesses intrinsic histone methyltransferase activity and tumor-suppressive (growth-inhibitory) activity in meningioma cells; microarray analysis of PR-domain-treated cells identifies c-Myc and TXNIP as putative H3K9 methylation downstream targets. Recombinant TAT-RIZ1-PR protein transduction, histone methyltransferase activity assay, microarray, xenograft tumor model Biomaterials Medium 25934289
2015 RIZ1 knockdown in cholangiocarcinoma CCA cells (which show predominant nuclear localization of RIZ1) augments cell proliferation and migration, defining RIZ1 as a regulator of these processes in this cell type. siRNA knockdown, nuclear localization by microscopy, proliferation assay, migration assay Asian Pacific journal of cancer prevention Low 23098508
2025 PRDM2 phosphosites Ser643 and Ser421 are the predominant phosphorylation sites across large-scale phosphoproteomics datasets; ATR kinase is computationally predicted to phosphorylate these sites; co-regulated phosphosites are enriched in DNA damage response pathways. However, this is a computational/bioinformatic study and functional consequences of phosphorylation were not experimentally validated. Computational phosphoproteomics meta-analysis, expression co-regulation analysis, kinase prediction 3 Biotech Low 42179918

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Tumor formation and inactivation of RIZ1, an Rb-binding member of a nuclear protein-methyltransferase superfamily. Genes & development 165 11544182
1995 The retinoblastoma protein binds to RIZ, a zinc-finger protein that shares an epitope with the adenovirus E1A protein. Proceedings of the National Academy of Sciences of the United States of America 162 7538672
2001 Hypermethylation in human cancers of the RIZ1 tumor suppressor gene, a member of a histone/protein methyltransferase superfamily. Cancer research 150 11719434
2000 Candidate tumor suppressor RIZ is frequently involved in colorectal carcinogenesis. Proceedings of the National Academy of Sciences of the United States of America 147 10688904
1998 RIZ1, but not the alternative RIZ2 product of the same gene, is underexpressed in breast cancer, and forced RIZ1 expression causes G2-M cell cycle arrest and/or apoptosis. Cancer research 131 9766644
1997 The retinoblastoma interacting zinc finger gene RIZ produces a PR domain-lacking product through an internal promoter. The Journal of biological chemistry 90 9006946
1999 Decreased RIZ1 expression but not RIZ2 in hepatoma and suppression of hepatoma tumorigenicity by RIZ1. International journal of cancer 88 10508492
2000 Frequent frameshift mutations of RIZ in sporadic gastrointestinal and endometrial carcinomas with microsatellite instability. Cancer research 79 10987271
2000 Mapping of a minimal deleted region in human hepatocellular carcinoma to 1p36.13-p36.23 and mutational analysis of the RIZ (PRDM2) gene localized to the region. Genes, chromosomes & cancer 62 10862032
2001 Adenovirus expressing RIZ1 in tumor suppressor gene therapy of microsatellite-unstable colorectal cancers. Cancer research 56 11280725
2010 Epigenetic inactivation of the tumor suppressor gene RIZ1 in hepatocellular carcinoma involves both DNA methylation and histone modifications. Journal of hepatology 55 20675009
2004 Frequent epigenetic inactivation of RIZ1 by promoter hypermethylation in human gastric carcinoma. International journal of cancer 53 15069684
2006 RIZ1 repression is associated with insulin-like growth factor-1 signaling activation in chronic myeloid leukemia cell lines. Oncogene 48 16953217
2003 Biallelic inactivation of the RIZ1 gene in human gastric cancer. Oncogene 48 14534544
2001 RIZ, the retinoblastoma protein interacting zinc finger gene, is mutated in genetically unstable cancers of the pancreas, stomach, and colorectum. Genes, chromosomes & cancer 47 11135439
2000 The retinoblastoma-interacting zinc-finger protein RIZ is a downstream effector of estrogen action. Proceedings of the National Academy of Sciences of the United States of America 46 10706618
2005 Characterization of the PR domain of RIZ1 histone methyltransferase. Biochemical and biophysical research communications 45 15964548
2016 Dependence-induced increase of alcohol self-administration and compulsive drinking mediated by the histone methyltransferase PRDM2. Molecular psychiatry 43 27573876
2015 A fine balance: epigenetic control of cellular quiescence by the tumor suppressor PRDM2/RIZ at a bivalent domain in the cyclin a gene. Nucleic acids research 43 26040698
1996 Physical mapping of the retinoblastoma interacting zinc finger gene RIZ to D1S228 on chromosome 1p36. Genomics 43 8661032
1997 Transcriptional repression mediated by the PR domain zinc finger gene RIZ. The Journal of biological chemistry 42 9334209
2006 RIZ1 is epigenetically inactivated by promoter hypermethylation in thyroid carcinoma. Cancer 41 17103461
2002 Altered expression of retinoblastoma protein-interacting zinc finger gene, RIZ, in human leukaemia. British journal of haematology 41 12472571
2003 Intragenic allelic loss and promoter hypermethylation of the RIZ1 tumor suppressor gene in parathyroid tumors and pheochromocytomas. Surgery 37 14668725
1999 The retinoblastoma protein-interacting zinc finger gene RIZ in 1p36-linked cancers. Frontiers in bioscience : a journal and virtual library 37 10369808
2003 Detection of hypermethylated RIZ1 gene in primary tumor, mouth, and throat rinsing fluid, nasopharyngeal swab, and peripheral blood of nasopharyngeal carcinoma patient. Clinical cancer research : an official journal of the American Association for Cancer Research 35 12631603
2001 Preferential loss of a polymorphic RIZ allele in human hepatocellular carcinoma. British journal of cancer 32 11259086
2014 Methylation of PRDM2, PRDM5 and PRDM16 genes in lung cancer cells. International journal of clinical and experimental pathology 31 24966940
2012 Retinoblastoma protein-interacting zinc-finger gene 1 (RIZ1) dysregulation in human malignant meningiomas. Oncogene 31 22614009
2002 Frameshift mutations of RIZ, but no point mutations in RIZ1 exons in malignant melanomas with deletions in 1p36. Oncogene 31 12082534
2015 Lower PRDM2 expression is associated with dopamine-agonist resistance and tumor recurrence in prolactinomas. BMC cancer 30 25884948
2017 HBx represses RIZ1 expression by DNA methyltransferase 1 involvement in decreased miR-152 in hepatocellular carcinoma. Oncology reports 28 28339081
2015 RIZ1: a potential tumor suppressor in glioma. BMC cancer 28 26690953
2004 Clinicopathological significance of microsatellite instability and mutated RIZ in colorectal cancer. Annals of oncology : official journal of the European Society for Medical Oncology 27 14760116
2014 The PR-Set7 binding domain of Riz1 is required for the H4K20me1-H3K9me1 trans-tail 'histone code' and Riz1 tumor suppressor function. Nucleic acids research 26 24423864
1999 Identification of a DNA binding protein cooperating with estrogen receptor as RIZ (retinoblastoma interacting zinc finger protein). Biochemical and biophysical research communications 26 10544042
2007 DNA methylation of the RIZ1 gene is associated with nuclear accumulation of p53 in prostate cancer. Cancer science 25 17052263
2016 Critical Function of PRDM2 in the Neoplastic Growth of Testicular Germ Cell Tumors. Biology 24 27983647
2014 Effect of the downregulation of SMYD3 expression by RNAi on RIZ1 expression and proliferation of esophageal squamous cell carcinoma. Oncology reports 24 24993551
2018 Human PRDM2: Structure, function and pathophysiology. Biochimica et biophysica acta. Gene regulatory mechanisms 23 29883756
2008 Hyper-methylation of RIZ1 tumor suppressor gene is involved in the early tumorigenesis of hepatocellular carcinoma. Histology and histopathology 23 18712668
2012 Identification of a functional estrogen-responsive enhancer element in the promoter 2 of PRDM2 gene in breast cancer cell lines. Journal of cellular physiology 21 21503890
2005 Deletions and altered expression of the RIZ1 tumour suppressor gene in 1p36 in pheochromocytomas and abdominal paragangliomas. International journal of oncology 21 15809732
2008 Requirement of RIZ1 for cancer prevention by methyl-balanced diet. PloS one 20 18852888
2017 RIZ1 and histone methylation status in pituitary adenomas. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 19 28718376
2015 Detecting abnormal methylation of tumor suppressor genes GSTP1, P16, RIZ1, and RASSF1A in hepatocellular carcinoma and its clinical significance. Oncology letters 18 26622888
2009 RIZ1 is potential CML tumor suppressor that is down-regulated during disease progression. Journal of hematology & oncology 18 19602237
2009 Expression of RIZ1 protein (Retinoblastoma-interacting zinc-finger protein 1) in prostate cancer epithelial cells changes with cancer grade progression and is modulated in vitro by DHT and E2. Journal of cellular physiology 18 19746436
2002 The tumor suppressor gene RIZ in cancer gene therapy (review). Oncology reports 17 11748455
2017 Somatic PRDM2 c.4467delA mutations in colorectal cancers control histone methylation and tumor growth. Oncotarget 16 29228717
2012 Study on RIZ1 gene promoter methylation status in human esophageal squamous cell carcinoma. World journal of gastroenterology 16 22363126
2015 The transducible TAT-RIZ1-PR protein exerts histone methyltransferase activity and tumor-suppressive functions in human malignant meningiomas. Biomaterials 15 25934289
2010 Effects of triptolide on RIZ1 expression, proliferation, and apoptosis in multiple myeloma U266 cells. Acta pharmacologica Sinica 14 20523343
2010 Retinoblastoma protein-interacting zinc finger 1 (RIZ1) regulates the proliferation of monocytic leukemia cells via activation of p53. Cancer investigation 14 20594067
2004 A deletion polymorphism in the RIZ gene, a female sex steroid hormone receptor coactivator, exhibits decreased response to estrogen in vitro and associates with low bone mineral density in young Swedish women. The Journal of clinical endocrinology and metabolism 14 15579774
2011 Anticancer activity of the PR domain of tumor suppressor RIZ1. International journal of medical sciences 13 21369371
2007 Genetic polymorphisms in the Rb-binding zinc finger gene RIZ and the risk of lung cancer. Carcinogenesis 13 17693662
2004 The Zn-finger domain of RIZ protein promotes MCF-7 cell proliferation. Cancer letters 13 15488642
2021 Searching for a Putative Mechanism of RIZ2 Tumor-Promoting Function in Cancer Models. Frontiers in oncology 12 33585202
2015 Tumor suppressor RIZ1 in obesity and the PI3K/AKT/mTOR pathway. Obesity (Silver Spring, Md.) 12 26709097
2010 Aberrant methylation of the RIZ1 gene in myelodysplastic syndrome and acute myeloid leukemia. Leukemia research 12 20828818
2010 Suppression of RIZ in biologically unfavourable neuroblastomas. International journal of oncology 12 20878080
2007 The RIZ Pro704 insertion-deletion polymorphism, bone mineral density and fracture risk: the Rotterdam study. Bone 12 18037365
2007 Structural studies of the SET domain from RIZ1 tumor suppressor. Biochemical and biophysical research communications 12 18082620
2001 Differentiation of myeloid cell lines correlates with a selective expression of RIZ protein. Molecular medicine (Cambridge, Mass.) 12 11591891
2010 Retinoblastoma protein-interacting zinc finger 1 (RIZ1) participates in RANKL-induced osteoclast formation via regulation of NFATc1 expression. Immunology letters 11 20417662
2008 Silencing of YY1 downregulates RIZ1 promoter in human osteosarcoma. Oncology research 11 18488713
2005 Mutational study of the 1p located genes p18ink4c, Patched-2, RIZ1 and KIF1B in oligodendrogliomas. Oncology reports 11 15711769
2004 Detection of frameshift mutations of RIZ in gastric cancers with microsatellite instability. World journal of gastroenterology 11 15309726
1997 In vitro analysis of the E1A-homologous sequences of RIZ. Journal of virology 11 9223517
2020 The absence of PRDM2 involved the tumorigenesis of somatotroph adenomas through regulating c-Myc. Gene 10 32044406
2018 Combination of RIZ1 Overexpression and Radiotherapy Contributes to Apoptosis and DNA Damage of HeLa and SiHa Cervical Cancer Cells. Basic & clinical pharmacology & toxicology 10 29575614
2010 DNA methylation of the RIZ1 tumor suppressor gene plays an important role in the tumorigenesis of cervical cancer. European journal of medical research 10 20159667
2007 Decreased expression of RIZ1 and its clinicopathological significance in epithelial ovarian carcinoma: correlation with epigenetic inactivation by aberrant DNA methylation. Pathology international 10 17922684
2023 Exploring the putative role of PRDM1 and PRDM2 transcripts as mediators of T lymphocyte activation. Journal of translational medicine 9 36964555
2023 RIZ2 at the crossroad of the EGF/EGFR signaling in colorectal cancer. Journal of translational medicine 9 37853459
2020 Inactivation of lncRNA HOTAIRM1 caused by histone methyltransferase RIZ1 accelerated the proliferation and invasion of liver cancer. European review for medical and pharmacological sciences 9 32964965
2018 Repression of Akt3 gene transcription by the tumor suppressor RIZ1. Scientific reports 9 29367689
2017 RIZ1 is regulated by estrogen and suppresses tumor progression in endometrial cancer. Biochemical and biophysical research communications 9 28528974
2017 RIZ1 negatively regulates ubiquitin-conjugating enzyme E2C/UbcH10 via targeting c-Myc in meningioma. American journal of translational research 9 28560012
2012 Aberrant methylation and decreased expression of the RIZ1 gene are frequent in adult acute lymphoblastic leukemia of T-cell phenotype. Leukemia & lymphoma 8 22300346
2002 Nucleotide alteration of retinoblastoma protein-interacting zinc finger gene, RIZ, in human leukemia. The Tohoku journal of experimental medicine 8 12002276
2016 Synergism between RIZ1 gene therapy and paclitaxel in SiHa cervical cancer cells. Cancer gene therapy 7 27713401
2015 Aberrant Methylation of the 1p36 Tumor Suppressor Gene RIZ1 in Renal Cell Carcinoma. Asian Pacific journal of cancer prevention : APJCP 6 25987089
2010 Genetic and epigenetic alterations of RIZ1 and the correlation to clinicopathological parameters in liver fluke-related cholangiocarcinoma. Experimental and therapeutic medicine 6 22993552
2008 Cloning, expression, purification and crystallization of the PR domain of human retinoblastoma protein-binding zinc finger protein 1 (RIZ1). International journal of molecular sciences 6 19325838
2015 Structural and functional characterization of the acidic region from the RIZ tumor suppressor. Biochemistry 5 25640033
2024 Aberrant PRDM2 methylation as an early event in serrated lesions destined to evolve into microsatellite-instable colorectal cancers. The journal of pathology. Clinical research 4 38380944
2015 Identification of PRDM2 regulated genes in quiescent C2C12 myoblasts. Genomics data 4 26697392
2012 Contribution of RIZ1 to regulation of proliferation and migration of a liver fluke-related cholangiocarcinoma cell. Asian Pacific journal of cancer prevention : APJCP 4 23098508
2022 Therapeutic siRNA targeting the cancer cell stemness regulator PRDI-BF1 and RIZ domain zinc finger protein 14. Proceedings of the Japan Academy. Series B, Physical and biological sciences 3 35908955
2021 Effects of miR-362 in Regulating the Proliferation, Invasion and Apoptosis of Gastric Cancer by Inhibiting the Expression of Tumor-Promoting Factor PRDM2. Critical reviews in eukaryotic gene expression 3 33639051
2020 The predictive value of PRDM2 in solid tumor: a systematic review and meta-analysis. PeerJ 3 32391195
2016 Methylation Status of the RIZ1 Gene Promoter in Human Glioma Tissues and Cell Lines. Cellular and molecular neurobiology 3 27757741
2016 A deletion polymorphism in the RIZ gene is associated with increased progression of imatinib treated chronic myeloid leukemia patients. Leukemia & lymphoma 3 27830966
2025 siRNA-based therapeutic candidate targeting PRDM2 for inhibition of lung cancer progression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2 41273931
2025 Inhibition of AKT or mTOR molecules mitigates obesity-associated metabolic disorders in Riz1-/- mice with obesity. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 1 41151301
2023 Identification and Expressional Analysis of Putative PRDI-BF1 and RIZ Homology Domain-Containing Transcription Factors in Mulinia lateralis. Biology 1 37626944
2026 PRDM2 and DNA damage response: phosphoregulatory signaling insights. 3 Biotech 0 42179918
2025 PRDM2-The Key Research Targets for the Development of Diseases in Various Systems. Biomolecules 0 40867614

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