Affinage

RNF2

E3 ubiquitin-protein ligase RING2 · UniProt Q99496

Round 2 corrected
Length
336 aa
Mass
37.7 kDa
Annotated
2026-04-28
130 papers in source corpus 46 papers cited in narrative 46 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RNF2 (Ring1B/RING2) is the catalytic E3 ubiquitin ligase subunit of Polycomb Repressive Complex 1 (PRC1) and is essential for monoubiquitination of histone H2A at lysine 119, a modification central to Polycomb-mediated transcriptional silencing of developmental genes including Hox clusters and cell-cycle inhibitors such as Cdkn2a and Cdkn1a (PMID:15386022, PMID:12589020, PMID:19544461). Crystal structures show that RNF2 forms a RING-RING heterodimer with BMI1 (or other PCGF subunits), which allosterically stimulates its ligase activity; the E3–E2–nucleosome co-crystal reveals that substrate specificity arises from simultaneous contacts of Ring1B, UbcH5c, and BMI1 with nucleosomal DNA and the histone acidic patch (PMID:16710298, PMID:25355358). RNF2 stability is regulated by competing ubiquitin signals—activating self-ubiquitination via K6/K27 chains versus E6-AP-mediated K48-linked degradative ubiquitination, balanced by USP7 deubiquitination—and its genomic targeting is modulated by O-GlcNAcylation, MEK-dependent phosphorylation, and association with variant PRC1 complexes recruited by adaptors such as RYBP and KDM2B/FBXL10 (PMID:20351251, PMID:20800574, PMID:22325352, PMID:23395003, PMID:26100231). Beyond canonical H2AK119ub-dependent gene silencing, RNF2 catalyzes K33-linked ubiquitination of STAT1 to suppress interferon signaling, ubiquitinates non-histone substrates including SIK1, IRF4, and RASSF10 for proteasomal degradation, suppresses transcription-replication conflicts at common fragile sites, and cooperates with oncogenic transcription factors at active enhancers (PMID:29242538, PMID:27911266, PMID:34670117, PMID:32142505, PMID:33097530).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2002 High

    Establishing RNF2 as a core Polycomb complex subunit: Ring1B was identified as a component of human PRC1 that blocks chromatin remodeling and physically associates with other PcG proteins; hypomorphic mice displayed homeotic transformations with Hox gene derepression, placing Ring1B within the Polycomb gene-silencing paradigm.

    Evidence Biochemical purification of hPRC-H from HeLa cells with chromatin compaction assay; mouse hypomorphic knock-in with phenotyping and co-IP

    PMID:12167701 PMID:12183370

    Open questions at the time
    • Catalytic activity of Ring1B not yet identified
    • Direct target genes beyond Hox clusters unknown
  2. 2003 High

    Demonstrating Ring1B is essential for early development: Complete Rnf2 knockout caused gastrulation arrest that was partially rescued by Cdkn2a deletion, establishing that a key downstream effector of Ring1B-dependent Polycomb silencing is repression of the Ink4a/ARF cell-cycle inhibitor locus.

    Evidence Mouse knockout with genetic epistasis using Cdkn2a null allele

    PMID:12589020

    Open questions at the time
    • Enzymatic mechanism of Ring1B unknown
    • Whether phenotype is cell-autonomous unresolved
  3. 2004 High

    Identifying the catalytic activity: Ring1B was shown to be the E3 ubiquitin ligase that monoubiquitinates histone H2A at K119, with siRNA knockdown dramatically reducing global H2AK119ub, solving the long-standing question of which enzyme deposits this abundant histone mark.

    Evidence In vitro ubiquitination assay with purified hPRC1L complex; RNAi in HeLa cells; ChIP at Polycomb targets

    PMID:15386022

    Open questions at the time
    • Structural basis of Ring1B-BMI1 cooperation unknown
    • E2 enzyme specificity not defined
  4. 2006 High

    Solving the structural mechanism of allosteric activation: Two independent crystal structures of the Ring1B–BMI1 RING-RING heterodimer revealed that BMI1 stimulates Ring1B's ligase activity through a 'hugging' interaction; catalytic activity was mapped exclusively to Ring1B, with UbcH5a/b/c and UbcH6 identified as cognate E2 enzymes.

    Evidence X-ray crystallography at 2.5 Å by two independent groups; in vitro ubiquitination with mutagenesis

    PMID:16710298 PMID:16714294

    Open questions at the time
    • How the complex recognizes the nucleosome substrate unknown
    • Role of non-RING regions of Ring1B uncharacterized
  5. 2006 Medium

    Expanding the PRC1 landscape: A BCOR corepressor complex containing RNF2, RING1, RYBP, NSPC1, SKP1, and FBXL10 was identified, demonstrating that Ring1B participates in non-canonical PRC1 assemblies recruited by transcription factors like BCL6.

    Evidence Immunoprecipitation/mass spectrometry complex identification; ChIP at BCL6 target genes

    PMID:16943429

    Open questions at the time
    • Functional distinction between BCOR-PRC1 and canonical PRC1 unclear
    • Whether FBXL10 demethylase activity is coordinated with Ring1B ubiquitination unknown
  6. 2007 High

    Defining Ring1B's role in ES cell identity and PcG protein stability: Conditional Ring1B deletion in ES cells caused derepression of developmental genes and destabilization of other PcG proteins, revealing Ring1B as a structural hub of PRC1 integrity; Ring1B deposited H2AK119ub on the X chromosome but was dispensable for Xist-mediated silencing initiation.

    Evidence Conditional knockout ES cells with expression profiling, western blot for PcG stability, Xist induction assay

    PMID:17620408

    Open questions at the time
    • Whether Ring1B's stabilizing effect on other PcG proteins is direct or indirect unknown
    • Genome-wide Ring1B binding sites not yet mapped
  7. 2008 High

    Structural flexibility enables diverse partner recruitment: NMR showed the Ring1B C-terminal domain is conformationally flexible but rigidifies upon binding Polycomb cbox domains with nanomolar affinity, providing a mechanism for Ring1B to serve as a versatile scaffold recruiting distinct CBX subunits to PRC1.

    Evidence NMR spectroscopy; analytical ultracentrifugation; quantitative binding measurements

    PMID:18616292

    Open questions at the time
    • How competing CBX proteins are selected for specific PRC1 assemblies unknown
  8. 2010 High

    Revealing dual ubiquitin-based regulation of Ring1B stability and activity: Self-ubiquitination via K6/K27 chains was shown to stimulate Ring1B activity, while E6-AP-mediated K48 chains targeted it for degradation; USP7 counteracted both chain types, establishing a tripartite regulatory circuit controlling Ring1B protein levels and catalytic output in vivo.

    Evidence In vitro ubiquitination reconstitution identifying chain types; E6-AP knockout mice with elevated Ring1B/H2AK119ub; in vitro DUB assay with USP7

    PMID:20351251 PMID:20800574

    Open questions at the time
    • Whether USP7 discriminates between activating and degradative chains in vivo unresolved
    • Upstream signals controlling the balance between self-ubiquitination and E6-AP activity unknown
  9. 2012 High

    Defining variant PRC1 complexes and the RYBP stimulatory mechanism: Six distinct PRC1 complexes were catalogued, each with a unique PCGF subunit paired with RING1A/B; RYBP replaced CBX in non-canonical complexes and directly stimulated Ring1B catalytic activity; KDM2B/FBXL10 was shown to recruit non-canonical PRC1 to CpG islands genome-wide.

    Evidence Comprehensive proteomics; ChIP-seq; in vitro ubiquitination with RYBP; KDM2B conditional KO ES cells

    PMID:22325352 PMID:23395003

    Open questions at the time
    • How canonical and non-canonical PRC1 complexes partition genomic targets unresolved
    • Whether RYBP stimulation changes chain linkage or only rate unknown
  10. 2014 High

    Achieving atomic-resolution understanding of nucleosome recognition: The crystal structure of Ring1B–BMI1–UbcH5c bound to the nucleosome core particle revealed that substrate specificity arises from contacts distributed across Ring1B, UbcH5c, and BMI1 with nucleosomal DNA and the H2A/H4 acidic patch, with an unexpected direct role for the E2 in substrate recognition.

    Evidence X-ray crystallography of the complete E3–E2–nucleosome complex

    PMID:25355358

    Open questions at the time
    • How PRC1 transitions from chromatin compaction to ubiquitination mode unknown
    • Structural basis of variant PRC1 nucleosome recognition not determined
  11. 2015 High

    Expanding Ring1B function to DNA replication: Loss of RING1A/B caused replication fork stalling specifically at pericentromeric heterochromatin during mid S-phase, with targeted monoubiquitylation rescuing the defect, demonstrating that H2AK119ub facilitates replication through constitutive heterochromatin independently of canonical gene silencing.

    Evidence Conditional RING1A/B KO; DNA fiber analysis; targeted PCH ubiquitylation rescue; p21 epistasis

    PMID:26272920

    Open questions at the time
    • Mechanism by which H2AK119ub facilitates fork passage through heterochromatin unknown
    • Whether Ring1B is recruited to replication forks directly unresolved
  12. 2015 High

    Identifying catalytic-independent transcriptional activation: In melanoma, RNF2 was shown to drive CCND2 expression independently of its catalytic activity through MEK1-dependent phosphorylation that recruits UTX/p300, while simultaneously repressing LTBP2 via H2AK119ub, revealing bifunctional chromatin regulation by a single E3 ligase.

    Evidence Catalytic-dead mutant rescue; phospho-RNF2 co-IP with UTX/p300; ChIP; xenograft

    PMID:26450788

    Open questions at the time
    • Phosphorylation sites mediating UTX/p300 recruitment not mapped
    • Whether catalytic-independent activation is a general or context-specific mechanism unknown
  13. 2017 High

    Discovering non-canonical K33-linked ubiquitination of a non-histone substrate: RNF2 was found to catalyze K33-linked polyubiquitination of STAT1 at K379 after interferon stimulation, promoting STAT1/STAT2 dissociation from DNA and suppressing innate antiviral responses, establishing a direct role for RNF2 in innate immune regulation through a non-degradative, non-histone ubiquitin linkage.

    Evidence Screen of 115 RING E3 ligases; RNF2 KO; in vitro ubiquitination with K33 linkage identification; ChIP-seq for STAT1

    PMID:29242538

    Open questions at the time
    • Whether K33-linked ubiquitination requires a specific E2 partner distinct from canonical H2A ubiquitination unknown
    • Physiological significance in viral infection models in vivo not fully established
  14. 2018 High

    Suppressing transcription-replication conflicts at fragile sites: BMI1/RNF2 depletion increased RNA Pol II–replisome collisions and R-loop markers at common fragile sites, with genetic epistasis showing cooperation with FANCD2/FANCI, positioning PRC1 as a guardian of genome stability at replication-transcription interfaces.

    Evidence DNA fiber assay; proximity ligation assay for RNAPII–replisome; ChIP for FANCD2/RNH1; CRISPR KO; double depletion epistasis

    PMID:32142505

    Open questions at the time
    • Whether Ring1B's E3 activity or chromatin compaction function mediates TRC suppression unknown
    • Direct ubiquitination targets at fragile sites not identified
  15. 2020 Medium

    Co-option at active enhancers by an oncogenic transcription factor: In Ewing sarcoma, RING1B co-localized with EWSR1-FLI1 at active enhancers rather than repressed Polycomb targets, and was required for EWSR1-FLI1 enhancer recruitment and oncogenic gene expression, revealing context-dependent repurposing of PRC1 machinery for transcriptional activation.

    Evidence ChIP-seq co-localization; siRNA KD with xenograft; AURKB pharmacological perturbation

    PMID:33097530

    Open questions at the time
    • Mechanism by which RING1B facilitates EWSR1-FLI1 enhancer binding unknown
    • Whether H2AK119ub is deposited or absent at these active enhancers not resolved
  16. 2021 Medium

    Broadening the non-histone substrate repertoire: RNF2 was shown to ubiquitinate and degrade IRF4 in colon cancer, SIK1 in hepatocellular carcinoma, and RASSF10 in gastric cancer, establishing a pattern of RNF2 functioning as a conventional degradative E3 ligase for non-histone substrates in oncogenic contexts.

    Evidence Co-IP and ubiquitination assays for each substrate; epistasis rescue experiments; xenograft models

    PMID:27911266 PMID:34224728 PMID:34670117

    Open questions at the time
    • Whether non-histone ubiquitination occurs within or outside PRC1 complexes unknown
    • Chain linkage types for these substrates not determined
    • Independent replication across labs lacking for individual substrates

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how variant PRC1 complexes partition between canonical repressive and non-canonical activating functions genome-wide; the structural basis by which different PCGF subunits alter Ring1B substrate specificity; whether Ring1B's roles at replication forks and fragile sites require catalytic activity or chromatin compaction; and how post-translational modifications (phosphorylation, O-GlcNAcylation) coordinate Ring1B's diverse functions in different cellular contexts.
  • No genome-wide comparison of Ring1B substrates across variant PRC1 complexes
  • Structural models of variant PRC1–nucleosome complexes lacking
  • In vivo separation of catalytic vs. structural Ring1B functions at fragile sites not achieved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 11 GO:0016874 ligase activity 4 GO:0042393 histone binding 2 GO:0140110 transcription regulator activity 2 GO:0003677 DNA binding 1
Localization
GO:0005694 chromosome 4 GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3
Pathway
R-HSA-392499 Metabolism of proteins 6 R-HSA-4839726 Chromatin organization 6 R-HSA-1266738 Developmental Biology 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1640170 Cell Cycle 3 R-HSA-1643685 Disease 3 R-HSA-73894 DNA Repair 2 R-HSA-168256 Immune System 1
Partners
BCORBMI1KDM2BPCGF1RING1RYBPUBE3AUSP7
Complex memberships
BCOR complexKDM2B/FBXL10-PRC1 complexPRC1 (canonical, CBX-containing)PRC1 (non-canonical, RYBP-containing)

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 RNF2 (Ring2/Ring1B) is the catalytic E3 ubiquitin ligase subunit of the hPRC1L complex that monoubiquitinates nucleosomal histone H2A at lysine 119; siRNA knockdown of Ring2 dramatically reduces global H2AK119ub levels in HeLa cells, and the complex co-localizes with ubiquitinated H2A at Polycomb response elements and the Ubx promoter in Drosophila. Biochemical purification of hPRC1L complex, in vitro ubiquitination assay, RNAi knockdown, chromatin immunoprecipitation Nature High 15386022
2002 Ring1B (Rnf2) physically associates with other Polycomb group proteins (Rae28/Mph1, M33) and chromosomal DNA, and Ring1B hypomorphic mice display posterior homeotic transformations with mild Hox gene derepression; overexpression in chick embryos represses Hoxb9, establishing Ring1B as a Polycomb complex component regulating anterior-posterior axis specification. Co-immunoprecipitation, mouse hypomorphic knock-in, in ovo overexpression, in situ hybridization Development High 12183370
2003 Complete knockout of Rnf2 in mice causes gastrulation arrest and cell cycle inhibition; the early lethality is partially bypassed by genetic inactivation of the Cdkn2a (Ink4a/ARF) locus, implicating Polycomb-mediated repression of Cdkn2a as a key downstream effector of Ring1B during early development. Mouse knockout, genetic epistasis with Cdkn2a null allele, embryo phenotyping Proceedings of the National Academy of Sciences of the United States of America High 12589020
2005 Bmi-1 and Ring1A are positive regulators of H2A ubiquitylation within the PRC1 complex; Bmi-1 knockout results in significant loss of H2AK119ub and upregulation of Hoxc13 without affecting EZH2-mediated H3K27me3, placing H2A ubiquitylation downstream of H3K27 methylation in Polycomb silencing. Knockout mouse cells, ChIP, in vitro ubiquitination assay Molecular cell High 16359901
2006 Crystal structure of the Ring1B–Bmi1 RING-RING heterodimer was solved at 2.5 Å; Ring1B 'hugs' Bmi1 through RING-domain contacts and an N-terminal arm wrapping around Bmi1. Bmi1 enhances Ring1B E3 ligase activity toward H2A in vitro using E2s UbcH5a/b/c and UbcH6; catalytic activity resides in Ring1B, not Bmi1. Mutation of the E2/E3 interface in Ring1B abolishes activity. Crystal structure, in vitro ubiquitination reconstitution, active-site mutagenesis The EMBO journal High 16710298
2006 A 2.5-Å structure of the Bmi-1–Ring1B core domain complex reveals that Ring1B 'hugs' Bmi1 through RING and N-terminal tail contacts; this dual interaction synergistically stimulates Ring1B E3 ligase activity; modeling suggests the complex stabilizes E2–nucleosome interactions for efficient H2A ubiquitin transfer. X-ray crystallography (2.5 Å), in vitro ubiquitination assay, deletion mutagenesis The Journal of biological chemistry High 16714294
2007 Proteomics of in vivo biotinylated Ring1B/Rnf2 from erythroid cells identified ~50 interacting proteins, including previously unknown partners: histone demethylases LSD1/Aof2 and Fbxl10/Jhdm1B, casein kinase subunits, and the BCOR corepressor. A novel Ring1B–Fbxl10 complex also containing BcoR, CK2α, Skp1, and Nspc1/Pcgf1 was identified, extending Ring1B functions beyond canonical PRC1. In vivo biotinylation tagging, streptavidin affinity purification, mass spectrometry Molecular & cellular proteomics : MCP Medium 17296600
2007 Ring1B (Rnf2) deletion in mouse ES cells causes loss of several other PcG proteins (revealing a role in regulating PcG protein levels), derepression of lineage/developmental genes, and aberrant differentiation potential. Despite Ring1B being required for chromosome-wide H2AK119ub1 upon Xist expression, initiation of X-chromosome silencing by Xist is independent of Ring1B. Conditional knockout ES cells, gene expression profiling, western blot for PcG protein levels, Xist induction assay The Journal of cell biology High 17620408
2007 Prohibitin interacts with RNF2 via co-immunoprecipitation of endogenous proteins; the two proteins regulate E2F1 transcriptional activity via dual pathways (direct prohibitin-mediated and indirect p16-mediated); RNF2 and prohibitin are recruited together to E2F1-responsive promoters (by ChIP), and depletion of either increases p16 and decreases E2F1 activity. Co-immunoprecipitation (endogenous), ChIP, RNAi knockdown, luciferase reporter assay Oncogene Medium 17873902
2007 Ring1B is a direct substrate of caspases-3 and -9 both in vitro and in vivo; cleavage sites were mapped to Asp175 (caspase-3) and Asp208 (caspase-9); caspase cleavage redistributes Ring1B from exclusive nuclear localization throughout the entire cell and disrupts its transcriptional repression activity. In vitro caspase cleavage assay, site-directed mutagenesis of cleavage sites, subcellular localization by immunofluorescence, transcriptional repression assay Biochimica et biophysica acta High 17379327
2008 The C-terminal region of Ring1B (C-RING1B) binds the Polycomb cbox domain with 1:1 stoichiometry (Kd 9.2–180 nM depending on Pc orthologue); NMR reveals that C-RING1B is conformationally flexible alone but undergoes structural tightening upon cbox binding, with two conserved subdomains capable of intramolecular interaction that may allow Ring1B to recruit diverse PcG partners. NMR spectroscopy, analytical ultracentrifugation, binding affinity measurements Biochemistry High 18616292
2008 Ring1B/Rnf2 is required in vivo for three-dimensional genomic contraction and imprinted silencing at the Kcnq1 and Igf2r imprinted clusters in mouse embryos; Rnf2 and Ezh2 act independently to establish the repressive nuclear compartment associated with the paternal allele. Mouse embryo in vivo knockout, 3D-FISH for genomic contraction, allele-specific expression analysis Developmental cell High 18848501
2008 Ring1B ablation in mouse ES cells results in aberrant expression of key developmental genes (derepression), including TGFβ signaling and cell cycle genes, as well as downregulation of ES cell markers Sox2 and Rex-1; Ring1B-bound genes have bivalent histone marks (H3K4me3 + H3K27me3) or H3K4me3 alone at CpG-rich promoters. Conditional Ring1B knockout ES cells, genome-wide expression profiling, correlation with published ChIP-chip binding data PloS one Medium 18493325
2008 RNF2 interacts with PHB2 (prohibitin 2), and the RNF2–PHB2 complex represses CP2c-stimulated transcription in a PHB2 dose-dependent manner; the N-terminal 158 residues of RNF2 are sufficient for physical association and functional cooperation with PHB2, while CP2c binds the C-terminus of RNF2. Yeast two-hybrid, co-immunoprecipitation, deletion mutagenesis, luciferase reporter assay Molecular and cellular biochemistry Medium 18629613
2009 Ring1B/Rnf2 is required for self-renewal and multipotential ability of embryonic neural stem cells (NSCs); Ring1B-deficient NSCs show impaired proliferation in vivo and in neurosphere assays, unscheduled neuronal differentiation under proliferating conditions (enhanced when Ring1A is also deleted), upregulation of neuronal transcription factors and Cdkn1a/p21, and decreased Notch signaling effectors. Conditional knockout in neural stem cells, neurosphere assay, single-cell differentiation, in vivo BrdU labeling, mRNA analysis Stem cells (Dayton, Ohio) High 19544461
2009 RNF2 is phosphorylated at multiple serine residues; p38 MAPK inhibitor SB203580 blocks phosphorylation at Ser41 (a predicted p38 site confirmed by mass spectrometry in Sf9 cells), while MEK1/2 inhibitor PD98059 blocks the majority of RNF2 phosphorylation events; RNF2 phosphorylation differentially modulates transcription factor expression and histone H2B acetylation. 2D gel electrophoresis, phospho-specific western blot, kinase inhibitors, mass spectrometry identification of phosphorylation sites Proteomics Medium 19405034
2009 Bmi1 and Ring1B are expressed in pancreatic exocrine precursor cells and ductal/islet cells in adult pancreas; Ring1B expression is specifically and persistently upregulated only in high-grade PanINs and pancreatic ductal adenocarcinoma (distinct from Bmi1's earlier induction), and Bmi1 knockdown in acinar tumor cells alters expression of digestive enzymes, implicating PRC1 proteins in pancreatic disease progression. Immunohistochemistry in mouse models and human tissue, conditional KRas knock-in model, shRNA knockdown in cell lines The Journal of pathology Medium 19585519
2010 Ring1B self-ubiquitination generates K6-, K27-, and K48-based mixed polyubiquitin chains that stimulate (rather than degrade) its E3 ligase activity; E6-AP (UBE3A) ubiquitinates Ring1B on the same lysines to generate K48-linked chains targeting Ring1B for proteasomal degradation; inactivation of E6-AP in vivo elevates Ring1B and H2AK119ub levels and represses HoxB9 in cerebellar Purkinje neurons, with implications for Angelman syndrome. In vitro ubiquitination assay, E6-AP knockout mice, western blot, HoxB9 expression analysis Proceedings of the National Academy of Sciences of the United States of America High 20351251
2010 USP7 deubiquitinates Ring1B directly and specifically in vitro and in vivo; USP7-Ring1B interaction is mediated in part through Ring1B's RING domain; USP7 is found in a complex with other Polycomb proteins and has a stabilizing effect on Ring1B without discriminating between activating and proteolysis-targeting ubiquitin chains. In vitro deubiquitination assay, co-immunoprecipitation, RING domain interaction mapping Biochemical and biophysical research communications Medium 20800574
2011 Crystal structure of Bmi1/Ring1b RING-RING heterodimer in complex with E2 enzyme UbcH5c shows UbcH5c interacts exclusively with Ring1b; the Bmi1/Ring1b dimer binds duplex DNA through a basic surface patch unique to the heterodimer; mutation of DNA-binding residues abolishes H2A ubiquitination; computational modeling places the complex interacting with nucleosomal DNA and an acidic patch on histone H4 for substrate specificity. Crystal structure of E3-E2 complex, mutagenesis of DNA-binding surface, in vitro H2A ubiquitination assay, computational nucleosome docking The EMBO journal High 21772249
2011 Mathematical modeling of the Ring1B/Bmi1 ubiquitination system using biochemical data demonstrates that Ring1B can exhibit bistable switches, oscillations, and excitable (overshoot) transitions between distinct ubiquitination states (self-ubiquitinated active vs. E6-AP-ubiquitinated degradation-targeted); these dynamics can produce all-or-none H2A monoubiquitination rates and discrete periods of gene activity/inactivity controlled by abundances of Bmi1, Ring1B, E6-AP, and USP7. Computational/mathematical modeling constrained by biochemical data PLoS computational biology Low 22194680
2012 Six major PRC1 complexes each contain a distinct PCGF subunit with RING1A/B; RYBP (or YAF2) stimulates Ring1B H2AK119ub1 activity and defines non-canonical PRC1 complexes that exclude CBX/PHC/SCM; RYBP-containing and CBX-containing PRC1 complexes both compact chromatin but only RYBP stimulates Ring1B catalytic activity; RYBP knockdown in ES cells compromises embryoid body formation and H2AK119ub1 levels. Comprehensive proteomics, genome-wide ChIP-seq, in vitro ubiquitination assay with RYBP stimulation, ES cell differentiation assay, knockdown Molecular cell High 22325352
2013 RNF2 knockdown in cancer cells (HCT116) significantly inhibits cell proliferation, colony formation, and induces apoptosis in a partially p53-dependent manner; RNF2 directly binds both p53 and MDM2, promotes MDM2-mediated p53 ubiquitination, and increases MDM2 half-life by inhibiting its ubiquitination, thereby suppressing p53 protein levels during DNA damage response. RNAi knockdown, overexpression, p53 half-life and ubiquitination assays, co-immunoprecipitation, etoposide DNA damage model Oncogene Medium 23318437
2013 Fbxl10/Kdm2b recruits non-canonical PRC1 (containing Ring1B and Nspc1) to CpG islands genome-wide; Fbxl10 depletion causes major loss of Ring1B binding at target genes and loss of H2AK119ub1; Fbxl10's DNA binding capability and Ring1B integration are both required for ubiquitylation; Fbxl10-deficient ES cells cannot differentiate properly. Co-IP, genome-wide ChIP-seq, conditional KO ES cells, differentiation assay, in vitro ubiquitination with reconstituted complex Molecular cell High 23395003
2014 Crystal structure of the human Ring1B–Bmi1–UbcH5c E3-E2 complex bound to the nucleosome core particle reveals that the PRC1 ubiquitylation module achieves substrate specificity by contacting multiple nucleosome surfaces spatially distinct from the catalytic site; UbcH5c directly contacts the nucleosome (unexpected role for E2 in substrate recognition); the structure provides the mechanism of nucleosome recognition by PRC1 and insight into BRCA1's related H2A ubiquitylation. X-ray crystallography of PRC1-nucleosome co-complex Nature High 25355358
2014 In pancreatic ductal adenocarcinoma, Snail recruits Ring1B (and Ring1A) via its C-terminal zinc fingers to target promoters to repress gene expression and promote cell migration; Ring1B-mediated H2AK119ub1 is required for Snail-mediated transcriptional repression; EZH2 is required upstream for Snail-Ring1B recruitment; simultaneous depletion of Ring1A and Ring1B abolishes H2AK119ub1 at target promoters and compromises Snail-mediated cell migration. Co-immunoprecipitation, ChIP, siRNA knockdown of Ring1A/B, cell migration assay, H2AK119ub1 ChIP Cancer research Medium 24903147
2014 Ring1B is essential for expansion of hepatic stem/progenitor cells; conditional Ring1B knockout in mouse embryos inhibits hepatic stem/progenitor proliferation/differentiation and hepatic organogenesis via derepression of CDKIs Cdkn1a and Cdkn2a; clonal culture epistasis shows that simultaneous (not individual) suppression of Cdkn1a and Cdkn2a reverses the Ring1B-depletion cell cycle inhibition. Conditional mouse KO, clonal culture epistasis with Cdkn1a/Cdkn2a double knockdown, hepatic organogenesis phenotyping Hepatology (Baltimore, Md.) High 24497168
2015 RNF2 is oncogenic and prometastatic in melanoma via two distinct mechanisms: (1) RNF2-mediated H2AK119ub at the LTBP2 promoter silences this negative TGFβ regulator to drive invasion (requires catalytic activity); (2) RNF2 drives proliferation through direct transcriptional upregulation of CCND2 independently of catalytic activity. MEK1-mediated phosphorylation of RNF2 promotes recruitment of activating histone modifiers UTX and p300 to poised promoters to activate gene expression. Gain/loss-of-function studies in mouse and human melanoma cells, catalytic-dead mutant rescue, H2AK119ub ChIP, co-IP of UTX/p300 with phospho-RNF2, xenograft models Cancer discovery High 26450788
2015 RING1B O-GlcNAcylation at residues T250/S251 and S278 is identified in human ES cells; T250/S251 O-GlcNAcylation decreases during differentiation; ChIP-seq shows that non-O-GlcNAcylated RING1B is enriched near cell cycle genes, whereas O-GlcNAcylated RING1B preferentially targets neuronal genes, suggesting O-GlcNAc modification switches PRC1 genomic targeting during hESC differentiation. Point-mutation of O-GlcNAcylation sites, ChIP-seq, O-GlcNAc identification by mass spectrometry Stem cell research Medium 26100231
2015 RING1A and RING1B H2AK119ub activity at pericentromeric heterochromatin (PCH) is required for normal S-phase progression; loss of both RING1A and RING1B causes slow elongation and fork stalling preferentially at mid S-phase when PCH is replicated; acute senescence associated with RING1 loss is mediated by p21 (Cdkn1a) upregulation and can be uncoupled from DNA damage response; targeted monoubiquitylation of PCH via MBD1 rescues the replication defect. Conditional RING1A/B knockout, BrdU/EdU labeling, DNA fiber analysis, γH2AX immunostaining, chromocenter 3D-FISH, epistasis with p21 and targeted PCH ubiquitylation Journal of cell science High 26272920
2015 RNF2 knockdown in prostate cancer cells causes cell cycle arrest and apoptosis; tumor suppressor gene TXNIP is significantly upregulated upon RNF2 knockdown; ChIP shows RNF2 and H2AK119ub enrichment at the TXNIP promoter; simultaneous knockdown of RNF2 and TXNIP partially rescues the arrested cell cycle and apoptosis, placing TXNIP as a key downstream mediator of RNF2's oncogenic function in prostate cancer. RNAi knockdown, ChIP, double knockdown epistasis, xenograft, gene microarray Oncotarget Medium 28029659
2017 Nuclear RNF2 directly binds STAT1 after interferon stimulation and catalyzes K33-linked polyubiquitination of the STAT1 DNA-binding domain at K379, promoting STAT1/STAT2 dissociation from DNA and suppressing interferon-stimulated gene (ISG) transcription; RNF2 deficiency substantially enhances ISG expression and antiviral responses. High-content screening of 115 RING E3 ligases, RNF2 KO/KD, Co-IP of RNF2–STAT1, in vitro ubiquitination assay identifying K33-linked chains at K379, ChIP-seq for STAT1 DNA binding Nature immunology High 29242538
2017 RNF2 functions as an E3 ubiquitin ligase targeting SIK1 for proteasomal degradation in hepatocellular carcinoma; RNF2 directly physically interacts with SIK1; RNF2 expression is negatively correlated with SIK1 levels in HCC tissues; RNF2 knockdown reduces tumor growth and metastasis, which is rescued by simultaneous SIK1 knockdown. Co-immunoprecipitation, ubiquitination assay, RNAi knockdown, rescue epistasis, xenograft Oncotarget Medium 27911266
2018 Ring1A and Ring1B (RNF2) function as suppressors of transcription-replication conflicts (TRCs) and common fragile site (CFS) instability; BMI1/RNF2-depleted cells show slower replication forks, elevated fork stalling, increased RNA Pol II occupancy at CFSs, and increased associations between RNAPII and nascent replication forks (measured by proximity ligation assay); RNF2-KO cells show increased FANCD2 and RNH1 at CFSs consistent with R-loop accumulation; FANCD2/FANCI depletion further increases genomic instability in RNF2-KO cells. DNA fiber assay, proximity ligation assay (PLA) for RNAPII-replisome associations, ChIP for FANCD2/RNH1, CRISPR KO, double depletion epistasis PLoS genetics High 32142505
2020 RING1B is highly expressed in Ewing sarcoma (EwS) and co-localizes with EWSR1-FLI1 at active enhancers while retaining repressive activity at canonical Polycomb developmental target genes; RING1B is required for EWSR1-FLI1 recruitment to enhancers and expression of key oncogenic targets; RING1B knockdown impairs xenograft tumor growth; pharmacological AURKB inhibition increases H2AK119ub and downregulates RING1B/EWSR1-FLI1 common targets. ChIP-seq, siRNA knockdown, xenograft tumor model, AURKB pharmacological inhibition, gene expression profiling Science advances Medium 33097530
2021 RNF2 (Ring1B) promotes colon cancer progression by acting as an E3 ubiquitin ligase that directly interacts with and ubiquitinates IRF4, targeting it for proteasomal degradation; RNF2 overexpression enhances proliferation, migration, and invasion via IRF4 degradation; RNF2 knockdown causes opposite effects rescued by IRF4 co-knockdown. Co-immunoprecipitation, ubiquitination assay, RNAi knockdown, overexpression, xenograft, rescue epistasis Biochimica et biophysica acta. Molecular cell research Medium 34670117
2021 RASSF10 is a substrate for the E3 ubiquitin ligase RNF2; NPM-dependent downregulation of RNF2 is critical to maintain stable RASSF10 levels; RASSF10 promotes G2/M arrest via inhibition of Cdk1/cyclin-B and nuclear accumulation of GADD45a; this RASSF10/NPM/RNF2 cascade controls cell proliferation in gastric cancer. LC-MS/MS, live cell imaging, co-immunoprecipitation, ubiquitination assay, RNAi knockdown, cell cycle analysis The Journal of biological chemistry Medium 34224728
2021 Ring1b forms distinct complexes with either DEAD-box helicases (DDXs) or EMT transcription factors (EMT TFs) at specific loci on the E-cadherin promoter; DDX-Ring1b complexes moderately repress E-cadherin inducing a hybrid EMT state, while EMT TF-Ring1b complexes cooperate with DDX complexes for full repression in mesenchymal-like breast cancer cells, driving metastasis. Co-immunoprecipitation of distinct complexes, ChIP at E-cadherin promoter, RNAi knockdown, metastasis assay Cell death & disease Medium 33608512
2021 RNF2 overexpression in mammary carcinoma promotes cell proliferation, colony formation, migration, and invasion through downregulation of E-cadherin protein, implicating RNF2-driven EMT as a mechanism of breast cancer progression. RNF2 overexpression and knockdown in cell lines, western blot for E-cadherin, cell migration and invasion assays Pathology, research and practice Low 31300294
2023 A PROTAC degrader (MS147) targeting both BMI1 and RING1B via their interaction with EED (a PRC2 component) degrades BMI1/RING1B in an EED-, VHL-, ubiquitination-, and time-dependent manner; MS147 selectively reduces H2AK119ub without affecting H3K27me3, confirming RING1B as the H2AK119ub catalytic subunit, and inhibits proliferation of cancer cells insensitive to PRC2 inhibitors. PROTAC degrader chemistry, EED-VHL bifunctional molecule, H2AK119ub and H3K27me3 western blot, cancer cell proliferation assay Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 36737841
2012 In zebrafish, ring1b mutants show a severe craniofacial phenotype with near-complete absence of cranial cartilage, bone, and musculature; cranial neural crest cells migrate correctly into pharyngeal arches but fail to differentiate into chondrocytes; other neural crest-derived lineages (glia, neurons, chromatophores) are formed normally, revealing a specific role for Ring1b in promoting chondrocyte differentiation from CNC cells. Zebrafish ring1b mutant analysis, cell lineage tracing, in situ hybridization PloS one High 24040141
2012 Zebrafish ring1b is essential for pectoral fin development; lateral plate mesoderm differentiation into fin precursors is initiated normally, but fin bud outgrowth is impaired due to insufficient Fgf signaling activation; exogenous FGF4 or hyperactivated Wnt signaling (apc mutant) partially restores the fin program, establishing that PcG-mediated Ring1b gene regulation is required for sustained Fgf signaling in vertebrate limb development. Zebrafish ring1b mutant, FGF4 rescue experiment, genetic interaction with apc mutant, in situ hybridization for Fgf targets Development (Cambridge, England) High 22619390
2018 Ring1A and Ring1B repress Glis2 expression in MOZ-TIF2 AML stem cells; deletion of Ring1A/B diminishes self-renewal and induces numerous genes including Glis2; Glis2 overexpression causes differentiation of AML cells while Glis2 knockdown in Ring1A/B-deficient AML cells inhibits differentiation, demonstrating that Ring1A/B maintain AML stem cells partly by repressing Glis2. Conditional Ring1A/B knockout in AML mouse model, gene expression profiling, Glis2 overexpression and knockdown rescue Blood High 29371181
2019 RNF2 knockdown enhances radiosensitivity of squamous cell lung carcinoma cells by inhibiting irradiation-induced γH2AX foci formation and impairing interactions among ATM, MDC1, and H2AX; RNF2 knockdown combined with irradiation causes G1 arrest, increased apoptosis, and upregulation of p16 and Bax with downregulation of cyclin D2, CDK4, and Bcl-2. shRNA knockdown, clonogenic survival, co-immunoprecipitation of ATM-MDC1-H2AX, γH2AX foci counting, flow cytometry, xenograft Biochemistry and cell biology = Biochimie et biologie cellulaire Medium 30673298
2002 The core of the human Polycomb repressive complex (hPRC-H) was purified from HeLa cells and contains homologues of Drosophila PRC1 core proteins including RING1/Ring1B, with fewer non-PcG components than dPRC1; hPRC-H retains the ability to block nucleosomal array remodeling similarly to dPRC1, demonstrating functional conservation of the Ring1B-containing PRC1 complex between flies and humans. Biochemical purification from HeLa cells, chromatin compaction/remodeling assay Molecular and cellular biology High 12167701
2006 A BCOR complex contains Polycomb proteins RING1, RYBP, NSPC1, a Posterior Sex Combs homolog, and RNF2 as E3 ligase for H2A mono-ubiquitylation, as well as SKP1 and FBXL10 (a histone H3K36 demethylase); BCOR complex components and mono-ubiquitylated H2A co-localize at BCL6 target genes by ChIP, establishing that BCL6 can recruit PcG proteins including RNF2 to specific genomic loci. Immunoprecipitation/mass spectrometry complex identification, ChIP at BCL6 target genes Molecular and cellular biology Medium 16943429

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2004 Role of histone H2A ubiquitination in Polycomb silencing. Nature 1377 15386022
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 BAP1 links metabolic regulation of ferroptosis to tumour suppression. Nature cell biology 830 30202049
2005 Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. The Journal of clinical investigation 760 15931389
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 PCGF homologs, CBX proteins, and RYBP define functionally distinct PRC1 family complexes. Molecular cell 698 22325352
2005 Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Molecular cell 690 16359901
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2010 Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers. Cell 639 20850016
2005 High-throughput mapping of a dynamic signaling network in mammalian cells. Science (New York, N.Y.) 553 15761153
2005 Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF. Cell 551 15960975
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2006 Structure and E3-ligase activity of the Ring-Ring complex of polycomb proteins Bmi1 and Ring1b. The EMBO journal 372 16710298
2007 The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation. Nature 355 17468742
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2017 BAP1 regulates IP3R3-mediated Ca2+ flux to mitochondria suppressing cell transformation. Nature 330 28614305
2002 The core of the polycomb repressive complex is compositionally and functionally conserved in flies and humans. Molecular and cellular biology 319 12167701
2012 Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. PloS one 312 23251661
2013 Fbxl10/Kdm2b recruits polycomb repressive complex 1 to CpG islands and regulates H2A ubiquitylation. Molecular cell 299 23395003
2015 Loss of BAP1 function leads to EZH2-dependent transformation. Nature medicine 297 26437366
2003 Rnf2 (Ring1b) deficiency causes gastrulation arrest and cell cycle inhibition. Proceedings of the National Academy of Sciences of the United States of America 293 12589020
2006 Polycomb group and SCF ubiquitin ligases are found in a novel BCOR complex that is recruited to BCL6 targets. Molecular and cellular biology 283 16943429
2012 BIRC7-E2 ubiquitin conjugate structure reveals the mechanism of ubiquitin transfer by a RING dimer. Nature structural & molecular biology 281 22902369
2011 A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers. Nature 269 21654808
2014 Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome. Nature 266 25355358
2016 The cell proliferation antigen Ki-67 organises heterochromatin. eLife 265 26949251
2008 Polycomb group proteins Ezh2 and Rnf2 direct genomic contraction and imprinted repression in early mouse embryos. Developmental cell 259 18848501
2020 Biological Mechanisms and Clinical Significance of BAP1 Mutations in Human Cancer. Cancer discovery 231 32690542
2013 Tumours associated with BAP1 mutations. Pathology 222 23277170
2006 Structure of a Bmi-1-Ring1B polycomb group ubiquitin ligase complex. The Journal of biological chemistry 206 16714294
2007 Proteomics analysis of Ring1B/Rnf2 interactors identifies a novel complex with the Fbxl10/Jhdm1B histone demethylase and the Bcl6 interacting corepressor. Molecular & cellular proteomics : MCP 183 17296600
2016 BAP1/ASXL1 recruitment and activation for H2A deubiquitination. Nature communications 165 26739236
2017 Germline and somatic BAP1 mutations in high-grade rhabdoid meningiomas. Neuro-oncology 152 28170043
2007 Ring1B is crucial for the regulation of developmental control genes and PRC1 proteins but not X inactivation in embryonic cells. The Journal of cell biology 149 17620408
2020 BAP1: Not just a BRCA1-associated protein. Cancer treatment reviews 139 32877777
2021 Roles and mechanisms of BAP1 deubiquitinase in tumor suppression. Cell death and differentiation 134 33462414
2011 Recognition of UbcH5c and the nucleosome by the Bmi1/Ring1b ubiquitin ligase complex. The EMBO journal 134 21772249
2018 Mutant ASXL1 cooperates with BAP1 to promote myeloid leukaemogenesis. Nature communications 109 30013160
2011 An emerging model for BAP1's role in regulating cell cycle progression. Cell biochemistry and biophysics 102 21484256
2013 PBRM1 and BAP1 as novel targets for renal cell carcinoma. Cancer journal (Sudbury, Mass.) 98 23867514
2008 Ubiquitin E3 ligase Ring1b/Rnf2 of polycomb repressive complex 1 contributes to stable maintenance of mouse embryonic stem cells. PloS one 89 18493325
2017 SF3B1 and BAP1 mutations in blue nevus-like melanoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 85 28409567
2014 Germline BAP1 mutations predispose also to multiple basal cell carcinomas. Clinical genetics 83 25080371
2002 Involvement of the Polycomb-group gene Ring1B in the specification of the anterior-posterior axis in mice. Development (Cambridge, England) 83 12183370
2018 Overview of BAP1 cancer predisposition syndrome and the relationship to uveal melanoma. Journal of current ophthalmology 81 29988936
2010 Regulation of the polycomb protein Ring1B by self-ubiquitination or by E6-AP may have implications to the pathogenesis of Angelman syndrome. Proceedings of the National Academy of Sciences of the United States of America 81 20351251
2016 Gene of the month: BAP1. Journal of clinical pathology 76 27235536
2014 BRCA1-associated protein 1 (BAP1) deubiquitinase antagonizes the ubiquitin-mediated activation of FoxK2 target genes. The Journal of biological chemistry 74 25451922
2012 The ASXL-BAP1 axis: new factors in myelopoiesis, cancer and epigenetics. Leukemia 72 23147254
2021 Epigenetic targeted therapy of stabilized BAP1 in ASXL1 gain-of-function mutated leukemia. Nature cancer 68 35122023
2017 Diagnostic utility of BAP1 and EZH2 expression in malignant mesothelioma. Histopathology 67 27859460
2017 Nuclear RNF2 inhibits interferon function by promoting K33-linked STAT1 disassociation from DNA. Nature immunology 62 29242538
2014 Snail recruits Ring1B to mediate transcriptional repression and cell migration in pancreatic cancer cells. Cancer research 62 24903147
2010 Regulation of the Polycomb protein RING1B ubiquitination by USP7. Biochemical and biophysical research communications 62 20800574
2016 CDKN2A and BAP1 germline mutations predispose to melanoma and mesothelioma. Cancer letters 61 27181379
2017 BAP1, a tumor suppressor gene driving malignant mesothelioma. Translational lung cancer research 56 28713672
2015 Dual Roles of RNF2 in Melanoma Progression. Cancer discovery 56 26450788
2019 BRCA1-associated protein (BAP1)-inactivated melanocytic tumors. Journal of cutaneous pathology 53 31233225
2009 Maintenance of undifferentiated state and self-renewal of embryonic neural stem cells by Polycomb protein Ring1B. Stem cells (Dayton, Ohio) 53 19544461
2013 Knockdown of RNF2 induces apoptosis by regulating MDM2 and p53 stability. Oncogene 51 23318437
2019 BAP1 Loss Is Associated with DNA Methylomic Repatterning in Highly Aggressive Class 2 Uveal Melanomas. Clinical cancer research : an official journal of the American Association for Cancer Research 49 31285370
2021 BAP1-Mutated Clear Cell Renal Cell Carcinoma. American journal of clinical pathology 46 33210135
2007 Prohibitin interacts with RNF2 and regulates E2F1 function via dual pathways. Oncogene 46 17873902
2021 Roles of the BAP1 Tumor Suppressor in Cell Metabolism. Cancer research 45 33446574
2021 Estimation of the timing of BAP1 mutation in uveal melanoma progression. Scientific reports 45 33903674
2009 The epigenetic regulators Bmi1 and Ring1B are differentially regulated in pancreatitis and pancreatic ductal adenocarcinoma. The Journal of pathology 44 19585519
2020 BAP1: role in carcinogenesis and clinical implications. Translational lung cancer research 40 32206571
2015 Stabilization of MCRS1 by BAP1 prevents chromosome instability in renal cell carcinoma. Cancer letters 39 26300492
2013 The polycomb group protein ring1b/rnf2 is specifically required for craniofacial development. PloS one 37 24040141
2017 Polycomb Group Proteins RING1A and RING1B Regulate the Vegetative Phase Transition in Arabidopsis. Frontiers in plant science 36 28596781
2016 BAP1 suppresses lung cancer progression and is inhibited by miR-31. Oncotarget 36 26885612
2003 DING, a genistein target in human breast cancer: a protein without a gene. The Journal of nutrition 36 12840230
2020 BAP1 suppresses prostate cancer progression by deubiquitinating and stabilizing PTEN. Molecular oncology 35 33155366
2018 Reversal of cisplatin resistance by microRNA-139-5p-independent RNF2 downregulation and MAPK inhibition in ovarian cancer. American journal of physiology. Cell physiology 35 29719173
2017 Knockdown of RNF2 induces cell cycle arrest and apoptosis in prostate cancer cells through the upregulation of TXNIP. Oncotarget 35 28029659
2017 Down-regulation of salt-inducible kinase 1 (SIK1) is mediated by RNF2 in hepatocarcinogenesis. Oncotarget 32 27911266
2015 Analysis of BAP1 Germline Gene Mutation in Young Uveal Melanoma Patients. Ophthalmic genetics 32 25687217
2015 RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells. Stem cell research 32 26100231
2011 Switches, excitable responses and oscillations in the Ring1B/Bmi1 ubiquitination system. PLoS computational biology 30 22194680
2022 The expanding role of BAP1 in clear cell renal cell carcinoma. Human pathology 29 35932824
2021 Emerging role of RNF2 in cancer: From bench to bedside. Journal of cellular physiology 29 33400276
2020 Tumor-derived neomorphic mutations in ASXL1 impairs the BAP1-ASXL1-FOXK1/K2 transcription network. Protein & cell 29 32683582
2019 LncRNA-MEG3 inhibits cell proliferation and invasion by modulating Bmi1/RNF2 in cholangiocarcinoma. Journal of cellular physiology 29 31119760
2021 BAP1 forms a trimer with HMGB1 and HDAC1 that modulates gene × environment interaction with asbestos. Proceedings of the National Academy of Sciences of the United States of America 28 34815344
2019 BAP1 promotes stalled fork restart and cell survival via INO80 in response to replication stress. The Biochemical journal 28 31657441
2015 Polycomb RING1A- and RING1B-dependent histone H2A monoubiquitylation at pericentromeric regions promotes S-phase progression. Journal of cell science 28 26272920
2020 RING1B recruits EWSR1-FLI1 and cooperates in the remodeling of chromatin necessary for Ewing sarcoma tumorigenesis. Science advances 27 33097530
2018 Ring1A and Ring1B inhibit expression of Glis2 to maintain murine MOZ-TIF2 AML stem cells. Blood 26 29371181
2023 BAP1 promotes osteoclast function by metabolic reprogramming. Nature communications 24 37740028
2020 Transcription-replication conflicts as a source of common fragile site instability caused by BMI1-RNF2 deficiency. PLoS genetics 24 32142505
2019 Digital Image Analysis of BAP-1 Accurately Predicts Uveal Melanoma Metastasis. Translational vision science & technology 23 31110912
2015 A novel BAP1 mutation is associated with melanocytic neoplasms and thyroid cancer. Cancer genetics 23 26774355
2009 RNF2 is the target for phosphorylation by the p38 MAPK and ERK signaling pathways. Proteomics 23 19405034
2021 Circ_0004104 Accelerates the Progression of Gastric Cancer by Regulating the miR-539-3p/RNF2 Axis. Digestive diseases and sciences 22 33449226
2021 Co-occurrence of BAP1 and SF3B1 mutations in uveal melanoma induces cellular senescence. Molecular oncology 22 34706158
2012 The Polycomb group protein Ring1b is essential for pectoral fin development. Development (Cambridge, England) 21 22619390
2023 Targeted Degradation of PRC1 Components, BMI1 and RING1B, via a Novel Protein Complex Degrader Strategy. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20 36737841
2021 Novel insights into the BAP1-inactivated melanocytic tumor. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 20 34857909
2018 The Polycomb proteins RING1B and EZH2 repress the tumoral pro-inflammatory function in metastasizing primary cutaneous squamous cell carcinoma. Carcinogenesis 18 29394319
2008 Structural transitions of the RING1B C-terminal region upon binding the polycomb cbox domain. Biochemistry 18 18616292
2008 PHB2 interacts with RNF2 and represses CP2c-stimulated transcription. Molecular and cellular biochemistry 18 18629613
2024 Tumor suppressor BAP1 suppresses disulfidptosis through the regulation of SLC7A11 and NADPH levels. Oncogenesis 17 39266549
2023 Genetic screens reveal new targetable vulnerabilities in BAP1-deficient mesothelioma. Cell reports. Medicine 17 36657447
2018 G-quadruplexes in the BAP1 promoter positively regulate its expression. Experimental cell research 17 29787736
2022 Intrinsic Disorder in BAP1 and Its Association with Uveal Melanoma. Genes 16 36292588
2022 BAP1 in cancer: epigenetic stability and genome integrity. Discover oncology 16 36318367
2021 Intratumor Heterogeneity in Uveal Melanoma BAP-1 Expression. Cancers 15 33800007
2021 The AMP-dependent kinase pathway is upregulated in BAP1 mutant uveal melanoma. Pigment cell & melanoma research 15 34347929
2021 RNF2 promotes the progression of colon cancer by regulating ubiquitination and degradation of IRF4. Biochimica et biophysica acta. Molecular cell research 15 34670117
2020 BAP1 maintains chromosome stability by stabilizing DIDO1 in renal cell carcinoma. American journal of cancer research 15 32509391
2016 Radiosensitization of esophageal carcinoma cells by knockdown of RNF2 expression. International journal of oncology 15 26936624
2022 Pyruvate dehydrogenase inactivation causes glycolytic phenotype in BAP1 mutant uveal melanoma. Oncogene 14 35046531
2021 BAP1 promotes viability and migration of ECA109 cells through KLF5/CyclinD1/FGF-BP1. FEBS open bio 14 33529461
2021 The spectrum of tumors harboring BAP1 gene alterations. Cancer genetics 14 33866194
2021 Molecular basis for RASSF10/NPM/RNF2 feedback cascade-mediated regulation of gastric cancer cell proliferation. The Journal of biological chemistry 14 34224728
2014 Ring1B promotes hepatic stem/progenitor cell expansion through simultaneous suppression of Cdkn1a and Cdkn2a in mice. Hepatology (Baltimore, Md.) 14 24497168
2022 Tumor suppressor BAP1 nuclear import is governed by transportin-1. The Journal of cell biology 13 35446349
2021 Distinct Ring1b complexes defined by DEAD-box helicases and EMT transcription factors synergistically enhance E-cadherin silencing in breast cancer. Cell death & disease 13 33608512
2021 Regulation of B Lymphocyte Development by Histone H2A Deubiquitinase BAP1. Frontiers in immunology 13 33912157
2019 Knockdown of RNF2 enhances the radiosensitivity of squamous cell carcinoma in lung. Biochemistry and cell biology = Biochimie et biologie cellulaire 13 30673298
2019 The oncogenic impact of RNF2 on cell proliferation, invasion and migration through EMT on mammary carcinoma. Pathology, research and practice 13 31300294
2007 Polycomb group protein RING1B is a direct substrate of Caspases-3 and -9. Biochimica et biophysica acta 13 17379327