Affinage

RYBP

RING1 and YY1-binding protein · UniProt Q8N488

Length
228 aa
Mass
24.8 kDa
Annotated
2026-06-10
81 papers in source corpus 41 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RYBP is an intrinsically disordered, ubiquitin-binding protein that serves as a core subunit of variant/non-canonical PRC1 complexes, where it directs the deposition and self-propagation of the repressive H2AK119ub1 histone mark across Polycomb chromatin domains (PMID:19170609, PMID:22325352, PMID:32203418). RYBP associates with all six PCGF-RING1A/B combinations to form variant PRC1 complexes that are mutually exclusive with canonical CBX/PHC-containing PRC1, and uniquely stimulates RING1B E3 ubiquitin ligase activity toward H2AK119, an activity CBX-PRC1 complexes lack (PMID:22325352). It deposits H2AK119ub1 at Polycomb targets independently of PRC2 and H3K27me3 (PMID:22325148, PMID:22269950), yet RYBP/YAF2-dependent ligase activity also underpins activity-based communication between PRC1 and PRC2 required to maintain normal H3K27me3 domains (PMID:27705745). RYBP reads H2AK119ub1 on modified nucleosomes and, through combined recognition of ubiquitin and the nucleosome acidic patch, positions RING1B to ubiquitinate neighboring unmodified nucleosomes, establishing the structural basis of a read-write positive-feedback loop that propagates the mark through cell division (PMID:32203418, PMID:38528151). This Polycomb function makes RYBP essential for early embryogenesis and for governing lineage decisions including cardiac, neural, hematopoietic, and mesodermal differentiation (PMID:16055728, PMID:26110923, PMID:30560907, PMID:37935677). Beyond PRC1, RYBP acts in transcription-factor complexes—bridging YY1 with E2F2/3 or GABP to regulate target promoters (PMID:12411495, PMID:11953439)—and operates in PRC1-independent contexts at p53, where it inhibits MDM2-mediated p53 ubiquitination to stabilize p53 (PMID:19098711), and at the DNA damage response, where its NZF domain binds K63-linked ubiquitin chains and high RYBP levels inhibit ATM/BRCA1 recruitment to impair homologous recombination (PMID:29320735, PMID:36233063). Nuclear import of this disordered protein is mediated by importin α3 acting on N-terminal NLS elements (PMID:27989698, PMID:33945888). Heterozygous de novo variants in the N-terminal zinc-finger/ubiquitin-binding domain of RYBP cause a syndromic neurodevelopmental disorder (PMID:39891528).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1999 High

    Establishing RYBP as a physical partner of mammalian Polycomb components and YY1 placed it within both Polycomb repression and sequence-specific transcription, defining its dual axis of action.

    Evidence Yeast two-hybrid and direct binding assays with Ring1A/B, M33/CBX2 and YY1, plus transcriptional repression in transfected cells

    PMID:10369680

    Open questions at the time
    • Did not define which complex RYBP acts in
    • No information on enzymatic role or chromatin marks
  2. 2002 High

    Identifying RYBP as a bridging adaptor between YY1 and other transcription factors (E2F2/3, GABP) showed it can assemble combinatorial transcription-factor complexes and act as either repressor or coactivator depending on context.

    Evidence Yeast two/three-hybrid bridging assays, Co-IP, ChIP at the Cdc6 promoter and promoter activity assays

    PMID:11953439 PMID:12411495

    Open questions at the time
    • How RYBP switches between activating and repressive outcomes is unresolved
    • Link to Polycomb activity not addressed in these contexts
  3. 2005 High

    Loss-of-function genetics in mouse and Drosophila established that RYBP is essential for early development and functions as a Polycomb-dependent repressor in vivo, moving it from interaction partner to physiologically required regulator.

    Evidence Mouse knockout with chimeric analysis and Drosophila GAL4/UAS overexpression with PcG-dependent repression readouts

    PMID:16055728 PMID:16125914

    Open questions at the time
    • Molecular basis of developmental phenotypes not defined
    • Drosophila evidence is Medium-confidence epistasis
  4. 2006 Medium

    Demonstrating that RYBP binds ubiquitinated histone H2A and is itself ubiquitinated by Ring1B provided the first hint that RYBP both reads and is regulated by the H2A ubiquitin mark.

    Evidence In vitro ubiquitin binding assays, immunoprecipitation and domain mapping

    PMID:17070805

    Open questions at the time
    • Linkage type of bound ubiquitin not yet defined
    • Functional consequence of RYBP ubiquitination unresolved
  5. 2009 High

    Showing that RYBP is natively unfolded and folds upon binding RING1B or DNA explained how a single small protein engages structurally diverse partners.

    Evidence Multiple biophysical methods (CD, NMR, FTIR, fluorescence, analytical ultracentrifugation)

    PMID:19170609

    Open questions at the time
    • Conformations adopted with most partners not structurally resolved
    • Does not address chromatin-bound state
  6. 2008 Medium

    Defining a PRC1-independent role in stabilizing p53 by inhibiting MDM2-mediated ubiquitination established RYBP as a node in the DNA-damage/cell-cycle response.

    Evidence Co-IP, ubiquitination assays, cell-cycle and DNA damage assays

    PMID:19098711

    Open questions at the time
    • Whether RYBP directly competes with or inhibits MDM2 enzymatically unresolved
    • In vivo relevance to p53 tumor suppression not tested
  7. 2012 High

    Biochemical reconstitution and ChIP-seq established the central mechanistic identity of RYBP: a variant-PRC1 subunit that specifically stimulates RING1B H2AK119 ubiquitin ligase activity and deposits the mark independently of PRC2/H3K27me3, distinct from chromatin-targeting CBX-PRC1.

    Evidence Proteomics/Co-IP, in vitro ubiquitin ligase assays, ChIP-seq in wild-type and PRC2-deficient mESCs, RNAi knockdown

    PMID:22269950 PMID:22325148 PMID:22325352 PMID:23273917

    Open questions at the time
    • How RYBP-PRC1 is recruited to target chromatin in absence of CBX not fully resolved
    • Structural basis of ligase stimulation not yet defined
  8. 2016 High

    Conditional KO with in vitro ligase assays showed RYBP/YAF2-dependent stimulation defines PRC1 H2AK119 activity and drives activity-based PRC1-to-PRC2 communication needed to maintain H3K27me3 domains.

    Evidence Conditional RYBP KO mESCs, ChIP-seq, in vitro ubiquitin ligase assays

    PMID:27705745

    Open questions at the time
    • Molecular reader linking H2AK119ub1 to PRC2 recruitment not specified here
    • YAF2 vs RYBP functional distinction not resolved
  9. 2016 Medium

    Mapping three N-terminal NLS elements and a cytoplasmic mutant linked RYBP subcellular localization to its choice between nuclear Polycomb function and cytoplasmic apoptotic/p53-regulatory activity.

    Evidence NLS mutagenesis, EGFP-fusion localization, Co-IP and functional ubiquitination/apoptosis assays

    PMID:27989698

    Open questions at the time
    • Physiological signals controlling RYBP localization unknown
    • Single-lab functional consequences
  10. 2018 High

    Showing that the NZF domain preferentially binds K63-linked ubiquitin chains and that high RYBP inhibits BRCA1 recruitment and end resection placed RYBP as a modulator of homologous recombination repair.

    Evidence In vitro ubiquitin chain binding assays with mutagenesis, live-cell imaging, chromatin fractionation, HR repair assays

    PMID:29320735

    Open questions at the time
    • Whether endogenous RYBP normally restrains HR is not established
    • Relationship between K63-chain binding and H2AK119ub1 reading unresolved
  11. 2020 High

    Demonstrating that RYBP and YAF2 bind H2AK119ub1 to recruit PRC1 to neighboring nucleosomes formalized a positive-feedback read-write model for mark propagation, aided by H1-dependent chromatin compaction.

    Evidence In vitro nucleosome binding, cell-based propagation assays, H1 knockdown, ChIP

    PMID:32203418

    Open questions at the time
    • Structural basis of nucleosome engagement not yet resolved at this step
    • Quantitative limits of spreading distance unclear
  12. 2023 High

    Atomic-resolution structure resolved how RYBP-PRC1 switches from RING1B-mediated binding of unmodified nucleosomes to RYBP-mediated recognition of ubiquitin plus the acidic patch, mechanistically explaining the H2Aub1 read-write feedback loop.

    Evidence Crystallography/cryo-EM with biochemical binding assays and mutational analysis

    PMID:38528151

    Open questions at the time
    • Structure of full vPRC1 with additional PCGF subunits not resolved
    • Dynamics of the read-to-write switch not directly visualized
  13. 2021 Medium

    ITC and structural analysis of the RYBP NLS with importin α3 defined the molecular basis of its nuclear import, complementing earlier NLS mapping.

    Evidence Fluorescence spectroscopy, CD, ITC and molecular docking of the NLS peptide with Impα3

    PMID:33945888

    Open questions at the time
    • Regulation of import in response to cellular state unknown
    • Full-length import kinetics not measured
  14. 2021 Medium

    PRC1-independent control of Notch via direct interaction with CIR1 and of Wnt-dependent differentiation programs broadened RYBP's mechanistic repertoire beyond histone ubiquitination.

    Evidence Conditional KO in neural progenitors, Co-IP, ChIP, genetic Hes5 rescue (Notch) and ChIP-seq/RNA-seq (Wnt)

    PMID:34798064 PMID:37935677

    Open questions at the time
    • Direct biochemical mechanism linking RYBP to Wnt pathway not fully defined
    • Extent of PRC1-independence in vivo varies by context
  15. 2024 Medium

    Identifying RYBP cooperation with the TrxG component WDR5 at super-enhancers and with NKX2-5/BRACHYURY at developmental loci showed RYBP can support transcriptional activation, not only repression, balancing TrxG and PcG at target genes.

    Evidence ChIP-seq, RNA-seq, HiChIP, promoter reporter assays and Co-IP in ESCs and lineage models

    PMID:36751888 PMID:39604829 PMID:39676794 PMID:42049912

    Open questions at the time
    • How RYBP partitions between activating and repressive complexes mechanistically unresolved
    • Several partner interactions from single labs
  16. 2025 Medium

    Establishing heterozygous de novo N-terminal RYBP variants as the cause of a syndromic neurodevelopmental disorder provided direct human-genetic evidence that RYBP dosage and domain function are essential for development.

    Evidence Patient variant identification, in vitro binding assays, Drosophila overexpression, DNA methylation episignature

    PMID:39891528

    Open questions at the time
    • Mechanism by which C44W reduces protein function despite retained binding unclear
    • Genotype-phenotype correlations across patients not fully defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RYBP is selectively recruited to specific target chromatin in the absence of CBX-type readers, and how it is dynamically partitioned between repressive vPRC1 and activating TrxG/transcription-factor complexes, remains the central open question.
  • No defined sequence-specific recruitment determinant for vPRC1
  • Switch governing activator-versus-repressor function unresolved
  • In vivo significance of many partner interactions untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0140110 transcription regulator activity 4 GO:0042393 histone binding 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0000228 nuclear chromosome 4 GO:0005634 nucleus 3 GO:0005829 cytosol 2
Pathway
R-HSA-4839726 Chromatin organization 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1266738 Developmental Biology 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-73894 DNA Repair 2
Partners
CBX2E2F3KDM2BMDM2PCGF5RING1ARING1BYY1
Complex memberships
variant/non-canonical PRC1 (RYBP-PRC1)

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 RYBP directly interacts with Ring1A, Ring1B, and M33 (CBX2) — components of mammalian Polycomb complexes — as well as with the transcription factor YY1, and acts as a transcriptional repressor in transiently transfected cells. Yeast two-hybrid screen, direct protein interaction assays, transient transfection transcriptional repression assay The EMBO journal High 10369680
2002 RYBP interacts specifically with E2F2 and E2F3 (via their marked box domains) and mediates formation of a ternary complex with YY1, enabling synergistic activation of the Cdc6 promoter at G1/S; both E2F2/E2F3, YY1, and RYBP associate with the Cdc6 promoter at G1/S by ChIP. Yeast two-hybrid, co-immunoprecipitation, chromatin immunoprecipitation (ChIP), promoter activity assays The EMBO journal High 12411495
2002 RYBP (as YEAF1) interacts with both YY1 and hGABPβ (E4TF1), acting as a bridging factor that enables complex formation between these two structurally distinct transcription factors; YEAF1 negatively regulates hGABP transcriptional activity, whereas its homolog YAF2 positively regulates it. Yeast two-hybrid, yeast three-hybrid assay, in vitro and in vivo binding assays The Journal of biological chemistry High 11953439
2005 Rybp null mice die at early postimplantation stage with defective extraembryonic structures and failed decidualization; chimeric analysis revealed Rybp-deficient cells cause forebrain overgrowth and neural tube closure defects, establishing Rybp as essential for early embryogenesis and CNS development. Homologous recombination knockout in ES cells, chimeric mouse analysis, histology Molecular and cellular biology High 16055728
2005 Drosophila dRYBP functions as a transcriptional repressor in vivo in a Polycomb group gene-dependent manner; overexpression in haltere discs represses Ultrabithorax expression in a Polycomb-dependent fashion. GAL4/UAS overexpression, in vivo transcriptional repression assay, RNA in situ hybridization, anti-dRYBP antibody Mechanisms of development Medium 16125914
2006 RYBP is a ubiquitin-binding protein; its ubiquitin-binding domain binds ubiquitinated histone H2A, and Ring1B (a known E3 ubiquitin ligase that interacts with RYBP) promotes RYBP ubiquitination. In vitro ubiquitin binding assays, immunoprecipitation, functional domain mapping FEBS letters Medium 17070805
2007 Rybp interacts with Hippi (a protein involved in Huntington's disease and neuronal apoptosis), synergizes with Hippi to enhance Caspase-8-mediated apoptosis, and may mediate/regulate the Hippi–Caspase-8 interaction; Rybp and Hippi co-localize in a subset of neurons in the developing mouse brain. Co-immunoprecipitation, functional apoptosis assays, immunofluorescence co-localization Apoptosis : an international journal on programmed cell death Medium 17874297
2007 Loss of a single Rybp allele in mice causes retinal coloboma with perturbed Pax6 localization; chimeric Rybp-null cells cause coloboma and malformed lenses; tissue-specific Rybp overexpression in the lens causes abnormal fiber cell differentiation and lens opacification with altered AP-2α, Sox2, and βA4-crystallin expression. Conditional and conventional knockout mice, chimeric embryo analysis, transgenic overexpression, histology BMC developmental biology Medium 17470285
2008 RYBP interacts with MDM2, inhibits MDM2-mediated p53 ubiquitination, leading to p53 stabilization and increased p53 activity; RYBP induces cell-cycle arrest and participates in the p53 response to DNA damage. Co-immunoprecipitation, ubiquitination assays, cell-cycle analysis, DNA damage assays EMBO reports Medium 19098711
2009 RYBP is a natively unfolded/intrinsically disordered protein that acquires a folded conformation upon binding to the C-terminal domain of Ring1B or to DNA, providing a structural basis for its engagement with diverse partners. Fluorescence spectroscopy, circular dichroism, FTIR, NMR spectroscopy, analytical ultracentrifugation, DOSY-NMR, gel filtration chromatography Biochemistry High 19170609
2012 RYBP associates with all six PCGF-RING1A/B combinations to form variant PRC1 complexes that are mutually exclusive with CBX/PHC/SCM-containing canonical PRC1 complexes; RYBP stimulates Ring1B E3 ubiquitin ligase activity toward H2AK119ub1 whereas CBX proteins do not; RYBP knockdown in ESCs reduces H2AK119ub1 levels and impairs embryoid body formation. Comprehensive proteomics (co-immunoprecipitation/mass spectrometry), genomics, in vitro ubiquitin ligase assay, RNAi knockdown Molecular cell High 22325352
2012 RYBP-PRC1 (comprising RING1B and RYBP) mediates H2A monoubiquitylation at Polycomb target sites in mouse ESCs independently of PRC2 and H3K27me3; RYBP-PRC1 is also involved in Xist RNA-mediated silencing. ChIP-seq in wild-type and PRC2-deficient mESCs, Co-immunoprecipitation, functional gene silencing assays Cell High 22325148
2012 RYBP represses endogenous retroviruses (MuERV class) and preimplantation/germ line-specific genes in mouse ESCs independently of H3K27me3 (shown using Eed-KO ESCs); RYBP binding to promoters is independent of H3K27me3, and absence of RYBP does not alter Ring1B or Mel18 recruitment to Polycomb targets. Conditional RYBP knockout ESCs, genome-wide ChIP-seq, Eed-KO genetic control Molecular and cellular biology High 22269950
2012 In mouse ESCs, Cbx7-PRC1 requires Cbx7 for Ring1B chromatin recruitment, whereas RYBP-PRC1 enhances PRC1 enzymatic (H2AK119ub) activity; genes occupied by RYBP show lower Ring1B/H2AK119ub and are more transcriptionally active; RYBP- and Cbx7-containing complexes regulate distinct gene sets governing metabolism/cell cycle vs. early lineage commitment. ChIP-seq, Co-immunoprecipitation, RNAi knockdown, gene expression profiling in mESCs Cell reports High 23273917
2012 Rybp is a direct target of miR-29; Rybp and YY1 co-occupy myogenic loci including miR-29 to repress their expression; Rybp overexpression enhances Ezh2 enrichment and H3K27me3 at target loci; Rybp acts as a negative regulator of skeletal myogenesis in vitro and in vivo. 3′UTR luciferase reporter assay, ChIP, overexpression/knockdown in C2C12 cells, in vivo muscle regeneration model The Journal of biological chemistry High 22661705
2015 RYBP is required for cardiac differentiation of mouse ESCs: Rybp null ESCs fail to form rhythmically beating cardiomyocytes; key cardiac transcription factors (Plagl1, Isl1, Tnnt2) are downregulated; germline-specific markers are upregulated; re-expression of Rybp by lentiviral vector rescues the phenotype. Rybp null ESC cardiac differentiation assay, gene expression profiling (transcriptome), lentiviral rescue Stem cells and development High 26110923
2015 Conditional inactivation of Rybp in adult hematopoiesis causes reversion of B-1-to-B-2 B-cell progenitor ratios (increased B-1, loss of pre-proB/B-2 progenitors); this effect did not change global H2AUb and did not genetically interact with Ring1A or Ring1B deletion, suggesting a Polycomb-independent mechanism. Conditional knockout mouse model, flow cytometry, in vitro progenitor assays, genetic epistasis with Ring1A/B knockouts Molecular and cellular biology High 26711264
2016 RYBP/YAF2-dependent stimulation defines the H2AK119 E3 ubiquitin ligase activity of PRC1; in mESCs, RYBP shapes H2AK119ub1 at PcG targets and underpins activity-based communication between PRC1 and PRC2 required for normal H3K27me3; without this communication, Polycomb chromatin domains erode and target genes are susceptible to inappropriate expression. Conditional RYBP KO mESCs, ChIP-seq, in vitro ubiquitin ligase assays, genetic manipulation eLife High 27705745
2016 RYBP harbors three functional monopartite nuclear localization signals (NLSs) at its N-terminus; a cytoplasm-localized mutant (RYBPmut) with NLS disruption more potently binds caspase-8, prevents MDM2-mediated p53 ubiquitination, and induces apoptosis compared to nuclear wild-type RYBP. Deletion/point mutation analysis, EGFP-fusion localization, co-immunoprecipitation, ubiquitination assays, apoptosis assays Cellular signalling Medium 27989698
2016 RYBP interacts with FANK1 via its Ser/Thr-rich C-terminal region binding FANK1's FNIII domain; RYBP stabilizes FANK1 by inhibiting its proteasome-mediated degradation; the RYBP–FANK1 interaction activates AP-1 signaling, contributing to tumor cell apoptosis. Yeast two-hybrid, co-immunoprecipitation, GST pulldown, immunofluorescence, protein stability assays, AP-1 reporter assay Cellular signalling Medium 27060496
2017 DDX5 inhibits reprogramming by repressing RYBP expression via miR-125b processing; Ddx5 disruption upregulates Rybp, which suppresses lineage-specific genes through H2AK119 ubiquitination; RYBP is also required for PRC1-independent OCT4 recruitment to the Kdm2b promoter during reprogramming. Genetic knockdown/overexpression, ChIP, miRNA processing assays, iPSC reprogramming efficiency assays Cell stem cell Medium 28111200
2018 RYBP preferentially binds K63-linked ubiquitin chains via its NZF (Npl4 zinc finger) domain; RYBP is K48-polyubiquitylated by RNF8 and rapidly removed from chromatin after DNA double-strand breaks by VCP/p97 segregase; high RYBP expression inhibits BRCA1 complex recruitment and reduces DNA end resection, impairing homologous recombination repair. In vitro ubiquitin chain binding assays, live-cell imaging, chromatin fractionation, HR repair assays, domain mutational analysis Cell reports High 29320735
2018 SCL/TAL1 activates expression of co-repressor ETO2 and Polycomb-PRC1 subunits including RYBP and PCGF5 during blood specification; ETO2 and RYBP co-occupy SCL target genes including cardiac/paraxial loci; reduction of Rybp expression mimics the Scl-null cardiac phenotype, demonstrating SCL-mediated transcriptional repression of alternative fates requires RYBP. Genome-wide ChIP-seq, shRNA knockdown epistasis, single-cell transcriptomics, genetic loss-of-function Nature communications High 30560907
2018 RYBP inhibits polyubiquitination-mediated proteasomal degradation of Ring1B by binding to and promoting ubiquitination/degradation of UBE3A (an E3 ligase that ubiquitinates Ring1B); reduced UBE3A increases Ring1B stability and its H2AK119 monoubiquitination activity. Co-immunoprecipitation, ubiquitination assays, protein stability (half-life) assays, knockdown/overexpression FASEB journal Medium 30040487
2020 RYBP and YAF2 each specifically bind H2AK119ub1 to recruit RYBP-PRC1 or YAF2-PRC1 to catalyze ubiquitination on neighboring nucleosomes via a positive-feedback model; histone H1-compacted chromatin enhances distal propagation of H2AK119ub1; disruption of RYBP/YAF2-PRC1 activity or H1-dependent compaction causes significant defects in H2AK119ub1 maintenance during cell division. In vitro nucleosome binding assays, cell-based propagation assays, H1 knockdown, ChIP, functional genetics Nature cell biology High 32203418
2020 Conditional knockout of Rybp in male germ cells leads to smaller testes, germline cell loss, disturbed meiosis, increased spermatocyte apoptosis, decreased sperm motility, and reduced global H3K9me3, without impacting retrotransposon expression; Rybp deletion during oogenesis had no effect on oocyte maturation or preimplantation development. Conditional knockout mouse model, histology, flow cytometry apoptosis assay, sperm motility assay, H3K9me3 ChIP Cell cycle Medium 32324084
2021 RYBP regulates embryonic neurogenesis through the Notch signaling pathway in a PRC1-independent manner: RYBP deficiency inhibits eNPC proliferation and promotes differentiation; mechanistically, RYBP directly interacts with CIR1, facilitating RBPJ binding to NICD to activate Notch signaling; Rybp loss promotes CIR1 competition with RBPJ for NICD binding, inhibiting Notch; ectopic Hes5 rescues Rybp-deficiency deficits. Rybp conditional KO in neural progenitors, co-immunoprecipitation, ChIP, genetic rescue with Hes5 overexpression Stem cell reports Medium 34798064
2021 RYBP NLS peptide (residues Asn58–Lys83) interacts with importin α3 (Impα3) at its major cargo-binding site with low micromolar affinity; this NLS region is largely unstructured in isolation but mediates nuclear translocation of RYBP. Fluorescence spectroscopy, circular dichroism, isothermal titration calorimetry (ITC), molecular docking Biochimica et biophysica acta. Proteins and proteomics Medium 33945888
2022 RYBP overexpression inhibits ATM kinase activity and ATM recruitment to DNA damage sites, reducing Chk2 phosphorylation; this ATM inhibition sensitizes cancer cells to PARP inhibitors and hinders cancer cell migration. Overexpression studies, kinase activity assays (pChk2 readout), PARP inhibitor sensitivity assays, migration assays International journal of molecular sciences Medium 36233063
2022 In KSHV de novo infection, RYBP binds lytic viral gene promoters in a PRC1-independent manner and represses transcription elongation of the lytic inducer RTA, promoting establishment of KSHV latency; RYBP reduces histone marks associated with transcription elongation without affecting PRC1 activity on the viral genome. shRNA screen, ChIP assays, viral gene expression assays, primary infection model PLoS pathogens Medium 36026503
2023 RYBP-PRC1 binds unmodified nucleosomes via RING1B but switches to binding H2Aub1-modified nucleosomes via RYBP; RYBP interactions with both ubiquitin and the nucleosome acidic patch create high affinity for H2Aub1-modified nucleosomes, enabling RING1B to monoubiquitinate H2A on neighboring unmodified nucleosomes — establishing the structural basis of the H2Aub1 read-write positive feedback loop. Crystal structure/cryo-EM structural determination, biochemical binding assays, mutational analysis Nature structural & molecular biology High 38528151
2023 Rybp knockout impairs mESC neural differentiation by activating Wnt signaling and derepressing non-neuroectoderm-associated genes; Yaf2 knockout promotes neural differentiation and leads to redistribution of RYBP binding and increased H2AK119ub at RYBP-YAF2 co-targeted genes, revealing that RYBP and YAF2 have distinct and opposing functions in neural differentiation. Rybp and Yaf2 knockout mESCs, ChIP-seq, RNA-seq, neural differentiation assays Nature communications High 37935677
2023 RYBP interacts with the citrullinating enzyme PADI4 in the nucleus and cytosol of cancer cells with low micromolar affinity (~1 μM); AlphaFold2-multimer modeling indicates PADI4's catalytic domain interacts with Arg53 of RYBP, suggesting possible citrullination of RYBP; combined PADI4 inhibition and PARP inhibition changes cell proliferation. Immunofluorescence, proximity ligation assay, isothermal titration calorimetry, AlphaFold2-multimer modeling International journal of biological macromolecules Low 37399862
2023 RYBP cooperates with NKX2-5 to transcriptionally activate the P1 and P3 promoters of the Plagl1 gene in a ncPRC1-independent manner; PLAGL1 in turn activates Tnnt2 (important for cardiomyocyte contractility); two non-coding RNAs at the Plagl1 locus also regulate these promoters. Promoter reporter assays, ChIP, transfection in HEK293 and ESCs, Rybp null ESC rescue experiments Open biology Medium 36751888
2024 USP4 deubiquitinates RYBP, preventing its degradation and stabilizing RYBP protein; USP4-mediated RYBP stabilization represses the PI3K/AKT signaling pathway in trophoblast cells, impairing their proliferation, invasion, and migration. Co-immunoprecipitation, deubiquitination assay, western blot, functional trophoblast cell assays, PI3K/AKT pathway readouts Cell biochemistry and biophysics Medium 39405024
2024 RYBP co-localizes with TrxG component WDR5 at super-enhancers in ESCs; RYBP depletion reduces WDR5 and H3K27ac deposition at SEs, decreases SE-associated gene expression and enhancer RNA transcription; RYBP is also required for RING1B enrichment in condensates and selective genomic binding of both TrxG (WDR5) and PcG (RING1B) components; STAT3 excludes RING1B binding at RYBP-associated transcriptionally active loci. ChIP-seq, RNA-seq, HiChIP, RYBP depletion in ESCs, epidermal progenitor and mesodermal cells Molecular medicine (Cambridge, Mass.) / The EMBO journal Medium 39604829 42049912
2024 RYBP co-localizes with mesoderm lineage marker BRACHYURY, and BRACHYURY was identified as a novel binding partner of RYBP; Rybp null ESC gastruloids show shortened tails and low BRACHYURY levels in the tailbud, and mesoderm/endoderm-specific gene expression is disrupted in Rybp null mutants. 3D gastruloid model, co-immunoprecipitation (binding partner identification), immunofluorescence, gene expression analysis Frontiers in cell and developmental biology Medium 39676794
2024 PKP1 armadillo domain binds RYBP with low micromolar affinity (~10 μM) in tumor and non-tumoral cell lines; the interaction occurs in both nucleus and cytoplasm. Immunofluorescence, proximity ligation assay, isothermal titration calorimetry, circular dichroism, in silico docking Biomolecules Low 38785968
2025 YY1 recruits RYBP to the HIV-1 LTR region; RYBP then recruits KDM2B, promoting H2AK119ub and decreasing H3K4me3 at the LTR, thereby reducing HIV-1 transcriptional elongation and establishing latency; viral Tat protein inhibits RYBP expression to promote viral transcription; RYBP KO activates latent HIV-1. enChIP (engineered chromatin immunoprecipitation), gene knockout in latency cell models, ChIP, western blot Cell communication and signaling : CCS Medium 40361117
2025 Heterozygous de novo variants in RYBP (localizing to the N-terminal zinc-finger/ubiquitin-binding domain) cause a syndromic neurodevelopmental disorder; the C44W variant reduces protein expression but does not affect binding to YY1, RING1B, or ubiquitin in vitro; in vivo Drosophila overexpression shows dramatic functional differences between wild-type RYBP and C44-mutant forms. In vitro cellular binding assays (YY1, RING1B, ubiquitin), Drosophila in vivo overexpression, DNA methylation episignature analysis Genetics in medicine Medium 39891528

Source papers

Stage 0 corpus · 81 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 PCGF homologs, CBX proteins, and RYBP define functionally distinct PRC1 family complexes. Molecular cell 702 22325352
2012 RYBP-PRC1 complexes mediate H2A ubiquitylation at polycomb target sites independently of PRC2 and H3K27me3. Cell 462 22325148
1999 RYBP, a new repressor protein that interacts with components of the mammalian Polycomb complex, and with the transcription factor YY1. The EMBO journal 203 10369680
2002 Interaction of YY1 with E2Fs, mediated by RYBP, provides a mechanism for specificity of E2F function. The EMBO journal 175 12411495
2012 RYBP and Cbx7 define specific biological functions of polycomb complexes in mouse embryonic stem cells. Cell reports 169 23273917
1983 Biogenesis of mitochondria: the mitochondrial gene (aap1) coding for mitochondrial ATPase subunit 8 in Saccharomyces cerevisiae. Nucleic acids research 137 6223276
2016 RYBP stimulates PRC1 to shape chromatin-based communication between Polycomb repressive complexes. eLife 119 27705745
2020 RYBP/YAF2-PRC1 complexes and histone H1-dependent chromatin compaction mediate propagation of H2AK119ub1 during cell division. Nature cell biology 93 32203418
2006 The Polycomb-associated protein Rybp is a ubiquitin binding protein. FEBS letters 86 17070805
2005 Rybp/DEDAF is required for early postimplantation and for central nervous system development. Molecular and cellular biology 82 16055728
2012 A novel target of microRNA-29, Ring1 and YY1-binding protein (Rybp), negatively regulates skeletal myogenesis. The Journal of biological chemistry 81 22661705
2012 RYBP represses endogenous retroviruses and preimplantation- and germ line-specific genes in mouse embryonic stem cells. Molecular and cellular biology 75 22269950
2008 RYBP stabilizes p53 by modulating MDM2. EMBO reports 72 19098711
2017 RNA Helicase DDX5 Inhibits Reprogramming to Pluripotency by miRNA-Based Repression of RYBP and its PRC1-Dependent and -Independent Functions. Cell stem cell 62 28111200
2015 YY1 regulates melanoma tumorigenesis through a miR-9 ~ RYBP axis. Journal of experimental & clinical cancer research : CR 55 26104682
2013 Biodegradation of the neonicotinoid insecticide Acetamiprid by bacterium Pigmentiphaga sp. strain AAP-1 isolated from soil. Bioresource technology 53 23624055
2002 YEAF1/RYBP and YAF-2 are functionally distinct members of a cofactor family for the YY1 and E4TF1/hGABP transcription factors. The Journal of biological chemistry 50 11953439
2014 RYBP expression is associated with better survival of patients with hepatocellular carcinoma (HCC) and responsiveness to chemotherapy of HCC cells in vitro and in vivo. Oncotarget 46 25344099
2012 Polymorphisms in RYBP and AOAH genes are associated with chronic rhinosinusitis in a Chinese population: a replication study. PloS one 40 22723975
2009 The transcriptional repressor RYBP is a natively unfolded protein which folds upon binding to DNA. Biochemistry 36 19170609
2018 SCL/TAL1 cooperates with Polycomb RYBP-PRC1 to suppress alternative lineages in blood-fated cells. Nature communications 31 30560907
2010 Molecular mechanism of the interactions between white spot syndrome virus anti-apoptosis protein AAP-1 (WSSV449) and shrimp effector caspase. Developmental and comparative immunology 31 20546774
2007 Rybp, a polycomb complex-associated protein, is required for mouse eye development. BMC developmental biology 27 17470285
2005 The Drosophila RYBP gene functions as a Polycomb-dependent transcriptional repressor. Mechanisms of development 27 16125914
2018 RYBP Is a K63-Ubiquitin-Chain-Binding Protein that Inhibits Homologous Recombination Repair. Cell reports 25 29320735
2008 Adenoviral-mediated Rybp expression promotes tumor cell-specific apoptosis. Cancer gene therapy 25 18551146
1996 Induction of c-Erb A-AP-1 interactions and c-Erb A transcriptional activity in myoblasts by RXR. Consequences for muscle differentiation. The Journal of biological chemistry 25 8626694
2019 MicroRNA-769-5p contributes to the proliferation, migration and invasion of hepatocellular carcinoma cells by attenuating RYBP. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 24 31545279
2017 RYBP Inhibits Progression and Metastasis of Lung Cancer by Suppressing EGFR Signaling and Epithelial-Mesenchymal Transition. Translational oncology 24 28254703
2015 RYBP predicts survival of patients with non-small cell lung cancer and regulates tumor cell growth and the response to chemotherapy. Cancer letters 24 26404750
2016 Proapoptotic RYBP interacts with FANK1 and induces tumor cell apoptosis through the AP-1 signaling pathway. Cellular signalling 23 27060496
2007 Rybp interacts with Hippi and enhances Hippi-mediated apoptosis. Apoptosis : an international journal on programmed cell death 23 17874297
2021 Upregulation of circRNA hsa_circ_0008726 in Pre-eclampsia Inhibits Trophoblast Migration, Invasion, and EMT by Regulating miR-345-3p/RYBP Axis. Reproductive sciences (Thousand Oaks, Calif.) 22 34845670
2015 Lack of Rybp in Mouse Embryonic Stem Cells Impairs Cardiac Differentiation. Stem cells and development 20 26110923
1993 Isolation and characterization of AAP1. A gene encoding an alanine/arginine aminopeptidase in yeast. The Journal of biological chemistry 20 8100228
2020 MiR-769-5p functions as an oncogene by down-regulating RYBP expression in gastric cancer. European review for medical and pharmacological sciences 17 32633360
2024 Structural basis of the histone ubiquitination read-write mechanism of RYBP-PRC1. Nature structural & molecular biology 15 38528151
2021 Concurrent overexpression of amino acid permease AAP1(3a) and SUT1 sucrose transporter in pea resulted in increased seed number and changed cytokinin and protein levels. Functional plant biology : FPB 15 34366001
2016 Tumor suppressor RYBP harbors three nuclear localization signals and its cytoplasm-located mutant exerts more potent anti-cancer activities than corresponding wild type. Cellular signalling 15 27989698
2021 Upregulated miR‑411‑5p levels promote lymph node metastasis by targeting RYBP in head and neck squamous cell carcinoma. International journal of molecular medicine 14 33537835
2016 Expression and clinical significance of PcG-associated protein RYBP in hepatocellular carcinoma. Oncology letters 14 28123534
2021 RYBP modulates embryonic neurogenesis involving the Notch signaling pathway in a PRC1-independent pattern. Stem cell reports 13 34798064
2015 Absence of Rybp Compromises Neural Differentiation of Embryonic Stem Cells. Stem cells international 13 26788067
2020 RYBP inhibits esophageal squamous cell carcinoma proliferation through downregulating CDC6 and CDC45 in G1-S phase transition process. Life sciences 12 32209426
2023 Functional dissection of PRC1 subunits RYBP and YAF2 during neural differentiation of embryonic stem cells. Nature communications 11 37935677
2018 Epigenetic and non-epigenetic functions of the RYBP protein in development and disease. Mechanisms of ageing and development 11 29665352
2018 Overexpression of RYBP inhibits proliferation, invasion, and chemoresistance to cisplatin in anaplastic thyroid cancer cells via the EGFR pathway. Journal of biochemical and molecular toxicology 11 30431689
2015 Role of Polycomb RYBP in Maintaining the B-1-to-B-2 B-Cell Lineage Switch in Adult Hematopoiesis. Molecular and cellular biology 11 26711264
2022 PRC1-independent binding and activity of RYBP on the KSHV genome during de novo infection. PLoS pathogens 10 36026503
2021 The nuclear localization sequence of the epigenetic factor RYBP binds to human importin α3. Biochimica et biophysica acta. Proteins and proteomics 9 33945888
2019 ETS1 targets RYBP transcription to inhibit tumor cell proliferation. Biochemical and biophysical research communications 9 30638661
2023 The intrinsically disordered, epigenetic factor RYBP binds to the citrullinating enzyme PADI4 in cancer cells. International journal of biological macromolecules 8 37399862
2022 Re-expression of circ_0043610 contributes to trophoblast dysfunction through the miR-558/RYBP pathway in preeclampsia. Endocrine journal 8 35908953
2020 RYBP is important for cardiac progenitor cell development and sarcomere formation. PloS one 8 32673370
2023 Deficiency of the Polycomb Protein RYBP and TET Methylcytosine Oxidases Promotes Extensive CpG Island Hypermethylation and Malignant Transformation. Cancer research 7 37272752
2021 Knockdown of miR-125b-5p inhibits the proliferation and invasion of gastric carcinoma cells by targeting RYBP. The Kaohsiung journal of medical sciences 7 34337862
2020 Rybp orchestrates spermatogenesis via regulating meiosis and sperm motility in mice. Cell cycle (Georgetown, Tex.) 7 32324084
2023 Polycomb protein RYBP activates transcription factor Plagl1 during in vitro cardiac differentiation of mouse embryonic stem cells. Open biology 6 36751888
2022 RYBP Sensitizes Cancer Cells to PARP Inhibitors by Regulating ATM Activity. International journal of molecular sciences 6 36233063
2018 Overexpression of the Rybp Gene Inhibits Differentiation of Bovine Myoblasts into Myotubes. International journal of molecular sciences 6 30021933
2016 Construction and analysis of an intergeneric fusion from Pigmentiphaga sp. strain AAP-1 and Pseudomonas sp. CTN-4 for degrading acetamiprid and chlorothalonil. Environmental science and pollution research international 6 27023810
2013 Characterization of the aap1 gene of Agaricus bisporus, a homolog of the yeast YAP1. Comptes rendus biologies 6 24439549
2018 RYBP modulates stability and function of Ring1B through targeting UBE3A. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 5 30040487
2025 De novo variants in RYBP are associated with a severe neurodevelopmental disorder and congenital anomalies. Genetics in medicine : official journal of the American College of Medical Genetics 3 39891528
2025 RYBP promotes HIV-1 latency through promoting H2AK119ub and decreasing H3K4me3. Cell communication and signaling : CCS 3 40361117
2022 RYBP regulates Pax6 during in vitro neural differentiation of mouse embryonic stem cells. Scientific reports 3 35149723
2022 Generation of RYBP FLAG-HA knock-in human embryonic stem cell line through CRISPR/Cas9-mediated homologous recombination. Stem cell research 3 35537243
2024 Brachyury co-operates with polycomb protein RYBP to regulate gastrulation and axial elongation in vitro. Frontiers in cell and developmental biology 2 39676794
2019 Generation of Rybp homozygous knockout murine ES cell line GIBHe001-A-1 by using CRISPR/Cas9 technology. Stem cell research 2 31794887
2025 MicroRNA-770 promotes polarization of macrophages and hemorrhoids by suppressing RYBP expression and monoubiquitination of histone H2A on Lys119 modification. Molecular immunology 1 40174420
2024 Unveiling the Binding between the Armadillo-Repeat Domain of Plakophilin 1 and the Intrinsically Disordered Transcriptional Repressor RYBP. Biomolecules 1 38785968
2024 The Deubiquitinating Enzyme USP4 Promotes Trophoblast Dysfunction by Stabilizing RYBP. Cell biochemistry and biophysics 1 39405024
2024 Polycomb protein RYBP facilitates super-enhancer activity. Molecular medicine (Cambridge, Mass.) 1 39604829
2026 RYBP regulates selective genomic binding of TrxG and PcG components in embryonic stem cell fate control. The EMBO journal 0 42049912
2025 Insulin receptor substrate family member IST-1 regulates the development of Caenorhabditis elegans age-1 and aap-1 mutants. microPublication biology 0 40642152
2025 Genetic Improvement and Functional Characterization of AAP1 Gene for Enhancing Nitrogen Use Efficiency in Maize. Plants (Basel, Switzerland) 0 40733479
2025 Long non-coding RNA RP11-196G11.6 inhibits neuroblastoma progression by regulating the miR-376a-3p/RYBP signaling axis. Oncology letters 0 41246553
2025 A-to-I RNA editing impairs miR-376b-3p repression of RYBP in skeletal muscle satellite cells. The Journal of biological chemistry 0 41354336
2024 Glucose-induced RYBP suppresses tumor cell aerobic glycolysis and migration. Biochemical and biophysical research communications 0 38735205
2019 [Clinical significance of RYBP expression in primary hepatocellular carcinoma]. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 0 31113915
2015 [Effect of RYBP Gene Silencing on Sensitivity of HL-60 Cells to Chemotherapeutic Drugs]. Zhongguo shi yan xue ye xue za zhi 0 26708874

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