Affinage

PRC1

Protein regulator of cytokinesis 1 · UniProt O43663

Length
620 aa
Mass
71.6 kDa
Annotated
2026-06-10
100 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 11/11 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

The PRC1 symbol in this corpus resolves to two distinct, internally coherent proteins. The first, protein regulator of cytokinesis 1, is a conserved microtubule-associated protein required for cytokinesis: antibody microinjection blocks cellular cleavage without affecting nuclear division (PMID:9885575), and the protein directly binds and bundles antiparallel microtubules through its central conserved region while its N-terminus directs cleavage-furrow and midbody localization (PMID:12082078). Its bundling activity is held off during early mitosis by CDK phosphorylation, since a phospho-null mutant causes ectopic prometaphase bundling (PMID:12082078), and is further restrained by direct p27Kip1 binding that blocks microtubule association without disrupting dimerization (PMID:30327204); additional kinase input comes from CDK16 (PMID:35449080) and the Aurora pathway in yeast orthologs (PMID:17765685). PRC1 depletion abolishes interdigitation of half-spindles and eliminates the midzone (PMID:12082078), and during anaphase PRC1 binds compacting overlaps with progressively slower turnover, consistent with a bundling-sliding-compaction model (PMID:34580180). It acts as a midzone scaffold that recruits KIF4A through a conserved hydrophobic motif also used by CENP-E, which slides PRC1-crosslinked microtubules to control chromosome partitioning and central spindle integrity (PMID:23870126, PMID:37592895); it likewise bridges sister kinetochore fibers to balance metaphase forces (PMID:28028032). The yeast ortholog Ase1 establishes the conserved role: it is degraded by the APC/C at mitotic exit to permit spindle disassembly (PMID:9036857), drives dose-dependent bundling, and supports kinesin-5-independent bipolar spindle assembly by recruiting CLASP (PMID:15647375, PMID:28513584). The second, entirely separate protein is the Polycomb repressive complex 1 (RING1/RNF2-PCGF-BMI1 catalytic core), which monoubiquitylates histone H2AK119 to drive Polycomb domain formation and gene repression (PMID:31883950, PMID:27827373). PRC1 represses transcription by counteracting RNA polymerase II recruitment and controlling transcriptional burst frequency (PMID:34608337), blocking preinitiation-complex assembly by evicting Mediator while sparing TFIID/TBP in vitro (PMID:22910904). Variant PRC1 complexes are targeted to chromatin by DNA-binding subunits (e.g., KDM2B) independently of catalysis and are the primary drivers of repressive H2AK119ub, whereas canonical PRC1 is recruited via CBX reading of PRC2-deposited H3K27me3 and mediates long-range chromatin interactions independently of its enzymatic activity (PMID:31883950, PMID:31029541, PMID:32439634, PMID:37030288). H2AK119ub is read by RYBP/YAF2 to propagate the mark through a positive-feedback loop (PMID:32203418), and PRC1 nucleates phase-separated condensates whose initiation, morphology, and dynamics are tuned by CBX and PHC subunit identity and PHC polymerization (PMID:39815045, PMID:38521066). In vivo, PRC1 is recruited to the inactive X via Xist/hnRNPK-PCGF3/5 to initiate chromosome-wide silencing and S1/S2 compartmentalization (PMID:29220657, PMID:28596365, PMID:31270318), targets pericentric heterochromatin via CBX2 to direct DAXX-mediated H3.3 deposition and chromosome stability (PMID:25801166, PMID:32395866), and maintains neuronal Hox repression and chromatin topology even without de novo PRC2 methylation (PMID:34994686). The cytokinesis PRC1 is therapeutically relevant in Ewing sarcoma, where EWSR1-FLI1 drives its enhancer-mediated overexpression and creates a PLK1-inhibition vulnerability (PMID:34531368).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1997 High

    Establishing that the yeast ortholog Ase1 is a cell-cycle-regulated spindle factor created the framework for a conserved midzone protein controlled by proteolysis.

    Evidence APC/C-dependent degradation, non-degradable mutant, and loss-of-function analysis of spindle stability in S. cerevisiae

    PMID:9036857

    Open questions at the time
    • Did not establish direct microtubule bundling biochemistry
    • Mammalian ortholog role not yet defined
  2. 1998 High

    Identifying PRC1 as a CDK substrate functionally required for cytokinesis defined it as a cell-cycle-regulated cleavage factor distinct from nuclear division.

    Evidence In vitro CDK kinase assay, in vivo phosphorylation, and antibody microinjection in human cells

    PMID:9885575

    Open questions at the time
    • Direct microtubule activity not yet shown
    • Which CDK phosphosites matter functionally not mapped
  3. 2002 High

    Demonstrating direct microtubule bundling, domain requirements, and CDK suppression of bundling explained how PRC1 builds the midzone and why it is held off until anaphase.

    Evidence In vitro bundling assay, truncation and CDK phospho-null mutants, siRNA knockdown in human cells

    PMID:12082078

    Open questions at the time
    • Did not resolve how bundling activity is reactivated at anaphase onset
    • Midzone partner recruitment not yet mapped
  4. 2007 High

    Linking Ase1 to Aurora/Ipl1 kinase in spindle assembly connected midzone bundling to mitotic kinase regulation in a motor-independent pathway.

    Evidence Genetic epistasis, overexpression rescue, and phosphosite mutagenesis in S. cerevisiae

    PMID:17765685

    Open questions at the time
    • Mammalian Aurora regulation of PRC1 not directly addressed here
  5. 2013 High

    The PRC1 crystal structure plus reconstitution of length-dependent plus-end tagging with KIF4A revealed how PRC1 recruits a kinesin to mark and size microtubule overlaps.

    Evidence Crystal structure, in vitro reconstitution, interaction mapping, and live-cell imaging

    PMID:23870126

    Open questions at the time
    • Did not resolve full midzone interactome
    • Regulation of tagging in vivo incomplete
  6. 2016 High

    Showing PRC1 bundles bridge sister kinetochore fibers extended its role from the midzone to metaphase spindle force balance.

    Evidence Endogenous PRC1-GFP live imaging and siRNA knockdown with interkinetochore distance readout in human cells

    PMID:28028032

    Open questions at the time
    • Mechanism coupling bridging fibers to k-fiber tension not fully resolved
  7. 2018 Medium

    Identifying p27Kip1 as a direct inhibitor of PRC1 microtubule binding added a non-CDK brake on bundling relevant to ploidy control.

    Evidence Co-IP, in vitro bundling assay, and overexpression multinucleation rescue in human cells

    PMID:30327204

    Open questions at the time
    • Physiological window of p27-PRC1 regulation in normal cycling cells unclear
    • Single-lab biochemistry
  8. 2023 High

    Demonstrating CENP-E binds PRC1 via the same motif as KIF4A and slides crosslinked microtubules clarified how multiple motors are spatiotemporally coordinated on the PRC1 scaffold.

    Evidence Structural analysis, in vitro microtubule sliding reconstitution, and cell-based knockdown

    PMID:37592895

    Open questions at the time
    • Competition/handoff between KIF4A and CENP-E on PRC1 not fully quantified
  9. 2012 High

    Reconstituting that Polycomb PRC1 blocks RNA Pol II preinitiation by evicting Mediator but not TFIID defined the biochemical mechanism of PRC1 transcriptional repression.

    Evidence In vitro transcription and PIC assembly on H3K27-methylated chromatin templates with purified components

    PMID:22910904

    Open questions at the time
    • In vivo relevance of Mediator eviction across loci not addressed here
  10. 2017 High

    Mapping Xist/hnRNPK-PCGF3/5-PRC1 recruitment and the epistatic ordering of PRC1 before PRC2 established how non-canonical PRC1 initiates X-chromosome silencing.

    Evidence Deletion mapping, synthetic tethering, ChIP-seq, and Pcgf3/5 knockout developmental assays in mouse cells

    PMID:28596365 PMID:29220657

    Open questions at the time
    • How H2AK119ub signals PRC2 recruitment mechanistically remains incomplete
  11. 2019 High

    Combinatorial genetics and catalytic-dead mutants separated variant PRC1 (repressive H2A ubiquitylation) from canonical PRC1 (3D chromatin architecture), resolving the division of labor within Polycomb.

    Evidence Conditional catalytic mutation, combinatorial subunit knockouts, ChIP-seq, Hi-C, RNA-seq in mouse ESCs

    PMID:31029541 PMID:31036804 PMID:31883950

    Open questions at the time
    • Quantitative contribution of each variant subcomplex at individual loci not fully parsed
  12. 2020 High

    Defining RYBP/YAF2 reading of H2AK119ub and the catalysis-independence of long-range interactions explained mark propagation and the separability of compaction from enzymatic activity.

    Evidence Reconstituted feedback ubiquitination, binding assays, catalytic mutant Hi-C, and H1 compaction assays

    PMID:32203418 PMID:32439634

    Open questions at the time
    • Molecular basis of catalysis-independent bridging not structurally resolved
  13. 2021 High

    Rapid degron depletion with single-cell analysis showed PRC1 controls transcriptional burst frequency uniformly, refining the mechanism of repression beyond steady-state averages.

    Evidence Auxin-inducible degron, time-resolved ChIP-seq/RNA-seq, single-cell gene expression

    PMID:34608337

    Open questions at the time
    • Link between burst-frequency control and chromatin condensation not directly tested
  14. 2024 High

    Structural and reconstitution studies of PRC1 condensates revealed how CBX and PHC subunit identity tune condensate properties and chromatin accessibility, mechanistically grounding Polycomb compaction.

    Evidence Cryo-electron tomography, in vitro reconstitution, single-molecule and live-cell imaging in mouse ESCs

    PMID:38521066 PMID:39815045

    Open questions at the time
    • How condensate properties translate to gene-specific repression in vivo remains open

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the two unrelated PRC1 proteins (the cytokinesis microtubule bundler and the Polycomb H2A ubiquitin ligase) are disambiguated in shared literature and whether any regulatory crosstalk exists between cell-cycle and chromatin functions.
  • No timeline finding links the two proteins mechanistically
  • Symbol collision must be tracked carefully in downstream interpretation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0016874 ligase activity 3 GO:0042393 histone binding 3 GO:0060090 molecular adaptor activity 3 GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005856 cytoskeleton 3 GO:0005654 nucleoplasm 2 GO:0005634 nucleus 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-4839726 Chromatin organization 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
BMI1CBX2CENP-EHNRNPKKIF4AP27KIP1PHC2RYBP
Complex memberships
Polycomb repressive complex 1 (canonical, RING1/RNF2-PCGF-CBX-PHC-BMI1)Variant PRC1 (RING1/RNF2-PCGF-RYBP/YAF2; PCGF3/5-PRC1; KDM2B-PRC1)central spindle / midzone microtubule bundle

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 PRC1 (protein regulator of cytokinesis 1) is a substrate for several CDKs in vitro and is phosphorylated in vivo at CDK consensus sites; it is a nuclear protein in interphase that associates with mitotic spindles dynamically and localizes to the midbody during cytokinesis. Microinjection of anti-PRC1 antibodies blocked cellular cleavage but not nuclear division, establishing a direct functional requirement for PRC1 in cytokinesis. In vitro CDK phosphorylation assay, in vivo phosphorylation analysis, immunofluorescence, antibody microinjection Molecular cell High 9885575
2002 PRC1 directly binds and bundles microtubules both in vivo and in vitro. The central region (highest interspecies homology) is required for microtubule binding and bundling; the N-terminal alpha-helical region is required for localization to the cleavage furrow and midbody center. CDK phosphorylation of PRC1 suppresses its bundling activity during mitosis, as a CDK phosphorylation-null mutant causes extensive bundling of the prometaphase spindle. siRNA depletion of PRC1 abolishes microtubule interdigitation between half-spindles and eliminates the spindle midzone. In vitro microtubule bundling assay, overexpression/truncation mutant analysis, CDK phosphorylation-null mutagenesis, siRNA knockdown, immunofluorescence The Journal of cell biology High 12082078
1997 Yeast Ase1 (ortholog of PRC1) undergoes APC/cyclosome-mediated proteolysis when cells exit mitosis and enter G1. Stable (non-degradable) Ase1 expression in G1 produces a spindle defect sensed by the spindle assembly checkpoint, and loss of ASE1 function destabilizes telophase spindles, while a nondegradable mutant delays spindle disassembly. Genetic analysis, cell cycle synchronization, protein stability assays, spindle checkpoint analysis in S. cerevisiae Science (New York, N.Y.) High 9036857
2005 Fission yeast Ase1 localizes to microtubule overlapping zones and is a dose-dependent microtubule-bundling factor: deletion impairs bundling while overproduction causes excessive bundling in an opposing manner. Ase1 is required for Aurora kinase (correct localization to central spindles), spindle stability in anaphase B, nuclear/septum positioning, cytokinesis completion, and acts as a regulatory component of the cytokinesis checkpoint that inhibits nuclear division when cytokinesis is perturbed. Gene deletion, overexpression, time-lapse imaging, immunofluorescence in S. pombe Molecular biology of the cell High 15647375
2007 Budding yeast Ipl1/Aurora kinase and Ase1 define a spindle assembly pathway: Ase1 is required for bipolar spindle assembly in the absence of BimC motor Cin8; Ase1 overexpression rescues spindle assembly defects in cin8 ipl1 double mutants; an ase1 mutant lacking Ipl1 consensus phosphorylation sites cannot assemble spindles without Cin8; and Ase1 phosphorylation and localization are altered in ipl1 mutants. Genetic epistasis (double mutants), overexpression rescue, phosphorylation site mutagenesis, immunofluorescence in S. cerevisiae Developmental cell High 17765685
2013 PRC1 and kinesin-4 (KIF4A) can tag microtubule plus ends in vitro, with tag size proportional to filament length. Crystal structure of the PRC1 homodimer was determined and protein-protein interactions required for microtubule end tagging were mapped. Length-dependent microtubule plus-end tagging by PRC1 was also observed in dividing cells. In vitro reconstitution, crystal structure determination, protein-protein interaction mapping, live-cell imaging Cell High 23870126
2016 PRC1-GFP-labeled bundles in the mitotic spindle show one-to-one association with kinetochore pairs (bridging fiber), acting as a bridge between sister kinetochore fibers. PRC1 knockdown reduces bridging fiber thickness and interkinetochore distance throughout the spindle, demonstrating a function in bridging microtubule organization and force balance in the metaphase spindle. Live-cell imaging (PRC1-GFP), siRNA knockdown, quantitative analysis of kinetochore movements, endogenous PRC1 localization EMBO reports High 28028032
2018 p27Kip1 binds directly to PRC1 and interferes with PRC1's ability to bind microtubules without affecting PRC1 dimerization or its interaction with KIF4. p27 inhibits microtubule bundling by PRC1 in vitro and prevents extensive microtubule bundling caused by PRC1 overexpression in cells; co-expression of p27 inhibits multinucleation induced by PRC1 overexpression. Co-immunoprecipitation, in vitro microtubule bundling assay, overexpression in cells, domain mapping Biochimica et biophysica acta. Molecular cell research Medium 30327204
2020 In mouse oocyte meiosis, PRC1 accumulates at the spindle midzone/midbody during anaphase/telophase I. PRC1 knockdown prevents formation of the midzone and midbody, causing cytokinesis failure and formation of two spindles; microtubule acetylation is increased upon PRC1 depletion. KIF4A and PRC1 co-localize at the midzone/midbody, and KIF4A depletion affects PRC1 expression and localization. siRNA knockdown in mouse oocytes, immunofluorescence, mRNA rescue injection The FEBS journal Medium 33206458
2022 CDK16 phosphorylates PRC1 to regulate spindle formation during mitosis in triple-negative breast cancer cells. CDK16 depletion impairs PRC1-dependent spindle regulation. Kinase assay, transcriptome profiling, co-immunoprecipitation, in vitro and in vivo tumor models Journal of experimental & clinical cancer research : CR Medium 35449080
2023 Human CENP-E motor binds to PRC1 through a conserved hydrophobic motif (the same binding mechanism used by Kinesin-4 KIF4A). In vitro reconstitution shows CENP-E slides antiparallel PRC1-crosslinked microtubules. CENP-E–PRC1 interaction is spatially and temporally regulated: it is required in anaphase to control chromosome partitioning, maintain central spindle integrity, and ensure cytokinesis. Structural biology, in vitro microtubule reconstitution, cell biology (live imaging, knockdown), interaction mapping The EMBO journal High 37592895
2020 In human cells expressing endogenous fluorescent PRC1, PRC1 binds increasingly strongly to compacting antiparallel microtubule overlaps during anaphase, progressively decreasing its turnover. The central spindle gradually becomes more stable during mitosis consistent with a 'bundling, sliding, and compaction' model. CRISPR gene editing (endogenous fluorescent tagging), live-cell imaging, FRAP Life science alliance Medium 34580180
2020 During replication stress in budding yeast, the S phase checkpoint activates intragenic transcription of ASE1, producing short Ase1 isoforms that localize to the spindle and antagonize full-length Ase1 midzone localization, thereby stabilizing the spindle. Blocking generation of short isoforms destabilizes the S phase spindle. Molecular genetics (checkpoint mutants, intragenic transcript analysis), live-cell imaging, overexpression of short isoforms Current biology : CB Medium 24768052
2020 In budding yeast, Ase1's spectrin domain uses conserved basic residues to promote midzone recruitment before anaphase onset and slows spindle elongation during early anaphase. The carboxy-terminal domain is required for stable midzone formation in late anaphase and physically interacts with EB1/Bim1 to recruit it to the midzone, maintaining midzone length. Domain deletion/mutagenesis, live-cell imaging, protein interaction assays in S. cerevisiae Molecular biology of the cell Medium 32997572
2017 In fission yeast, Kinesin-5-independent bipolar spindle assembly requires the microtubule antiparallel bundler PRC1/Ase1, which recruits CLASP/Cls1 to stabilize microtubules. Brownian dynamics simulations confirm that Ase1 and Cls1 activity are sufficient for initial bipolar spindle formation via microtubule polymerization-driven pole separation. Genetic epistasis (double/triple mutants), live-cell imaging, Brownian dynamics simulations in S. pombe Nature communications Medium 28513584
2019 In fission yeast, Kinesin-6/Klp9 interacts functionally with Ase1 for spindle integrity: klp9Δase1Δ double deletion is synthetically lethal, and this lethality depends on the non-motor region (NLS and coiled-coil) of Klp9 rather than its motor activity, indicating Ase1 and non-motor Klp9 cooperate in maintaining structural integrity of spindle microtubules. Genetic epistasis (synthetic lethality), domain deletion analysis, TIRF microscopy in S. pombe Scientific reports Medium 31089172
2021 PRC1 (Polycomb repressive complex 1) functions independently of PRC2 to counteract RNA polymerase II binding and transcription initiation. Using rapid degron-based depletion and single-cell gene expression analysis, PRC1 was shown to act uniformly within the cell population to control transcriptional burst frequency as the mechanism of gene repression. Auxin-inducible degron system, time-resolved genomics (ChIP-seq, RNA-seq), single-cell gene expression analysis Nature structural & molecular biology High 34608337
2012 Recombinant PRC1 (Polycomb repressive complex 1) inhibits transcription by blocking assembly of RNA polymerase II preinitiation complexes (PICs) on H3K27-methylated chromatin templates in vitro: PRC1 blocks recruitment of Mediator but not TFIID/TBP, thereby dissociating PICs. In vitro transcription on immobilized chromatin templates, PIC assembly assays with purified components, ChIP-seq reanalysis The Journal of biological chemistry High 22910904
2019 PRC1 catalytic activity (RING1B-mediated H2AK119 monoubiquitylation) drives Polycomb chromatin domain formation and long-range chromatin interactions. Variant PRC1 complexes with DNA-binding activities (e.g., KDM2B-PRC1) occupy target sites independently of PRC1 catalytic activity, providing a mechanism for target site selection. Polycomb-mediated gene repression requires PRC1 catalytic activity. Conditional catalytic-dead mutation in ESCs (RING1B mutation), ChIP-seq, Hi-C, RNA-seq Molecular cell High 31883950
2016 Cbx7 is targeted to chromatin by co-recognition of H3K27me3 (via chromodomain) and DNA (via AT-hook-like motif), which together constitute a functional DNA-binding unit within PRC1. Disruption of PRC1 complex formation facilitates Cbx7 chromatin targeting. H3K27me3 contributes significantly to Cbx7 and Cbx8 chromatin targeting but less so for Cbx2, Cbx4, and Cbx6. Live-cell single-molecule tracking, genetic engineering (endogenous tagging/knockout), biochemical analyses (chromodomain and ATL motif mutants) eLife High 27723458
2015 Cbx2 directs catalytically active PRC1 to paternal pericentric heterochromatin (PCH) via its chromodomain (binding H3K27me3) and neighboring AT-hook motif (binding AT-rich major satellites). HP1β (not H3K9me3) prevents PRC1 targeting to maternal PCH by blocking the Cbx2 AT-hook from interacting with DNA at H3K9me3/HP1β-marked PCH. Loss-of-function studies (Hp1β KO, H3K9me3 depletion), domain mutagenesis, immunofluorescence in mouse early embryos Molecular cell High 25801166
2016 BMI1 (a PRC1 core component) homo-oligomerizes via its ubiquitin-like (UBL) central domain and binds polyhomeotic protein PHC2 in a β-hairpin conformation (crystal structure). Both BMI1-PHC2 interaction and BMI1 homo-oligomerization via the UBL domain are necessary for H2A ubiquitination activity of PRC1 and for clonogenic potential. Crystal structure determination, NMR spectroscopy, Co-IP, H2A ubiquitination assay, clonogenic assay Nature communications High 27827373
2020 RYBP and YAF2 each specifically bind H2AK119ub1 to recruit their respective RYBP-PRC1 or YAF2-PRC1 complex to catalyze H2A ubiquitination on neighboring nucleosomes through 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 loss of H2AK119ub1 maintenance during cell division. Biochemical binding assays, H2A ubiquitination assays, chromatin compaction assays, H1 depletion Nature cell biology High 32203418
2017 hnRNPK recruits PCGF3/5-PRC1 to the Xist RNA B-repeat element (XR-PID) to initiate Polycomb-mediated chromosomal silencing. Deletion of XR-PID abolishes Polycomb recruitment and Xist-mediated gene silencing; synthetic tethering of hnRNPK to Xist lacking XR-PID is sufficient for Polycomb recruitment. Deletion mapping, RNA pulldown, synthetic tethering assay, ChIP-seq, gene expression analysis Molecular cell High 29220657
2017 PCGF3/5-PRC1 complex initiates recruitment of both PRC1 and PRC2 in response to Xist RNA. PCGF3/5-PRC1-mediated H2AK119 ubiquitylation signals recruitment of other non-canonical PRC1 complexes and PRC2, which deposits H3K27me3 chromosome-wide. Pcgf3/5 double knockout results in female-specific embryo lethality and abrogates Xist-mediated gene repression. Gene knockout (Pcgf3/5 KO), ChIP-seq, RNA-seq, X-inactivation assays Science (New York, N.Y.) High 28596365
2020 PRC1 drives formation of Xi S1/S2 compartments via Xist RNA recruitment. Loss of SMCHD1 traps Xist in the S1 compartment, impairing RNA spreading to S2. Depletion of Xist, PRC1, or HNRNPK precludes re-emergence of S1/S2 compartments; loss of S1/S2 paradoxically strengthens partition between Xi megadomains. PRC1 and SMCHD1 act sequentially to partition, fuse, and direct Xi compartment self-association. Conditional depletion (Xist, PRC1, HNRNPK, SMCHD1), Hi-C, super-resolution imaging Nature communications Medium 31270318
2019 Canonical PRC1 (cPRC1), but not variant PRC1, maintains gene silencing through cell division after removal of tethering. Propagation of gene repression is sustained by cis-acting histone modifications (H3K27me3 by PRC2 and H2AK119ub1 by cPRC1), promoting a sequence-independent positive-feedback mechanism for PcG protein recruitment. Reversible tethering of PcG proteins to ectopic sites, epigenetic analysis (ChIP-seq), cell division tracking in mouse ESCs Nature communications Medium 31036804
2019 Variant PRC1 complexes are the primary drivers of H2A monoubiquitylation associated with Polycomb target gene repression and X chromosome inactivation; canonical PRC1 (which mediates higher-order chromatin structures) contributes little to gene repression. Synergy between variant PRC1 complexes is fundamental to gene repression. Combinatorial genetic perturbation (multiple subunit knockouts), quantitative genomics (ChIP-seq, RNA-seq) in mouse ESCs Molecular cell High 31029541
2020 SUMOylated CBX2-containing PRC1 recruits the H3.3-specific chaperone DAXX to paternal pericentric heterochromatin (pat-PCH). Loss of Daxx or PRC1 components Ring1/Rnf2 abrogates H3.3 incorporation, induces chromatin decompaction and breakage at pat-PCH, and causes paternal chromosome mis-segregation. DAXX-mediated H3.3 deposition is required for chromosome stability in early embryos. Protein interaction assays (SUMO pulldown, Co-IP), genetic knockout (Daxx, Ring1, Rnf2), immunofluorescence, complementation assays in mouse embryos The EMBO journal High 32395866
2020 Canonical PRC1 (cPRC1) impairment of enzymatic activity does not directly disrupt PRC1-mediated long-range chromatin interactions (as determined by Hi-C), indicating that chromatin compaction by cPRC1 is independent of its catalytic H2A ubiquitylation activity. PRC1-mediated long-range interactions are independent of CTCF and can bridge sites at megabase scale. Catalytic mutant cell lines, Hi-C, imaging, ChIP-seq in mouse ESCs Genes & development High 32439634
2024 PRC1-condensed chromatin (solved by cryo-electron tomography) adopts a porous structure stabilized by multivalent dynamic interactions. Positively charged residues on CBX8's internally disordered regions mask negative charges on DNA to stabilize the condensed chromatin state. Within condensates, PRC1 remains dynamic while maintaining a static chromatin structure; CBX8-bound chromatin remains accessible in differentiated cells. Cryo-electron tomography, live-cell imaging, domain mutagenesis, chromatin accessibility assays Nature structural & molecular biology High 39815045
2021 PRC1 in live mouse ESCs is highly dynamic with only a small fraction stably interacting with chromatin. PRC1 exhibits low occupancy at target sites. Specific subunit identities (CBX and PHC proteins) define PRC1 kinetics and chromatin binding dynamics. Single particle tracking (SPT) in live cells, genome engineering (endogenous tagging), chromatin binding perturbation Nature communications Medium 33563969
2024 PRC1 modularity (specific PHC and CBX subunit combinations) determines condensate initiation, morphology, stability, and dynamics. PHC2's polymerization activity promotes formation of distinct domains that adhere but do not coalesce. Nucleosomal arrays and PRC1 act synergistically to reduce the critical concentration for condensation more than 20-fold. In vitro reconstitution, single-molecule imaging, live-cell imaging in mouse ESCs Molecular cell High 38521066
2023 PRC2.1 catalyzes the majority of H3K27me3 and recruits CBX2/4-cPRC1 but not CBX7-cPRC1. JARID2 (a PRC2.2-specific accessory protein) is essential for recruitment of CBX7-cPRC1 and consequent 3D chromatin interactions at Polycomb target genes. Genetic knockout and replacement of PRC2 subcomplex-specific subunits, ChIP-seq, Hi-C in pluripotent cells Molecular cell High 37030288
2020 PRC1 loss in Ring1 mutant mice leads to increased chromatin accessibility and ectopic expression of Hox transcription factors (including Hox13 paralogs) in postmitotic spinal motor neurons, while PRC2 activity is dispensable for maintaining motor neuron positional identity. Derepressed Hox13 paralogs suppress Hox-dependent specification programs, causing loss of MN subtype identity. PRC1 can function independently of de novo PRC2-dependent histone methylation to maintain chromatin topology. Conditional Ring1 knockout in mice, ATAC-seq, RNA-seq, genetic epistasis eLife High 34994686
2019 BAP1 (H2A deubiquitinase) decreases H2Aub at the SLC7A11 promoter while PRC1 increases H2Aub binding there; however, both BAP1 and PRC1 repress SLC7A11 expression, indicating dynamic regulation of H2Aub—not a simple activating role for PRC1 H2A ubiquitination at this locus. ChIP, gene knockdown/overexpression, reporter assays Cell cycle (Georgetown, Tex.) Medium 30907299
2022 PRC1 (protein regulator of cytokinesis 1) is overexpressed in EwS due to EWSR1-FLI1 binding a proximal GGAA-microsatellite enhancer. High PRC1 creates vulnerability to PLK1 inhibition by causing mitotic catastrophe when cytokinesis is uncoupled from mitosis. CRISPR-mediated enhancer editing confirms enhancer-driven PRC1 overexpression. CRISPR enhancer editing, transcriptome profiling, in vitro and in vivo functional experiments (xenograft, PLK1 inhibition) Nature communications Medium 34531368

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 PRC1 is a microtubule binding and bundling protein essential to maintain the mitotic spindle midzone. The Journal of cell biology 369 12082078
1998 PRC1: a human mitotic spindle-associated CDK substrate protein required for cytokinesis. Molecular cell 311 9885575
2017 hnRNPK Recruits PCGF3/5-PRC1 to the Xist RNA B-Repeat to Establish Polycomb-Mediated Chromosomal Silencing. Molecular cell 264 29220657
1997 APC-mediated proteolysis of Ase1 and the morphogenesis of the mitotic spindle. Science (New York, N.Y.) 226 9036857
2017 PCGF3/5-PRC1 initiates Polycomb recruitment in X chromosome inactivation. Science (New York, N.Y.) 214 28596365
2019 Synergy between Variant PRC1 Complexes Defines Polycomb-Mediated Gene Repression. Molecular cell 211 31029541
2019 PRC1 Catalytic Activity Is Central to Polycomb System Function. Molecular cell 207 31883950
2004 In vivo dynamics and differential microtubule-binding activities of MAP65 proteins. Plant physiology 141 15557096
2005 The roles of fission yeast ase1 in mitotic cell division, meiotic nuclear oscillation, and cytokinesis checkpoint signaling. Molecular biology of the cell 130 15647375
2013 Marking and measuring single microtubules by PRC1 and kinesin-4. Cell 127 23870126
2014 PRC1 complex diversity: where is it taking us? Trends in cell biology 125 25065329
2019 Regulation of H2A ubiquitination and SLC7A11 expression by BAP1 and PRC1. Cell cycle (Georgetown, Tex.) 119 30907299
2020 A central role for canonical PRC1 in shaping the 3D nuclear landscape. Genes & development 110 32439634
2018 The SS18-SSX Oncoprotein Hijacks KDM2B-PRC1.1 to Drive Synovial Sarcoma. Cancer cell 109 29502955
2018 PRC1 Fine-tunes Gene Repression and Activation to Safeguard Skin Development and Stem Cell Specification. Cell stem cell 106 29727681
2016 Live-cell single-molecule tracking reveals co-recognition of H3K27me3 and DNA targets polycomb Cbx7-PRC1 to chromatin. eLife 97 27723458
2020 RYBP/YAF2-PRC1 complexes and histone H1-dependent chromatin compaction mediate propagation of H2AK119ub1 during cell division. Nature cell biology 93 32203418
2017 Demethylated HSATII DNA and HSATII RNA Foci Sequester PRC1 and MeCP2 into Cancer-Specific Nuclear Bodies. Cell reports 84 28329686
2021 PRC1 drives Polycomb-mediated gene repression by controlling transcription initiation and burst frequency. Nature structural & molecular biology 83 34608337
2018 A Non-canonical BCOR-PRC1.1 Complex Represses Differentiation Programs in Human ESCs. Cell stem cell 83 29337181
2016 Interdependence of PRC1 and PRC2 for recruitment to Polycomb Response Elements. Nucleic acids research 82 27557709
2015 Cbx2 targets PRC1 to constitutive heterochromatin in mouse zygotes in a parent-of-origin-dependent manner. Molecular cell 75 25801166
2017 Polycomb complexes PRC1 and their function in hematopoiesis. Experimental hematology 73 28087428
2019 PRC1 collaborates with SMCHD1 to fold the X-chromosome and spread Xist RNA between chromosome compartments. Nature communications 68 31270318
2017 Kinesin-5-independent mitotic spindle assembly requires the antiparallel microtubule crosslinker Ase1 in fission yeast. Nature communications 64 28513584
2020 Mammalian PRC1 Complexes: Compositional Complexity and Diverse Molecular Mechanisms. International journal of molecular sciences 63 33202645
2016 PRC1-labeled microtubule bundles and kinetochore pairs show one-to-one association in metaphase. EMBO reports 63 28028032
2021 Live-cell single particle tracking of PRC1 reveals a highly dynamic system with low target site occupancy. Nature communications 61 33563969
2019 Canonical PRC1 controls sequence-independent propagation of Polycomb-mediated gene silencing. Nature communications 60 31036804
2013 The polycomb complex PRC1: composition and function in plants. Journal of genetics and genomics = Yi chuan xue bao 59 23706298
2007 A pathway containing the Ipl1/aurora protein kinase and the spindle midzone protein Ase1 regulates yeast spindle assembly. Developmental cell 59 17765685
2023 PRC2.1- and PRC2.2-specific accessory proteins drive recruitment of different forms of canonical PRC1. Molecular cell 58 37030288
2015 PRC1 is taking the lead in PcG repression. The Plant journal : for cell and molecular biology 58 25754661
2012 Polycomb repressive complex 1 (PRC1) disassembles RNA polymerase II preinitiation complexes. The Journal of biological chemistry 58 22910904
2017 PRC1: Linking Cytokinesis, Chromosomal Instability, and Cancer Evolution. Trends in cancer 57 29413422
2016 BMI1 regulates PRC1 architecture and activity through homo- and hetero-oligomerization. Nature communications 57 27827373
2012 Polycomb in stem cells: PRC1 branches out. Cell stem cell 54 22770239
2020 Activity of PRC1 and Histone H2AK119 Monoubiquitination: Revising Popular Misconceptions. BioEssays : news and reviews in molecular, cellular and developmental biology 50 32196702
2013 Nonredundant and locus-specific gene repression functions of PRC1 paralog family members in human hematopoietic stem/progenitor cells. Blood 50 23349393
2006 MAP65: a bridge linking a MAP kinase to microtubule turnover. Current opinion in plant biology 49 17011227
2021 Repression of germline genes by PRC1.6 and SETDB1 in the early embryo precedes DNA methylation-mediated silencing. Nature communications 46 34857746
2017 Samd7 is a cell type-specific PRC1 component essential for establishing retinal rod photoreceptor identity. Proceedings of the National Academy of Sciences of the United States of America 45 28900001
2006 The role of MAP65-1 in microtubule bundling during Zinnia tracheary element formation. Journal of cell science 45 16449317
2019 Chromatin folding and nuclear architecture: PRC1 function in 3D. Current opinion in genetics & development 41 31323466
2012 End-binding proteins and Ase1/PRC1 define local functionality of structurally distinct parts of the microtubule cytoskeleton. Trends in cell biology 40 23103209
2022 CDK16 promotes the progression and metastasis of triple-negative breast cancer by phosphorylating PRC1. Journal of experimental & clinical cancer research : CR 39 35449080
2018 Dual localized kinesin-12 POK2 plays multiple roles during cell division and interacts with MAP65-3. EMBO reports 39 30002118
2012 A PLETHORA-auxin transcription module controls cell division plane rotation through MAP65 and CLASP. Cell 39 22500804
2022 BCOR and BCORL1 Mutations Drive Epigenetic Reprogramming and Oncogenic Signaling by Unlinking PRC1.1 from Target Genes. Blood cancer discovery 38 35015684
2018 PRC1 preserves epidermal tissue integrity independently of PRC2. Genes & development 36 30567998
2013 MAP65-1a positively regulates H2O2 amplification and enhances brassinosteroid-induced antioxidant defence in maize. Journal of experimental botany 36 23956414
2017 Kdm2b Regulates Somatic Reprogramming through Variant PRC1 Complex-Dependent Function. Cell reports 33 29166607
2021 Variant PCGF1-PRC1 links PRC2 recruitment with differentiation-associated transcriptional inactivation at target genes. Nature communications 32 34504070
2018 SCL/TAL1 cooperates with Polycomb RYBP-PRC1 to suppress alternative lineages in blood-fated cells. Nature communications 31 30560907
2019 Mechanisms of the Ase1/PRC1/MAP65 family in central spindle assembly. Biological reviews of the Cambridge Philosophical Society 30 31343816
2024 Modularity of PRC1 composition and chromatin interaction define condensate properties. Molecular cell 29 38521066
2020 SUMOylated PRC1 controls histone H3.3 deposition and genome integrity of embryonic heterochromatin. The EMBO journal 29 32395866
2022 PRC1-mediated epigenetic programming is required to generate the ovarian reserve. Nature communications 28 35948547
2021 Independent domains for recruitment of PRC1 and PRC2 by human XIST. PLoS genetics 27 33750950
2020 Functional loss of a noncanonical BCOR-PRC1.1 complex accelerates SHH-driven medulloblastoma formation. Genes & development 27 32820036
2017 Protein Regulator of Cytokinesis PRC1 Confers Chemoresistance and Predicts an Unfavorable Postoperative Survival of Hepatocellular Carcinoma Patients. Journal of Cancer 26 28382142
2023 Aberrant gene activation in synovial sarcoma relies on SSX specificity and increased PRC1.1 stability. Nature structural & molecular biology 25 37735617
2021 Reprogramming CBX8-PRC1 function with a positive allosteric modulator. Cell chemical biology 24 34715055
2019 Kinesin-6 Klp9 plays motor-dependent and -independent roles in collaboration with Kinesin-5 Cut7 and the microtubule crosslinker Ase1 in fission yeast. Scientific reports 24 31089172
2013 MAP65 coordinate microtubule growth during bundle formation. PloS one 24 23437247
2023 Uncoupled evolution of the Polycomb system and deep origin of non-canonical PRC1. Communications biology 22 37949928
2021 Therapeutic targeting of the PLK1-PRC1-axis triggers cell death in genomically silent childhood cancer. Nature communications 22 34531368
2019 Microtubule bundling by MAP65-1 protects against severing by inhibiting the binding of katanin. Molecular biology of the cell 22 31017848
2019 MYCN and PRC1 cooperatively repress docosahexaenoic acid synthesis in neuroblastoma via ELOVL2. Journal of experimental & clinical cancer research : CR 22 31856871
2024 PRC1 directs PRC2-H3K27me3 deposition to shield adult spermatogonial stem cells from differentiation. Nucleic acids research 21 38142439
2023 Targeted Degradation of PRC1 Components, BMI1 and RING1B, via a Novel Protein Complex Degrader Strategy. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 21 36737841
2013 Microtubule organization by kinesin motors and microtubule crosslinking protein MAP65. Journal of physics. Condensed matter : an Institute of Physics journal 21 23945219
2020 The genetic basis for PRC1 complex diversity emerged early in animal evolution. Proceedings of the National Academy of Sciences of the United States of America 20 32868440
2022 PRC1 and RACGAP1 are Diagnostic Biomarkers of Early HCC and PRC1 Drives Self-Renewal of Liver Cancer Stem Cells. Frontiers in cell and developmental biology 19 35445033
2018 Chromatin modulation and gene regulation in plants: insight about PRC1 function. Biochemical Society transactions 19 30065110
2016 The evolutionary landscape of PRC1 core components in green lineage. Planta 19 26729480
2022 PRC1 sustains the integrity of neural fate in the absence of PRC2 function. eLife 17 34994686
2020 Ase1 domains dynamically slow anaphase spindle elongation and recruit Bim1 to the midzone. Molecular biology of the cell 17 32997572
2020 Structure and Role of BCOR PUFD in Noncanonical PRC1 Assembly and Disease. Biochemistry 16 32628469
2022 A noncoding regulatory RNA Gm31932 induces cell cycle arrest and differentiation in melanoma via the miR-344d-3-5p/Prc1 (and Nuf2) axis. Cell death & disease 15 35393397
2010 Tobacco microtubule-associated protein, MAP65-1c, bundles and stabilizes microtubules. Plant molecular biology 15 20878450
2025 Dynamic PRC1-CBX8 stabilizes a porous structure of chromatin condensates. Nature structural & molecular biology 14 39815045
2021 Gradual compaction of the central spindle decreases its dynamicity in PRC1 and EB1 gene-edited cells. Life science alliance 14 34580180
2020 PRC1 is a critical regulator for anaphase spindle midzone assembly and cytokinesis in mouse oocyte meiosis. The FEBS journal 14 33206458
2017 The microtubule-associated protein PRC1 is a potential therapeutic target for lung cancer. Oncotarget 14 29435157
2014 Replicative stress induces intragenic transcription of the ASE1 gene that negatively regulates Ase1 activity. Current biology : CB 14 24768052
2022 PCGF1-PRC1 links chromatin repression with DNA replication during hematopoietic cell lineage commitment. Nature communications 13 36443290
2020 PRC1 catalytic unit RING1B regulates early neural differentiation of human pluripotent stem cells. Experimental cell research 13 32971117
2018 p27Kip1 regulates the microtubule bundling activity of PRC1. Biochimica et biophysica acta. Molecular cell research 13 30327204
2010 MAP65 in tubulin/colchicine paracrystals of Vigna sinensis root cells: possible role in the assembly and stabilization of atypical tubulin polymers. Cytoskeleton (Hoboken, N.J.) 13 20217678
2000 Expression of PTTG and prc1 genes during telencephalic neurogenesis. Mechanisms of development 13 10727870
2023 Phosphorylation controls spatial and temporal activities of motor-PRC1 complexes to complete mitosis. The EMBO journal 11 37592895
2023 Functional dissection of PRC1 subunits RYBP and YAF2 during neural differentiation of embryonic stem cells. Nature communications 11 37935677
2020 CENPE, PRC1, TTK, and PLK4 May Play Crucial Roles in the Osteosarcoma Progression. Technology in cancer research & treatment 11 33176597
2022 PRC1-independent binding and activity of RYBP on the KSHV genome during de novo infection. PLoS pathogens 10 36026503
2022 AUTS2 Controls Neuronal Lineage Choice Through a Novel PRC1-Independent Complex and BMP Inhibition. Stem cell reviews and reports 10 36258139
2024 Discovery and Characterization of a Novel Cereblon-Recruiting PRC1 Bridged PROTAC Degrader. Journal of medicinal chemistry 9 38607318
2023 Dispersal of PRC1 condensates disrupts polycomb chromatin domains and loops. Life science alliance 9 37487640
2022 PRC1 chromatin factors strengthen the consistency of neuronal cell fate specification and maintenance in C. elegans. PLoS genetics 9 35604893
2022 Structure and Function of the Polycomb Repressive Complexes PRC1 and PRC2. International journal of molecular sciences 9 35682651

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