| 1998 |
PRC1 (protein regulator of cytokinesis 1) is a substrate for CDKs in vitro and is phosphorylated in vivo at CDK consensus sites; it localizes to the nucleus in interphase, associates dynamically with mitotic spindles during mitosis, and localizes to the midbody during cytokinesis. Microinjection of anti-PRC1 antibodies blocked cellular cleavage but not nuclear division, establishing a direct role in cytokinesis. |
In vitro kinase assay, in vivo phosphorylation, microinjection of inhibitory antibodies, immunolocalization |
Molecular cell |
High |
9885575
|
| 2002 |
PRC1 binds and bundles microtubules both in vivo and in vitro; CDK phosphorylation suppresses its bundling activity during mitosis (a phosphorylation-null mutant causes aberrant prometaphase bundling); siRNA depletion abolishes microtubule interdigitation and the spindle midzone. The NH2-terminal region is required for localization to the cleavage furrow and midbody center, whereas the central region is required for microtubule binding and bundling. |
siRNA knockdown, overexpression of truncation/phosphorylation-null mutants, in vitro microtubule bundling assay, immunofluorescence |
The Journal of cell biology |
High |
12082078
|
| 2013 |
PRC1 and kinesin-4 (Kif4A) cooperate to tag microtubule plus ends in a length-dependent manner in vitro and in dividing cells. The crystal structure of the PRC1 homodimer was determined and protein-protein interactions required for microtubule plus-end tagging were mapped. |
In vitro reconstitution, crystal structure determination, live-cell imaging, structure-guided mutagenesis |
Cell |
High |
23870126
|
| 2018 |
CDK16 (in complex with Cyclin Y) phosphorylates PRC1 at Thr481; specific inhibition of CDK16 causes PRC1 dephosphorylation at this site and its delocalization to the nucleus during interphase. CDK16 inhibition and PRC1 downregulation show epistatic effects on cell viability, placing them in the same pathway. |
Analog-sensitive CDK16 generated by CRISPR-Cas9, proteomic substrate identification, phosphosite mapping, epistasis analysis |
Experimental & molecular medicine |
High |
30992425
|
| 2022 |
CDK16 phosphorylates PRC1 to regulate spindle formation during mitosis in triple-negative breast cancer cells; CDK16 knockdown or pharmacological inhibition leads to mitotic spindle defects consistent with PRC1 dysfunction. |
Genetic knockdown, pharmacological inhibition, xenograft and organoid models, transcriptomic analysis |
Journal of experimental & clinical cancer research |
Medium |
35449080
|
| 2020 |
PRC1 acts as a mechanical dashpot (velocity-dependent friction generator) when crosslinking antiparallel microtubules: frictional forces scale with microtubule sliding velocity and number of PRC1 crosslinks, but not overlap length or PRC1 density within overlaps. |
Simultaneous optical trapping and TIRF microscopy in vitro |
Developmental cell |
High |
32640202
|
| 2016 |
In metaphase spindles, PRC1-GFP-labeled overlap (bridging) bundles show one-to-one association with kinetochore pairs (>90% of overlap bundles bridge sister k-fibers); PRC1 knockdown reduces bridging fiber thickness and interkinetochore distance, demonstrating PRC1's role in spindle force balance. |
Live-cell imaging with PRC1-GFP, siRNA knockdown, endogenous PRC1 immunolocalization, quantitative analysis |
EMBO reports |
High |
28028032
|
| 2018 |
The geometry of antiparallel microtubule arrays regulates PRC1-Kif4A activity: sliding velocity scales with initial microtubule overlap length, and final overlap width scales with microtubule length. PRC1 and Kif4A accumulate at microtubule plus-ends forming 'end-tags,' and sliding stalls when opposing end-tags collide. |
In vitro reconstitution with fluorescently labeled proteins, TIRF microscopy |
eLife |
High |
30353849
|
| 2021 |
PLK1 activates PRC1 to promote cytokinesis; the EWSR1-FLI1 oncogenic transcription factor hijacks PRC1 via binding to a proximal GGAA-microsatellite enhancer, driving high PRC1 expression. PLK1 inhibition in PRC1-overexpressing Ewing sarcoma triggers mitotic catastrophe and tumor regression. |
CRISPR-mediated enhancer editing, in vitro and in vivo functional experiments, transcriptome profiling |
Nature communications |
Medium |
34531368
|
| 2020 |
PRC1 is required for anaphase spindle midzone and midbody formation during mouse oocyte meiosis I; KIF4A co-localizes with PRC1 at the midzone, and KIF4A depletion disrupts PRC1 expression and localization, placing KIF4A upstream of PRC1 in midzone assembly during meiosis. |
siRNA knockdown, immunofluorescence localization, mRNA rescue injection, mouse oocyte model |
The FEBS journal |
Medium |
33206458
|
| 2017 |
ZFP36 binds to AU-rich elements in the 3'UTR of PRC1 mRNA to downregulate PRC1 protein expression; this post-transcriptional regulation by ZFP36 suppresses PRC1-mediated promotion of cell proliferation in hepatocellular carcinoma. |
Luciferase reporter assay, ribonucleoprotein immunoprecipitation, overexpression and knockdown |
Frontiers in molecular biosciences |
Medium |
32766276
|
| 2014 |
PRC1 crystal structure of the homodimer was determined (as part of the Subramanian et al. 2013 study), mapping the spectrin-like fold and identifying interaction surfaces required for antiparallel microtubule crosslinking and kinesin-4 co-recruitment. |
X-ray crystallography, in vitro reconstitution, structure-guided mutagenesis |
Cell |
High |
23870126
|
| 1997 |
The budding yeast ortholog Ase1 (PRC1 family) undergoes APC/cyclosome-mediated proteolysis when cells exit mitosis and enter G1; stable non-degradable Ase1 delays spindle disassembly and causes a spindle defect sensed by the spindle assembly checkpoint, establishing APC-mediated proteolysis as a regulator of spindle assembly and disassembly. |
Genetic analysis, cell-cycle-specific degradation assays, expression of non-degradable mutant |
Science |
High |
9036857
|
| 2005 |
Fission yeast Ase1 (PRC1 ortholog) localizes to microtubule overlapping zones and is a dose-dependent microtubule-bundling factor; its absence causes spindle collapse during anaphase B, and Aurora kinase fails to localize to central spindles without Ase1. Ase1 also acts as a regulatory component in the cytokinesis checkpoint. |
Gene deletion, time-lapse imaging, overexpression analysis, genetic epistasis |
Molecular biology of the cell |
High |
15647375
|
| 2020 |
In budding yeast, the Ase1 spectrin domain promotes midzone recruitment before anaphase onset and slows early spindle elongation via conserved basic residues; the carboxy-terminal domain interacts with and recruits EB1/Bim1 to the midzone to maintain midzone length during late anaphase. |
Domain truncation and mutagenesis, live-cell imaging, protein interaction assays |
Molecular biology of the cell |
Medium |
32997572
|
| 2019 |
In fission yeast, Ase1 (PRC1 ortholog) is required for bipolar spindle assembly in the absence of kinesin-5 by recruiting CLASP/Cls1 to stabilize microtubules; Brownian dynamics simulations confirm that Ase1 and Cls1 activity are sufficient for initial bipolar spindle formation via microtubule polymerization forces. |
Genetic epistasis, live-cell imaging, computational modeling |
Nature communications |
Medium |
28513584
|
| 2014 |
Replication stress in budding yeast induces intragenic transcription of ASE1, producing shorter protein isoforms that localize to the spindle and antagonize full-length Ase1 at the midzone, stabilizing the S-phase spindle by downregulating full-length Ase1 crosslinking activity. |
Biochemical characterization of short isoforms, overexpression, live-cell imaging, genetic analysis |
Current biology |
Medium |
24768052
|
| 2024 |
Canonical PRC1 (the Polycomb epigenetic complex) forms condensates synergistically with nucleosomal arrays (reducing critical concentration >20-fold); CBX subunit composition determines condensate initiation, and PHC2's polymerization activity promotes distinct adherent domain formation that does not coalesce. Live-cell imaging confirms CBX drives initiation and PHC drives stability. |
In vitro reconstitution with single-molecule imaging, live-cell imaging, genetic perturbation of specific subunits |
Molecular cell |
High |
38521066
|
| 2014 |
Crystal structure of the human Ring1B-Bmi1-UbcH5c PRC1 ubiquitylation module bound to the nucleosome core particle reveals that PRC1 achieves substrate specificity by contacting multiple nucleosome surfaces distinct from the catalytic site, and reveals an unexpected role for the E2 enzyme UbcH5c in substrate recognition for H2A Lys119 ubiquitylation. |
X-ray crystallography of PRC1-nucleosome complex |
Nature |
High |
25355358
|
| 2016 |
RYBP/YAF2 stimulates the H2AK119 E3 ubiquitin ligase activity of PRC1; RYBP shapes H2AK119 mono-ubiquitylation at PcG targets and underpins activity-based communication between PRC1 and PRC2 required for normal H3K27me3. Loss of RYBP erodes repressive Polycomb chromatin domains. |
Mouse ESC genetic perturbation, quantitative genomics, ChIP-seq |
eLife |
High |
27705745
|
| 2012 |
Recombinant PRC1 (Polycomb complex) inhibits transcription on H3K27-methylated chromatin templates by blocking recruitment of Mediator and dissociating preassembled preinitiation complexes, while leaving TBP/TFIID relatively intact, defining a specific biochemical mechanism for PRC1-mediated transcriptional silencing. |
In vitro transcription reconstitution on immobilized chromatin templates, purified recombinant PRC1 |
The Journal of biological chemistry |
High |
22910904
|
| 2021 |
Rapid degron-based depletion of PRC1 (Polycomb complex) shows it functions independently of PRC2 to counteract RNA Pol II binding and transcription initiation; single-cell analysis reveals PRC1 controls transcriptional burst frequency uniformly across the cell population. |
Auxin-inducible degron (rapid depletion), time-resolved ChIP-seq and RNA-seq, single-cell gene expression analysis |
Nature structural & molecular biology |
High |
34608337
|
| 2020 |
RYBP and YAF2 each specifically bind H2AK119ub1 to recruit RYBP-PRC1 or YAF2-PRC1 and catalyze ubiquitination of neighboring nucleosomes via a positive-feedback model; histone H1-compacted chromatin enhances distal propagation of H2AK119ub1, contributing to epigenetic inheritance during cell division. |
Biochemical binding assays, reconstitution, genetic disruption, chromatin fractionation |
Nature cell biology |
High |
32203418
|
| 2017 |
hnRNPK is the principal RNA-binding protein that binds the Xist B-repeat-containing Polycomb Interaction Domain (XR-PID) and recruits PCGF3/5-PRC1 to initiate chromosome-wide H2AK119ub1 and subsequent PRC2 recruitment; synthetic tethering of hnRNPK to Xist lacking XR-PID is sufficient to restore Polycomb recruitment. |
RNA deletion mapping, RNA pulldown, synthetic tethering, genetic deletion, ChIP-seq |
Molecular cell |
High |
29220657
|
| 2017 |
PCGF3/5-PRC1 initiates Polycomb recruitment in X chromosome inactivation; it catalyzes H2AK119ub1 chromosome-wide, which signals recruitment of other PRC1 complexes and PRC2, the latter leading to H3K27me3 deposition. Pcgf3/5 knockout results in female-specific embryo lethality and abrogates Xist-mediated gene repression. |
Conditional knockout, ChIP-seq, immunofluorescence, RNA-seq |
Science |
High |
28596365
|
| 2016 |
The Sfmbt subunit of PhoRC and the Scm subunit of canonical PRC1 directly bind each other through their SAM domains; the 1.9 Å crystal structure reveals the recognition mechanism and shows Sfmbt-SAM lacks polymerization capacity. PRE-tethered Sfmbt-SAM nucleates PRC1 recruitment via Scm-SAM, and Scm-SAM/Ph-SAM polymerization drives PRC1-compacted chromatin formation. |
X-ray crystallography (1.9 Å), in vitro binding assays, Drosophila functional genetics |
Genes & development |
High |
27151979
|
| 2016 |
BMI1's central domain adopts a ubiquitin-like (UBL) fold that binds PHC2 in a β-hairpin conformation and also mediates BMI1 homo-oligomerization; both BMI1-PHC2 interaction and UBL-domain homo-oligomerization are required for H2A ubiquitination activity of PRC1 and clonogenic potential of cancer cells. |
NMR spectroscopy, X-ray crystallography, H2A ubiquitination assay, clonogenic assay |
Nature communications |
High |
27827373
|
| 2020 |
SUMOylated CBX2-containing PRC1 recruits the H3.3-specific chaperone DAXX to paternal pericentric heterochromatin (pat-PCH) in mouse pre-implantation embryos, enabling H3.3 incorporation; loss of Daxx, Ring1, or Rnf2 abrogates H3.3 incorporation and causes chromatin breakage and mis-segregation of paternal chromosomes. |
Genetic knockdown/knockout in mouse embryos, immunofluorescence, complementation assays |
The EMBO journal |
High |
32395866
|
| 2015 |
Cbx2 directs catalytically active PRC1 to paternal pericentric heterochromatin (pat-PCH) in mouse zygotes via its chromodomain binding H3K27me3 and an AT-hook binding AT-rich major satellites; HP1β at maternal PCH prevents Cbx2 AT-hook from accessing DNA there, establishing a parent-of-origin-specific PRC1 targeting mechanism. |
Mouse zygote genetics, domain mutation analysis, immunofluorescence, loss-of-function studies |
Molecular cell |
High |
25801166
|
| 2021 |
Single-particle tracking in live mouse ESCs shows PRC1 (Polycomb complex) is highly dynamic with only a small fraction stably bound to chromatin, and exhibits low occupancy at target sites; specific subunits define kinetics (CBX for chromatin binding, other subunits for complex stability), suggesting chromatin modification rather than complex occupancy is central to gene repression. |
Single-particle tracking in live cells (SPT), genome engineering, chromatin fraction analysis |
Nature communications |
High |
33563969
|
| 2023 |
PRC2.1 catalyzes most H3K27me3 at Polycomb targets and promotes recruitment of CBX2/4-cPRC1 but not CBX7-cPRC1; conversely, the PRC2.2 accessory protein JARID2 is specifically required for CBX7-cPRC1 recruitment and consequent 3D chromatin interactions, defining distinct mechanisms by which PRC2.1 and PRC2.2 recruit different canonical PRC1 forms. |
CRISPR knockout and genetic replacement of subunit-specific factors, ChIP-seq, Hi-C, Co-IP |
Molecular cell |
High |
37030288
|
| 2020 |
Canonical PRC1, but not variant PRC1, can maintain gene silencing through cell division upon removal of tethering signal, via cis-acting H2AK119ub1 and H3K27me3 promoting a sequence-independent feedback recruitment of PcG proteins. |
Reversible tethering of PcG proteins to ectopic sites in mouse ESCs, ChIP-seq, RNA-seq |
Nature communications |
High |
31036804
|
| 2019 |
Variant PRC1 complexes (not canonical PRC1) are the primary drivers of Polycomb-mediated gene repression; distinct pools of H2A monoubiquitylation from different variant PRC1 complexes are associated with target gene repression and X chromosome inactivation silencing. Canonical PRC1 contributes to higher-order chromatin structures but little to gene repression. |
Combinatorial genetic perturbation, quantitative genomics (ChIP-seq, RNA-seq) in mouse ESCs |
Molecular cell |
High |
31029541
|
| 2020 |
Canonical PRC1 mediates long-range chromatin interactions (bridging megabase-scale loci) independently of CTCF; impairment of PRC1 enzymatic activity does not directly disrupt these interactions, and transcriptional activation is separable from loss of PRC1-mediated interactions. |
Hi-C, imaging, genetic loss of function in mouse ESCs |
Genes & development |
High |
32439634
|