Affinage

ZWILCH

Protein zwilch homolog · UniProt Q9H900

Length
591 aa
Mass
67.2 kDa
Annotated
2026-06-11
65 papers in source corpus 26 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ZWILCH is an obligate subunit of the metazoan ROD-Zwilch-ZW10 (RZZ) complex, a kinetochore-localized scaffold that drives spindle assembly checkpoint (SAC) signaling and fibrous corona formation during mitosis (PMID:12686595, PMID:15824131). Identified as the third RZZ component by immunoaffinity purification, it co-immunoprecipitates with ZW10 and ROD and localizes to prometaphase kinetochores, where its loss produces lagging chromosomes and precocious sister separation identical to zw10 and rod mutants (PMID:12686595). Crystallography revealed ZWILCH as a distinct structural subunit within RZZ, and cryo-EM established that RZZ resembles self-assembling cytosolic coat scaffolds and serves as dynein's cargo at kinetochores via direct, farnesylation-dependent binding of the dynein adaptor Spindly (PMID:20462495, PMID:28320825). RZZ-Spindly units oligomerize into a filamentous meshwork to build the fibrous corona, a process driven by ROD oligomerization and triggered by MPS1 kinase phosphorylation; mutation of ZWILCH residues implicated in Spindly binding abolishes corona expansion (PMID:29915359, PMID:30415699, PMID:30415700, PMID:35373361). The complex's primary checkpoint role is to tether Mad1-Mad2 to unattached kinetochores, providing a recruitment pathway separable from the KNL1-Bub3-Bub1 axis, while dynein-dynactin loading (coordinated with CENP-E) strips RZZ and Mad2 from attached kinetochores to silence the SAC (PMID:30415699, PMID:30415700, PMID:17576797, PMID:26651294, PMID:37984321). RZZ kinetochore recruitment depends on Bub1, and corona assembly is integrated through nonredundant BUB1-ROD and CENP-E-BUBR1 branches; removal is timed by Polo kinase phosphorylation of Spindly, which uncouples Spindly from ZWILCH (PMID:26031201, PMID:31849090, PMID:40938979). Somatic ZWILCH mutations occur in chromosomally unstable colorectal cancers (PMID:15126332).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2003 High

    Established ZWILCH as a bona fide third subunit of the RZZ complex with a dedicated role in chromosome segregation, distinguishing it from a generic kinetochore protein.

    Evidence Immunoaffinity purification, mass spectrometry, and genetic mutant analysis in Drosophila plus co-IP in human cells

    PMID:12686595

    Open questions at the time
    • Did not resolve ZWILCH's specific molecular contribution within the complex
    • No structural information on the subunit
  2. 2005 High

    Defined the functional output of RZZ by showing it is essential for stable Mad1-Mad2 recruitment to unattached kinetochores, separating it from a distinct Zwint-1/Mis12/Ndc80 complex.

    Evidence Reciprocal co-IP and RNAi depletion in human cells and Xenopus egg extracts

    PMID:15824131

    Open questions at the time
    • Mechanism of Mad1-Mad2 tethering by RZZ unresolved
    • ZWILCH-specific role in Mad1 recruitment not isolated
  3. 2007 High

    Placed RZZ atop the dynein recruitment hierarchy, defining its role as the kinetochore platform for Spindly and dynein and for SAC silencing by Mad2/RZZ stripping.

    Evidence RNAi epistasis by double depletion in Drosophila S2 and human cells with live imaging

    PMID:17576797

    Open questions at the time
    • Direct binding interface between RZZ and Spindly not mapped
    • ZWILCH versus ROD contribution to Spindly docking unknown
  4. 2008 High

    Clarified the dynamics and Zwint-1 dependence of stable RZZ kinetochore residency required for checkpoint arrest, and showed RZZ restrains load-bearing attachment formation via dynein/SPDL-1.

    Evidence FRAP with hZW10 mutagenesis and co-IP in human cells; RNAi epistasis in C. elegans embryos

    PMID:18268100 PMID:18765790

    Open questions at the time
    • Later work revised Zwint-1 as the recruitment determinant
    • ZWILCH-specific stability contribution not separated from ZW10
  5. 2010 High

    Provided the first atomic view of ZWILCH and defined RZZ architecture, revealing a coat-protein-like ROD scaffold and mutually exclusive ZW10 incorporation that distinguishes RZZ from the related NRZ complex.

    Evidence X-ray crystallography of ZWILCH and in vitro binding assays with structural modeling

    PMID:20462495

    Open questions at the time
    • Structure of the assembled holocomplex not yet determined
    • Functional role of the ZWILCH fold not assigned
  6. 2011 Medium

    Identified upstream kinase control of RZZ kinetochore loading, showing MPS1 maintains RZZ/Mad1 residency and Aurora B promotes loading via Zwint-1 phosphorylation.

    Evidence Reversine MPS1 inhibition with immunofluorescence; in vitro Aurora B kinase assay, MS phosphosite mapping, and non-phosphorylatable mutants

    PMID:20624901 PMID:21775627

    Open questions at the time
    • No direct biochemical reconstitution of kinase-regulated RZZ loading
    • ZWILCH not a direct kinase substrate in these studies
  7. 2014 Medium

    Showed RZZ/Mad1 kinetochore retention is governed by a CENP-I/Aurora B molecular switch that sustains checkpoint signaling until mature attachments form.

    Evidence siRNA co-depletion epistasis and live imaging in human cells

    PMID:24862574

    Open questions at the time
    • No reconstitution of the proposed switch
    • Direct CENP-I-RZZ binding not established
  8. 2015 High

    Revised the RZZ recruitment model to Bub1-dependence and established RZZ as a Mad1-Mad2 recruitment pathway parallel to and separable from KNL1-Bub3-Bub1.

    Evidence Bub1 domain-mapping mutagenesis with RNAi; siRNA depletion and live imaging in diploid RPE-1 cells

    PMID:26031201 PMID:26651294

    Open questions at the time
    • Direct Bub1-RZZ binding interface not resolved at this stage
    • How two Mad1 pathways are coordinated unclear
  9. 2017 High

    Established the molecular basis of RZZ as dynein cargo, showing it resembles coat scaffolds and binds farnesylated Spindly directly, with ROD as the farnesyl receptor.

    Evidence Single-particle cryo-EM, cross-linking MS, biochemical reconstitution, and targeted chemical biology

    PMID:28320825

    Open questions at the time
    • ZWILCH contribution to Spindly binding not fully isolated from ROD
    • Mechanism converting binding into corona assembly not yet defined
  10. 2018 High

    Defined the corona-building mechanism, demonstrating RZZ-Spindly self-assembly into filaments driven by ROD oligomerization and MPS1 phosphorylation, with ZWILCH Spindly-binding residues required.

    Evidence In vitro filament reconstitution, mutagenesis of ZWILCH residues, RNAi/genome editing, and kinetochore expansion assays in human cells and C. elegans

    PMID:29915359 PMID:30415699 PMID:30415700

    Open questions at the time
    • Atomic details of filament nucleation not resolved at this stage
    • Precise ZWILCH-Spindly contact geometry unmapped
  11. 2019 High

    Resolved the primary function of RZZ as Mad1 localization (forced Mad1 tethering bypasses Rod) and defined Polo-kinase timing of RZZ removal via Spindly-ZWILCH uncoupling, plus ULK1- and Chmp4c-dependent regulation of RZZ/Mad1.

    Evidence CRISPR/RNAi with PLA and Mad1-tethering rescue; in vitro Polo kinase assay with Spindly-ZWILCH co-IP and Drosophila RNAi screen; ULK1 and Chmp4c in vitro kinase/co-IP and depletion studies

    PMID:29362225 PMID:30782962 PMID:31291454 PMID:31849090

    Open questions at the time
    • Structural basis of Polo-regulated Spindly-ZWILCH dissociation not solved
    • ULK1 and Chmp4c links to ZWILCH are indirect
  12. 2022 High

    Provided high-resolution structural and mechanistic detail of corona assembly, defining the ROD farnesyl-binding site and showing MPS1 is necessary and sufficient for phosphorylation-dependent RZZS filament nucleation.

    Evidence High-resolution cryo-EM, in vitro corona assembly and kinase assays, and mutagenesis

    PMID:35373361

    Open questions at the time
    • In vivo regulation of nucleation thresholds not fully defined
    • ZWILCH-specific structural role within polymer not isolated
  13. 2023 High

    Integrated CENP-E into the corona pathway as the receptor for dynein-dynactin loading and a second RZZS receptor, and biophysically defined ZWILCH (ZWL-1) as the primary Spindly-C interactor in C. elegans.

    Evidence siRNA/MPS1 inhibition, phosphomimetic rescue, and co-IP in human cells; NMR and biophysical binding assays of Spindly-C with ROD-1 and ZWL-1

    PMID:33450249 PMID:37984321

    Open questions at the time
    • Relative ROD versus ZWILCH Spindly binding may differ between species
    • Structure of CENP-E-RZZS complex not solved
  14. 2025 High

    Defined nonredundant corona assembly branches in which BUB1 binds ROD directly and CENP-E links BUBR1 to RZZ, unifying the kinase-, adaptor-, and motor-dependent assembly logic.

    Evidence Biochemical reconstitution, co-IP, and kinetochore expansion assays with genetic depletion

    PMID:40938979

    Open questions at the time
    • ZWILCH-specific role in the BUB1-ROD branch not isolated
    • Quantitative contribution of each branch in vivo unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ZWILCH's distinct structural fold mechanistically contributes to filament polymerization, Spindly binding, and Mad1 recruitment within the assembled corona—beyond mapped binding residues—remains unresolved.
  • No structure of the fully assembled RZZS corona polymer at atomic resolution
  • ZWILCH-specific function not cleanly separated from ROD/ZW10 in most assays
  • Physiological consequence of cancer-associated ZWILCH mutations untested functionally

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 5 GO:0060090 molecular adaptor activity 3
Localization
GO:0005694 chromosome 3 GO:0005815 microtubule organizing center 3
Pathway
R-HSA-1640170 Cell Cycle 4
Partners
BUB1CENP-EMAD1RODSPINDLYZW10ZWINT-1
Complex memberships
RZZ (ROD-Zwilch-ZW10) complexfibrous corona

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Zwilch was identified as a third component of the ZW10/ROD complex (RZZ complex) by immunoaffinity chromatography and mass spectrometry of Drosophila proteins. Zwilch localizes to kinetochores and kinetochore microtubules identically to ZW10 and ROD. zwilch mutants exhibit lagging chromosomes at anaphase and precocious sister chromatid separation upon spindle checkpoint activation—phenotypes identical to zw10 and rod mutations. Human Zwilch (hZwilch) co-immunoprecipitates with hZW10 and hROD from HeLa cell extracts and localizes to kinetochores at prometaphase. Immunoaffinity chromatography, mass spectrometry, genetic mutant analysis, co-immunoprecipitation, immunofluorescence Molecular biology of the cell High 12686595
2005 In mitotic human cells, ZW10 resides in a complex with Rod and Zwilch (the RZZ complex), distinct from a separate complex containing Zwint-1, Mis12, and Ndc80-Hec1. The ZW10/RZZ complex is essential for stable binding of the Mad1–Mad2 complex to unattached kinetochores, demonstrated by depletion in human cells and Xenopus egg extracts. Zwint-1 is critical for recruiting ZW10 to unattached kinetochores. Co-immunoprecipitation, RNAi depletion in human cells and Xenopus egg extracts, immunofluorescence The Journal of cell biology High 15824131
2010 X-ray crystal structure of ZWILCH was solved, revealing a novel fold distinct from RINT1 (the analogous subunit in the NRZ complex). Structural and biochemical analysis of the RZZ complex showed that ROD contains an N-terminal beta-propeller followed by an alpha-solenoid (architecture shared with nucleoporins and vesicle coat subunits), and that ZW10 binding to ROD and NAG (a ROD homolog) is mutually exclusive, placing Zwilch and RINT1 as distinct additional subunits of the RZZ and NRZ complexes respectively. X-ray crystallography, in vitro binding assays, bioinformatics/structural modeling Structure (London, England : 1993) High 20462495
2017 Cryo-EM structure of the human RZZ complex was determined, showing it is structurally related to self-assembling cytosolic coat scaffolds (Clathrin, Sec13-Sec31, αβ'ε-COP). Spindly (a dynein adaptor) binds RZZ directly in a farnesylation-dependent but membrane-independent manner, with ROD identified as the Spindly farnesyl receptor through targeted chemical biology. This establishes RZZ as dynein's cargo at human kinetochores. Single-particle cryo-EM, cross-linking mass spectrometry, biochemical reconstitution, targeted chemical biology (farnesyl receptor mapping) The Journal of cell biology High 28320825
2018 The dynein adaptor Spindly and the RZZ complex drive kinetochore expansion (fibrous corona formation) in a dynein-independent manner. C-terminal farnesylation of Spindly and MPS1 kinase activity cause Spindly conformational changes that promote oligomerization of RZZ-Spindly complexes into a filamentous meshwork both in cells and in vitro. ZWILCH residues implicated in Spindly binding are required for corona expansion. siRNA knockdown, in vitro reconstitution of filamentous meshwork, cell biology (kinetochore expansion assays), mutagenesis of ZWILCH Spindly-binding residues Nature cell biology High 29915359
2018 RZZ complex self-assembles into filaments in a concentration-dependent manner driven by ROD oligomerization, and this underlies kinetochore expansion (fibrous corona formation). ROD depletion suppresses kinetochore expansion, as does mutation of ZWILCH residues implicated in Spindly binding. In C. elegans, a minimal ROD-1/Zw10 complex efficiently oligomerizes into filaments in vitro. RZZ's sole role in SAC activation is to tether Mad1-Mad2 to kinetochores; separately, Mps1 kinase triggers fibrous corona formation by phosphorylating two N-terminal sites on Rod. In vitro reconstitution of RZZ filaments, mutagenesis, RNAi knockdown, genome editing in human cells, cell biology Current biology : CB High 30415699 30415700
2022 High-resolution cryo-EM structure of the RZZ complex was determined, including a farnesyl-binding site on ROD required for Spindly binding. Using an in vitro assay, MPS1 kinase was shown to be necessary and sufficient for corona assembly at supercritical RZZ-Spindly concentrations, and the molecular mechanism of phosphorylation-dependent filament nucleation was described. Structural determinants of RZZS polymerization and kinetochore localization of Spindly were identified. High-resolution cryo-EM, in vitro corona assembly assay, kinase activity assays, mutagenesis The EMBO journal High 35373361
2008 Stable hZW10 kinetochore residency during prometaphase (at unattached kinetochores) depends on its interaction with hZwint-1. FRAP analysis showed hZW10 has a short half-time (~13 s) at metaphase kinetochores but is stabilized at unattached kinetochores in a Zwint-1-dependent manner. This stable residency is essential for mitotic checkpoint arrest. The RZZ complex (including Zwilch) requires Zwint-1 for stable kinetochore association. FRAP (fluorescence recovery after photobleaching), mutagenesis screen of hZW10, co-immunoprecipitation, RNAi The Journal of cell biology High 18268100
2007 Cytoplasmic dynein requires the RZZ complex (Rod-Zw10-Zwilch) at kinetochores for its kinetochore localization; depletion of Spindly abolishes dynein kinetochore targeting but leaves RZZ levels intact. Conversely, depletion of the RZZ complex abolishes both Spindly and dynein targeting to kinetochores. Dynein, via the RZZ complex, is responsible for stripping Mad2 and RZZ from aligned kinetochores to silence the SAC. RNAi screen in Drosophila S2 cells, siRNA in human cells, immunofluorescence, live imaging The Journal of cell biology High 17576797
2009 Human Spindly kinetochore localization is controlled by the RZZ complex and Aurora B kinase. Depletion of hSpindly results in reduced inter-kinetochore tension, unstable kinetochore fibers, prometaphase delay, and severe chromosome misalignment. Co-depletion of dynein rescues the spindle rotation phenotype caused by hSpindly depletion, placing dynein downstream of hSpindly in spindle orientation. siRNA knockdown, live-cell imaging, immunofluorescence, epistasis by co-depletion The Journal of cell biology High 19468067
2008 In C. elegans, the RZZ complex is required for Mad2 targeting to kinetochores and spindle checkpoint activation. The associated protein SPDL-1 mediates dynein/dynactin targeting to kinetochores via RZZ. RZZ complex inhibition alone slows but does not prevent load-bearing kinetochore-microtubule attachment formation; SPDL-1 inhibition (which removes dynein without perturbing RZZ) prevents stable end-on attachments. Co-inhibition of SPDL-1 and RZZ reduces phenotypic severity to that of RZZ inhibition alone, demonstrating RZZ inhibits load-bearing attachment formation, normally controlled by dynein via SPDL-1. RNAi in C. elegans embryo, genetic epistasis (double inhibition), live imaging, chromosome segregation assays Genes & development High 18765790
2010 MPS1 kinase inhibition by reversine causes ejection of Mad1 and the ROD-ZWILCH-ZW10 (RZZ) complex from unattached kinetochores, demonstrating that MPS1 activity is required for maintaining RZZ and Mad1 at kinetochores. MPS1 acts downstream of Aurora B in the error correction pathway. Small molecule inhibitor (reversine), immunofluorescence in HeLa cells, epistasis with Aurora B The Journal of cell biology Medium 20624901
2011 Aurora B kinase phosphorylates Zwint-1 (not ZW10) at three novel sites in vitro (identified by tandem MS). Expression of non-phosphorylatable triple-Ala zwint-1 mutant blocked kinetochore assembly of RZZ-dependent proteins (including Zwilch) and induced defects in chromosome movement. Aurora B inhibition reduced accumulation of dynein and the RZZ complex at kinetochores, but this reflected loss of Zwint-1 phosphorylation rather than direct dynein phosphorylation. In vitro kinase assay, tandem mass spectrometry, mutagenesis (triple-Ala and triple-Glu mutants), immunofluorescence, Aurora B inhibitor (ZM447439) Molecular biology of the cell High 21775627
2015 Bub1, not Zwint-1, is required for RZZ complex recruitment to kinetochores in human cells. The middle region of Bub1 (encompassing an SAC-signaling-essential domain) contributes to RZZ localization. A distinct region of Bub1 mediates kinetochore localization of BubR1 through direct binding. Thus, Bub1 coordinates checkpoint signaling via separate domains for RZZ and BubR1 recruitment. siRNA knockdown, RNAi, immunofluorescence, mutagenesis/deletion analysis of Bub1 domains Nature communications High 26031201
2015 The RZZ complex provides a separable pathway from KNL1-Bub3-Bub1 (KBB) for Mad1-Mad2 recruitment to unattached kinetochores in non-transformed diploid human cells. RZZ is necessary to recruit Mad1-Mad2 to, and delay anaphase in response to, unattached kinetochores independently of the KBB pathway. siRNA depletion, immunofluorescence, live-cell imaging in diploid RPE-1 cells Developmental cell Medium 26651294
2014 CENP-I is required to generate a stable association of the RZZ complex and Mad1 with kinetochores and inhibits their dynein-mediated removal. Aurora B regulates RZZ/Mad1 association with kinetochores. CENP-I and Aurora B constitute a molecular switch: Aurora B promotes RZZ/Mad1 loading and CENP-I inhibits their dissociation, maintaining robust spindle checkpoint signal until mature microtubule attachments are achieved. siRNA depletion, immunofluorescence, epistasis by co-depletion, live-cell imaging The Journal of cell biology Medium 24862574
2019 Polo kinase phosphorylates Spindly and impairs Spindly's ability to bind to Zwilch. This prevents dynein-mediated removal of the RZZ complex from kinetochores, delaying the formation of stable end-on attachments. Identified through an RNAi screen for suppressors of a constitutively active Polo mutant, demonstrating a genetic interaction between Polo and RZZ. RNAi screen in Drosophila, in vitro kinase assay (Polo phosphorylation of Spindly), co-immunoprecipitation (Spindly-Zwilch interaction), genetic epistasis The EMBO journal High 31849090
2019 ULK1 phosphorylates Mad1 at Ser546, promoting Mad1 kinetochore recruitment. Phosphorylation of Mad1 by ULK1 strengthens the interaction between Mad1 and the RZZ complex, which may serve as a receptor for phospho-Ser546-Mad1 at kinetochores. In vitro kinase assay, co-immunoprecipitation, site-directed mutagenesis, immunofluorescence Nucleic acids research Medium 31291454
2018 Chmp4c binds to ZW10 (component of the RZZ complex) through a small C-terminal region. Chmp4c depletion diminishes localization of RZZ and Mad1-Mad2 to prometaphase kinetochores and impairs mitotic arrest. Constitutive Chmp4c kinetochore targeting causes a ZW10-dependent checkpoint metaphase arrest, demonstrating that Chmp4c promotes spindle checkpoint signaling by promoting RZZ localization to unattached kinetochores. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, domain mapping of Chmp4c-ZW10 interaction The Journal of cell biology Medium 29362225
2019 Efficient spindle checkpoint signaling depends on the integrated activities of both Bub1 and the RZZ complex. Rod removal reduces the proximity of Bub1 and Mad1 at kinetochores. Tethering Mad1 directly to kinetochores bypasses the requirement for Rod, demonstrating that the primary role of RZZ is to localize Mad1 to generate the Mad1-Bub1 complex. Bub1 has checkpoint functions independent of Mad1 localization, consistent with a catalytic function. Genome editing (CRISPR) combined with RNAi, proximity ligation assay, rescue by forced Mad1 tethering, immunofluorescence The EMBO journal High 30782962
2023 CENP-E (kinesin-7) is required for physiological kinetochore accumulation of dynein-dynactin at the fibrous corona. When MPS1 is inhibited (preventing corona assembly), CENP-E is required to retain RZZ-Spindly at kinetochores; a phosphomimetic RZZS mutant bypasses this requirement, identifying a second receptor for polymeric RZZS. With active MPS1, CENP-E is dispensable for corona expansion but strictly required for dynein-dynactin loading. CENP-E binds directly to the RZZS complex. siRNA depletion, MPS1 inhibition, phosphomimetic mutagenesis, co-immunoprecipitation, immunofluorescence, live-cell imaging The EMBO journal High 37984321
2023 The disordered C-terminus of C. elegans Spindly (Spindly-C) interacts with both RZZ subunits ROD-1 and ZWL-1 (Zwilch ortholog) through the same two sequentially remote disordered segments, as characterized by NMR and biophysical methods. The presence of ZWL-1 in the ROD-1/ZWL-1 complex context shields or weakens the ROD-1 binding sites such that ZWL-1 is the primary direct interactor with Spindly-C in C. elegans. NMR spectroscopy, biophysical binding assays (ITC, SPR), structural characterization of disordered regions Journal of molecular biology High 33450249
2025 BUB1 and BUBR1 promote nonredundant branches of corona assembly. MPS1-dependent kinetochore docking of BUB1 initiates assembly followed by BUBR1 recruitment. CENP-E links BUBR1 to RZZ in one branch; a direct interaction between BUB1 and ROD provides a second assembly pathway. BUB1 binds directly to ROD (component of RZZ), and MAD1 recruitment to the corona fits within this BUB1-ROD interaction scheme. Biochemical reconstitution, co-immunoprecipitation, cell biology (kinetochore expansion assays), genetic depletion Science advances High 40938979
2004 Somatic mutations were found in ZWILCH/FLJ10036 in human colorectal cancers with chromosomal instability, placing ZWILCH in a pathway controlling chromosome segregation that when mutated contributes to chromosomal instability in cancer. Sequencing of colorectal cancer specimens Cancer research Low 15126332
2012 In Drosophila spermatocytes, Zwilch does not accumulate in Golgi or ER membrane compartments (in contrast to ZW10, which enriches at both Golgi and ER, and Rod, which concentrates at Golgi). zwilch mutants do not exhibit gross Golgi defects or spermatocyte cytokinesis failures, demonstrating that Zwilch is dispensable for the membrane trafficking and cytokinesis functions attributed to ZW10 and Rod in this context. Immunofluorescence, genetic mutant analysis in Drosophila spermatocytes Journal of cell science Medium 22685323

Source papers

Stage 0 corpus · 65 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Regulators of the cytoplasmic dynein motor. Nature reviews. Molecular cell biology 463 19935668
2010 Dissecting the role of MPS1 in chromosome biorientation and the spindle checkpoint through the small molecule inhibitor reversine. The Journal of cell biology 457 20624901
2005 ZW10 links mitotic checkpoint signaling to the structural kinetochore. The Journal of cell biology 214 15824131
2007 Spindly, a novel protein essential for silencing the spindle assembly checkpoint, recruits dynein to the kinetochore. The Journal of cell biology 186 17576797
2005 Rod-Zw10-Zwilch: a key player in the spindle checkpoint. Trends in cell biology 176 15922598
2008 A new mechanism controlling kinetochore-microtubule interactions revealed by comparison of two dynein-targeting components: SPDL-1 and the Rod/Zwilch/Zw10 complex. Genes & development 144 18765790
2004 Three classes of genes mutated in colorectal cancers with chromosomal instability. Cancer research 139 15126332
2018 Yes-associated protein (YAP) in pancreatic cancer: at the epicenter of a targetable signaling network associated with patient survival. Signal transduction and targeted therapy 122 29682330
2009 Mitotic control of kinetochore-associated dynein and spindle orientation by human Spindly. The Journal of cell biology 121 19468067
2014 microRNA-320/RUNX2 axis regulates adipocytic differentiation of human mesenchymal (skeletal) stem cells. Cell death & disease 119 25356868
2010 Spindly/CCDC99 is required for efficient chromosome congression and mitotic checkpoint regulation. Molecular biology of the cell 118 20427577
2015 Distinct domains in Bub1 localize RZZ and BubR1 to kinetochores to regulate the checkpoint. Nature communications 96 26031201
2018 Dynamic kinetochore size regulation promotes microtubule capture and chromosome biorientation in mitosis. Nature cell biology 95 29915359
2018 Distinct Roles of RZZ and Bub1-KNL1 in Mitotic Checkpoint Signaling and Kinetochore Expansion. Current biology : CB 89 30415700
2003 Zwilch, a new component of the ZW10/ROD complex required for kinetochore functions. Molecular biology of the cell 86 12686595
2008 Systematic analysis in Caenorhabditis elegans reveals that the spindle checkpoint is composed of two largely independent branches. Molecular biology of the cell 79 19109417
2015 KNL1-Bubs and RZZ Provide Two Separable Pathways for Checkpoint Activation at Human Kinetochores. Developmental cell 78 26651294
2018 The kinetochore proteins CENP-E and CENP-F directly and specifically interact with distinct BUB mitotic checkpoint Ser/Thr kinases. The Journal of biological chemistry 69 29748388
2018 Self-Assembly of the RZZ Complex into Filaments Drives Kinetochore Expansion in the Absence of Microtubule Attachment. Current biology : CB 64 30415699
2010 Structural analysis of the RZZ complex reveals common ancestry with multisubunit vesicle tethering machinery. Structure (London, England : 1993) 62 20462495
2008 Stable hZW10 kinetochore residency, mediated by hZwint-1 interaction, is essential for the mitotic checkpoint. The Journal of cell biology 61 18268100
2013 Spindle assembly checkpoint proteins are positioned close to core microtubule attachment sites at kinetochores. The Journal of cell biology 60 23979716
2008 SPDL-1 functions as a kinetochore receptor for MDF-1 in Caenorhabditis elegans. The Journal of cell biology 58 18936247
2019 Efficient mitotic checkpoint signaling depends on integrated activities of Bub1 and the RZZ complex. The EMBO journal 56 30782962
2017 Structure of the RZZ complex and molecular basis of its interaction with Spindly. The Journal of cell biology 55 28320825
2011 Zwint-1 is a novel Aurora B substrate required for the assembly of a dynein-binding platform on kinetochores. Molecular biology of the cell 44 21775627
2014 CENP-I and Aurora B act as a molecular switch that ties RZZ/Mad1 recruitment to kinetochore attachment status. The Journal of cell biology 42 24862574
2015 Whole-proteome genetic analysis of dependencies in assembly of a vertebrate kinetochore. The Journal of cell biology 40 26668330
2008 Unprotected Drosophila melanogaster telomeres activate the spindle assembly checkpoint. Nature genetics 36 18246067
2008 Single nucleotide polymorphisms in chromosomal instability genes and risk and clinical outcome of breast cancer: a Swedish prospective case-control study. European journal of cancer (Oxford, England : 1990) 36 19008095
2022 Structure of the RZZ complex and molecular basis of Spindly-driven corona assembly at human kinetochores. The EMBO journal 34 35373361
2011 Dynein/Dynactin-mediated transport of kinetochore components off kinetochores and onto spindle poles induced by nordihydroguaiaretic acid. PloS one 31 21305043
2018 The ESCRT protein Chmp4c regulates mitotic spindle checkpoint signaling. The Journal of cell biology 28 29362225
2018 Bub1 is not essential for the checkpoint response to unattached kinetochores in diploid human cells. Current biology : CB 25 30205061
2012 The Drosophila RZZ complex - roles in membrane trafficking and cytokinesis. Journal of cell science 25 22685323
2019 ULK1 phosphorylates Mad1 to regulate spindle assembly checkpoint. Nucleic acids research 24 31291454
2023 RZZ-Spindly and CENP-E form an integrated platform to recruit dynein to the kinetochore corona. The EMBO journal 23 37984321
2011 Spindly switch controls anaphase: spindly and RZZ functions in chromosome attachment and mitotic checkpoint control. Cell cycle (Georgetown, Tex.) 21 21252629
2016 Auxin/AID versus conventional knockouts: distinguishing the roles of CENP-T/W in mitotic kinetochore assembly and stability. Open biology 20 26791246
2015 RZZ and Mad1 dynamics in Drosophila mitosis. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 20 25772408
2019 Polo regulates Spindly to prevent premature stabilization of kinetochore-microtubule attachments. The EMBO journal 19 31849090
2018 NudE regulates dynein at kinetochores but is dispensable for other dynein functions in the C. elegans early embryo. Journal of cell science 18 29192061
2023 Multi-level functional genomics reveals molecular and cellular oncogenicity of patient-based 3' untranslated region mutations. Cell reports 17 37516102
2022 Silencing of KNTC1 inhibits hepatocellular carcinoma cells progression via suppressing PI3K/Akt pathway. Cellular signalling 15 36273753
2016 Genetic variation in the major mitotic checkpoint genes associated with chromosomal aberrations in healthy humans. Cancer letters 15 27424524
2021 Regulation of Oncogenic Targets by Tumor-Suppressive miR-150-3p in Lung Squamous Cell Carcinoma. Biomedicines 12 34944699
2018 Antagonism between the dynein and Ndc80 complexes at kinetochores controls the stability of kinetochore-microtubule attachments during mitosis. The Journal of biological chemistry 12 29475948
2023 A farnesyl-dependent structural role for CENP-E in expansion of the fibrous corona. The Journal of cell biology 10 37934467
2015 A maternal effect rough deal mutation suggests that multiple pathways regulate Drosophila RZZ kinetochore recruitment. Journal of cell science 9 25616898
2021 The Disordered Spindly C-terminus Interacts with RZZ Subunits ROD-1 and ZWL-1 in the Kinetochore through the Same Sites in C. Elegans. Journal of molecular biology 8 33450249
2018 CHMP4C: A novel regulator of the mitotic spindle checkpoint. Molecular & cellular oncology 8 30250900
2011 Evidence that the spindle assembly checkpoint does not regulate APC(Fzy) activity in Drosophila female meiosis. Genome 8 22196012
2009 The RZZ complex and the spindle assembly checkpoint. Cell structure and function 8 19420794
2020 Mutations in the Drosophila rough deal gene affecting RZZ kinetochore function. Biology of the cell 6 32602944
2024 Fibrous corona is reduced in cancer cell lines that attenuate microtubule nucleation from kinetochores. Cancer science 5 39604214
2021 Identification of estrogen receptor target genes involved in gonadal feminization caused by estrogen in Xenopus laevis. Aquatic toxicology (Amsterdam, Netherlands) 5 33515924
2015 Complex assembly, crystallization and preliminary X-ray crystallographic analysis of the human Rod-Zwilch-ZW10 (RZZ) complex. Acta crystallographica. Section F, Structural biology communications 5 25849506
2018 Cell Division: The Unattached Kinetochore Wears an Expansive RZZ Coat. Current biology : CB 3 30399347
2017 Dynein at kinetochores: Making the connection. The Journal of cell biology 3 28320823
2023 A mechanism that integrates microtubule motors of opposite polarity at the kinetochore corona. bioRxiv : the preprint server for biology 2 37163019
2025 The BUB1 and BUBR1 paralogs scaffold the kinetochore fibrous corona. Science advances 1 40938979
2026 Identification of a biologically coherent three gene immune signature predictive of immunotherapy benefit in gastric adenocarcinoma. Discover oncology 0 41832372
2026 Fidelity-Ensuring Consistency of Mitosis is Safeguarded by the 53BP1-USP28-p53 Pathway. bioRxiv : the preprint server for biology 0 41889881
2025 Distinct checkpoint and homolog biorientation pathways regulate meiosis I in Drosophila oocytes. PLoS genetics 0 39879252
2024 Distinct checkpoint and homolog biorientation pathways regulate meiosis I in Drosophila oocytes. bioRxiv : the preprint server for biology 0 39229242

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