Affinage

CDC20

Cell division cycle protein 20 homolog · UniProt Q12834

Length
499 aa
Mass
54.7 kDa
Annotated
2026-06-09
100 papers in source corpus 50 papers cited in narrative 50 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

CDC20 is the essential mitotic co-activator of the anaphase-promoting complex/cyclosome (APC/C), a WD40-repeat protein that confers substrate specificity on this E3 ubiquitin ligase to drive the metaphase-to-anaphase transition and mitotic exit (PMID:9628895, PMID:11562349). It exists in distinct cell-cycle forms — inactive MAD2-CDC20-APC at metaphase and active CDC20-APC at anaphase — and recognizes substrates directly through its N-terminus independently of the APC/C core, with the N-terminus serving as the specificity determinant (PMID:9637688, PMID:11562349). CDC20 abundance and activity are tightly periodic, peaking at M phase and falling at the M/G1 transition through proteasomal degradation and APC/C-dependent autoubiquitylation in cis (PMID:9353311, PMID:22079111). Its activity is gated by a phosphorylation switch: CDK1/cyclin A-Cdk2 phosphorylation of conserved N-terminal threonines inhibits APC/C binding, while mitotic PP2A-B56 (acting at the Apc1-loop500) and kinetochore PP1 dephosphorylate CDC20 to license APC/C loading and substrate destruction including cyclin B (PMID:22713866, PMID:26960431, PMID:32755477, PMID:31825153). The spindle assembly checkpoint restrains CDC20 by two routes — MAD2 binds a site required for APC/C association and competes with the APC/C for CDC20, and Bub1-scaffolded Plk1 phosphorylation provides an MCC-independent inhibitory mechanism (PMID:23007648, PMID:26912231); kinetochores catalyze MAD2-CDC20 (MCC) assembly through phosphorylation-dependent, geometrically constrained delivery of MAD2 and CDC20, with CDC20 itself acting as a substrate-assisted catalyst of its own incorporation (PMID:33384373, PMID:33384372, PMID:36289199). APC/C-CDC20 substrates extend across mitotic regulators (cyclin A, securin, E2F1, RAP80) and, in postmitotic and disease contexts, to Bim, p65, GSDME, LC3, p21, and SOX2, linking CDC20 to apoptosis, autophagy, osteogenic differentiation, neuronal dendrite morphogenesis, and tumor cell self-renewal (PMID:18471975, PMID:19167333, PMID:19900895, PMID:20941357, PMID:24871945, PMID:20948288, PMID:22426463, PMID:34382737). CDC20 levels are themselves set transcriptionally, being repressed by p53 under genotoxic stress and activated by FOXM1 and PRMT6, and post-translationally controlled by SPOP-Cullin3 and Parkin (PMID:17873905, PMID:26387737, PMID:27780719, PMID:25938542, PMID:36792756).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1994 Medium

    Established that the mammalian CDC20 ortholog p55CDC is a cell-cycle protein that associates, via its WD repeats, with a kinase activity peaking at M phase — the first hint that it operates within a mitotic regulatory complex.

    Evidence Immunoprecipitation, kinase assay, and immunolocalization in cycling mammalian cells

    PMID:7513050

    Open questions at the time
    • Associated kinase not identified
    • No demonstration of APC/C function or substrate
  2. 1997 Medium

    Showed CDC20 protein is cell-cycle periodic and that its destruction at M/G1 requires the 26S proteasome, tying CDC20 turnover to mitotic exit.

    Evidence Cell synchronization with proteasome inhibition and immunolocalization

    PMID:9353311

    Open questions at the time
    • Ubiquitin ligase responsible not defined
    • Mechanism of degradation (autoubiquitylation vs other) not resolved
  3. 1998 High

    Defined CDC20 as the APC/C activator whose checkpoint inhibition is mediated by MAD2, and established it as the physical bridge linking MAD2 to APC/C subunits — placing CDC20 at the heart of the spindle checkpoint.

    Evidence In vitro reconstitution with recombinant proteins, Xenopus microinjection, reciprocal co-IP of MAD2/CDC20/APC components, live imaging

    PMID:9628895 PMID:9637688 PMID:9736712

    Open questions at the time
    • Structural basis of MAD2-CDC20 binding undefined
    • How CDC20 selects substrates not yet shown
  4. 2001 High

    Resolved how CDC20 confers substrate specificity, showing its N-terminus binds APC/C substrates directly and independently of the APC/C core.

    Evidence In vitro binding, chimeric proteins, and ubiquitination assays without APC/C

    PMID:11562349

    Open questions at the time
    • Full repertoire of recognition motifs (D-box vs KEN) not enumerated here
    • Role of WD40 domain in substrate binding addressed only later
  5. 2003 High

    Established that CDK/MAPK phosphorylation of CDC20 does not block APC/C activation per se but controls its affinity for checkpoint proteins, defining CDC20 phosphorylation as the substrate of checkpoint control.

    Evidence In vitro kinase and APC/C assays with phospho-site mutagenesis in Xenopus extracts

    PMID:12855955

    Open questions at the time
    • Counteracting phosphatase not identified at this stage
    • Precise residues governing each checkpoint-protein interaction not fully mapped
  6. 2008 High

    Explained how cyclin A is degraded despite an active checkpoint, showing CDC20 binds cyclin A with little associated Mad2 to permit checkpoint-independent destruction.

    Evidence Reciprocal co-IP, in vitro ubiquitination, and RNAi with synchronization

    PMID:18471975

    Open questions at the time
    • Structural basis for Cks-dependent recognition unresolved
    • Why cyclin A escapes checkpoint while cyclin B does not only partially explained
  7. 2009 High

    Extended CDC20-APC function beyond mitosis into postmitotic neurons, showing centrosomal CDC20-APC controls dendrite morphogenesis and degrades NeuroD2 to drive presynaptic differentiation.

    Evidence In vivo knockdown in rat cerebellum, live imaging, ubiquitination assays, and genetic epistasis

    PMID:19167333 PMID:19900895

    Open questions at the time
    • How CDC20-APC is activated in postmitotic cells lacking cell-cycle cues unclear
    • Full neuronal substrate set undefined
  8. 2012 High

    Dissected the two-pronged regulation of CDC20: CDK phosphorylation of N-terminal threonines blocks APC/C binding while mitotic PP2A removes them, and MAD2 directly competes with APC/C for CDC20 — defining the phosphorylation switch and a non-pseudosubstrate checkpoint mechanism.

    Evidence In vitro kinase/phosphatase assays, Xenopus extracts, competition binding, and in vivo checkpoint mutagenesis

    PMID:22713866 PMID:23007648

    Open questions at the time
    • Identity of the in vivo kinetochore phosphatase not yet pinned
    • Coordination between MAD2 competition and phospho-control not integrated
  9. 2012 High

    Identified APC15 as the subunit enabling APC/C(MCC)-dependent CDC20 autoubiquitylation that drives MCC disassembly, providing the mechanism for checkpoint silencing.

    Evidence RNAi depletion and in vitro ubiquitylation with reconstituted human APC/C

    PMID:22079111 PMID:23007861

    Open questions at the time
    • How substrate levels tune the autoubiquitylation/disassembly balance not fully quantified
    • Structural arrangement at the MCC-binding site addressed only later
  10. 2016 High

    Revealed an MCC-independent checkpoint mechanism in which Bub1 directly and Plk1-scaffolded phosphorylation of CDC20 inhibits APC/C(CDC20), and showed interphase cyclin A2-Cdk2 phosphorylation of CDC20 sets the timing of mitotic entry.

    Evidence In vitro kinase and APC/C inhibition assays, phospho-mutagenesis with RNAi in human cells, and genetic rescue with non-degradable cyclin A2

    PMID:26912231 PMID:26960431

    Open questions at the time
    • Relative contribution of MCC vs Bub1-Plk1 phosphorylation in vivo not quantified
    • Crosstalk between interphase and mitotic phospho-control unresolved
  11. 2017 High

    Showed that APC/C activation and inhibition both depend on CDC20 fluxing through a single kinetochore site, with PP1 dephosphorylation directing CDC20 toward APC/C activation and microtubule attachment status setting the balance.

    Evidence Live imaging with kinase/phosphatase inhibitors and RNAi in C. elegans and human cells

    PMID:28698300

    Open questions at the time
    • Molecular determinant that switches CDC20 fate at the shared site not fully defined
  12. 2020 High

    Mapped the phosphatases that license CDC20-APC/C loading, showing PP2A-B56 binds the Apc1-loop500 to dephosphorylate CDC20 and PP1 removes N-terminal inhibitory phosphorylation to permit cyclin B destruction at anaphase.

    Evidence Reconstituted APC/C in Xenopus extracts, PP1 depletion/inhibition, and CDC20 phospho-mutant rescue

    PMID:31825153 PMID:32755477

    Open questions at the time
    • Spatial coordination of PP1 vs PP2A-B56 action on CDC20 not integrated
    • How phosphatase activity is locally controlled at kinetochores unresolved
  13. 2021 High

    Provided the mechanism of kinetochore-catalyzed MCC assembly, showing CDC20 is a substrate-assisted catalyst whose own multi-site docking and phosphorylation-dependent geometric constraints prime MAD2 capture.

    Evidence Reconstituted SAC/kinetochore systems with purified components, conformational analysis, live-cell probes, and phospho-mutagenesis

    PMID:33384372 PMID:33384373

    Open questions at the time
    • Full structural intermediate of the assembly reaction not solved
    • Kinetics of catalysis in living cells only inferred
  14. 2021 High

    Broadened CDC20 substrate biology into differentiation and cell death, establishing WD40-mediated degradation of NF-kB p65 in osteogenesis with an in vivo bone phenotype.

    Evidence Co-IP with domain mapping, APC11-dependent ubiquitination assays, and conditional knockout mice

    PMID:34382737

    Open questions at the time
    • How CDC20-APC is engaged in non-dividing osteoblasts not detailed
    • Relationship to mitotic CDC20 regulation unclear
  15. 2023 High

    Uncovered an additional layer of CDC20 control: alternative translational isoforms (e.g. Met43) lacking N-terminal SAC sites resist checkpoint inhibition and act as a molecular timer for mitotic slippage, and a conserved Bub1-Plk1/ABBA pathway recruits CDC20 to kinetochores independent of the checkpoint.

    Evidence Ribosome profiling, isoform-specific and CRISPR engineering with SAC assays; C. elegans genetics and live imaging with phospho-mutagenesis

    PMID:37100900 PMID:37137308

    Open questions at the time
    • Physiological triggers selecting isoform usage not defined
    • How checkpoint-independent kinetochore recruitment integrates with MCC formation unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CDC20's many non-mitotic substrates and its transcriptional/post-translational regulators are coordinated across distinct cell types, and the structural basis for switching between substrate ubiquitylation and self-inhibition, remain to be integrated.
  • No unified model linking mitotic vs postmitotic CDC20 activation
  • Many cancer-context substrates rest on single-lab Co-IP/knockdown without reconstitution
  • Direct E3 ligase mechanism for several non-canonical substrates not biochemically resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 2 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 1 GO:0005815 microtubule organizing center 1 GO:0005829 cytosol 1 GO:0005856 cytoskeleton 1
Pathway
R-HSA-1640170 Cell Cycle 6 R-HSA-392499 Metabolism of proteins 6 R-HSA-1266738 Developmental Biology 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-9612973 Autophagy 1
Partners
AURKABUB1BUBR1CDC27MAD1MAD2PP1PP2A-B56
Complex memberships
APC/CMitotic checkpoint complex (MCC)

Evidence

Reading pass · 50 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 hMAD2 forms a ternary hMAD2-CDC20-APC complex that inhibits APC ubiquitin ligase activity. Only the MAD2 tetramer (not monomer) inhibits APC activation, demonstrating that MAD2 binding alone is insufficient for inhibition and that MAD2 oligomeric state matters. Three forms of mitotic APC were identified: inactive MAD2-CDC20-APC at metaphase, active CDC20-APC at anaphase, and CDH1-APC in G1. In vitro reconstitution with recombinant proteins, Xenopus embryo microinjection, immunoprecipitation Genes & development High 9637688
1998 Mammalian p55CDC (CDC20) localizes to kinetochores from late prophase to telophase, to spindle microtubules and poles, and to the cytoplasm. In M-phase (but not interphase) extracts, p55CDC co-immunoprecipitates with APC components CDC27 and CDC16, and with MAD2. p55CDC is required for the association of MAD2 with CDC27 and CDC16, acting as a bridge between MAD2 and the APC/C. Immunofluorescence, GFP chimera live imaging, co-immunoprecipitation from HeLa cell extracts, antibody microinjection The Journal of cell biology High 9628895
1994 p55CDC (CDC20) is expressed in cycling mammalian cells and is phosphorylated during cell division. Immunoprecipitates of p55CDC contain associated kinase activity that fluctuates during the cell cycle (peaking at M phase), indicating p55CDC associates with a cell cycle-regulated kinase complex via its seven WD repeats. Immunoprecipitation, kinase assay, antisense transfection, immunolocalization Molecular and cellular biology Medium 7513050
1997 p55CDC protein levels are highest at M phase and lowest in G1. Its degradation at the M/G1 transition is mediated by the 26S proteasome (inhibition of the proteasome prevents both mitotic exit and loss of p55CDC). Dynamic changes in p55CDC localization occur as cells transit mitosis. Cell synchronization, proteasome inhibitor treatment, immunolocalization, Western blot The Journal of biological chemistry Medium 9353311
1998 MAD2 associates with the APC component CDC27 transiently during early normal mitosis (not only upon checkpoint activation), and this association requires p55CDC (CDC20), forming a MAD2/p55CDC/CDC27 ternary complex. A MAD2/CDC27 complex that forms independently of p55CDC was also detected. Co-immunoprecipitation from mammalian cells at different cell cycle stages Proceedings of the National Academy of Sciences of the United States of America Medium 9736712
2001 CDC20 (and CDH1) directly bind APC/C substrates via their N-termini, independent of APC/C. The N-terminus of CDC20 confers substrate specificity. Active chimeras swapping N-termini demonstrate that the N-terminus is the specificity determinant for substrate recognition. In vitro binding assays, chimeric protein construction, ubiquitination assays in the absence of APC/C Genes & development High 11562349
2003 Xenopus CDC20 is phosphorylated at Ser50, Thr64, Thr68, and Thr79 during mitosis; MAPK contributes to phosphorylation at Thr64 or Thr68. Phosphorylation-deficient CDC20 mutants activate APC/C normally but fail to respond to spindle checkpoint signals due to reduced affinity for spindle checkpoint proteins (BubR1, Bub3, Mad2). Thus, the spindle checkpoint arrests cells by inhibiting fully-phosphorylated CDC20. In vitro kinase assays, Xenopus egg extract APC/C ubiquitination assays, phospho-site mutagenesis, checkpoint binding assays Nature cell biology High 12855955
2004 In budding yeast, the PKA pathway supports Chk1 in restraining anaphase by phosphorylating Cdc20 on PKA consensus sites after DNA damage. This phosphorylation requires Mec1 (ATR ortholog) and PKA catalytic subunits Tpk1/Tpk2. Phosphorylation-defective Cdc20 mutants accelerate securin and Clb2 destruction and allow Cdc20 to interact with Clb2 under checkpoint conditions. Genetic epistasis, phospho-site mutagenesis, in vivo degradation assays, co-immunoprecipitation in yeast Nature cell biology High 14743219
2008 CDC20 is rate-limiting for cyclin A destruction and binds cyclin A efficiently before and during mitosis. The cyclin A-CDC20 complex has little associated Mad2, enabling spindle-checkpoint-independent cyclin A degradation. Cks protein binding to the cyclin A complex is additionally required for its checkpoint-independent degradation by APC/C-CDC20. Co-immunoprecipitation, in vitro ubiquitination assays, RNA interference, cell synchronization Molecular cell High 18471975
2009 CDC20-APC plays an essential role in dendrite morphogenesis in postmitotic neurons. CDC20 is enriched at the centrosome in neurons, and centrosomal localization is critical for this function. HDAC6 promotes polyubiquitination of CDC20, stimulates centrosomal CDC20-APC activity, and drives dendrite differentiation. Knockdown in cerebellar slices and in vivo in rats, live imaging for centrosomal localization, ubiquitination assays Cell High 19167333
2009 CDC20-APC triggers degradation of the transcription factor NeuroD2 to promote presynaptic differentiation in postmitotic neurons. NeuroD2's target gene Complexin II mediates its suppression of presynaptic differentiation. Knockdown in primary neurons and rat cerebellar cortex in vivo, ubiquitination assays, genetic epistasis Science High 19900895
1999 CDC20 associates with the kinase Aurora2/Aik in HeLa cells. CDC20-associated MBP kinase activity peaks in early M phase (embryonic cells) or G2 phase (somatic cells). The association suggests that Aurora2/Aik carries out or regulates some CDC20 function. Co-immunoprecipitation from HeLa cells, kinase assay with MBP substrate Proceedings of the National Academy of Sciences of the United States of America Medium 10377410
2000 CDC20 (p55CDC) directly interacts with BUBR1 as shown by yeast two-hybrid, GST pulldown, and co-immunoprecipitation. BUBR1 phosphorylates p55CDC in vitro, and this phosphorylation correlates with spindle checkpoint activation. Spindle checkpoint activation by nocodazole enhances the p55CDC-BUBR1 association. Yeast two-hybrid, GST pulldown, co-immunoprecipitation from HeLa cells, in vitro kinase assay Oncogene High 11030144
2007 p53 transcriptionally represses CDC20 expression through binding to a consensus p53-binding site in the CDC20 promoter and through CDE/CHR elements. This repression occurs in response to genotoxic stress in a p53- and p21-dependent manner. siRNA-mediated silencing of p53 induces CDC20 expression in normal human dermal fibroblasts. Reporter assays, ChIP, siRNA knockdown, expression analysis after genotoxic stress Oncogene Medium 17873905
2009 p53 binds directly to a consensus site in the CDC20 promoter and causes chromatin remodeling to repress CDC20 transcription. p53 also downregulates CDC20 through CDE/CHR elements in a p21-independent manner under p53-overexpression conditions. The CCAAT elements in the CDC20 promoter are not used by p53 for repression. ChIP, promoter reporter assay, chromatin remodeling analysis, p53 binding site mutagenesis Nucleic acids research Medium 19273532
2010 Cdc20 is critical for meiosis I in female mice. Cdc20 hypomorphic females produce aneuploid gametes due to chromosome lagging and misalignment during meiosis I. Cyclin B1, cyclin A2, and securin are inefficiently degraded in metaphase I, and anaphase I onset is markedly delayed, demonstrating Cdc20's role in APC/C activation during female meiosis. Hypomorphic mouse model, chromosome analysis, immunostaining, live oocyte imaging PLoS genetics High 20941357
2011 CDC20 undergoes APC/C-dependent autoubiquitination in cis (intramolecular mechanism) while bound to its activator-binding site on the APC/C core, independent of Cdc20's C-box. This cell-cycle-regulated mechanism contributes to the decline of CDC20 levels after anaphase. High substrate levels in vitro reduce Cdc20 autoubiquitination. In vitro ubiquitination assays, cell cycle synchronization, mutagenesis Current biology High 22079111
2012 APC15 is required for APC/C(MCC)-dependent CDC20 autoubiquitylation and degradation, and for timely anaphase initiation. APC15 is located near the APC/C MCC-binding site and is dispensable for substrate ubiquitylation by APC/C(CDC20) or APC/C(CDH1). CDC20 autoubiquitylation promotes MCC disassembly. RNAi depletion, in vitro ubiquitylation assays with recombinant human APC/C, cell biology Nature structural & molecular biology High 23007861
2012 Mad2 inhibits CDC20 by binding directly to a site required for CDC20 to bind the APC/C. Mad2 and the APC/C compete for CDC20 in vitro, and a CDC20 mutant that does not bind stably to Mad2 abrogates the SAC in vivo. This reveals a second mechanism by which SAC inhibits APC/C (beyond pseudosubstrate inhibition). In vitro competition binding assay, mutagenesis, in vivo checkpoint assay The Journal of cell biology High 23007648
2012 CDC20 is phosphorylated at six conserved residues (S50/T64/T68/T79/S114/S165) by CDK in Xenopus extracts. When threonine residues are phosphorylated, CDC20 binding to and activation of APC/C are inhibited. PP2A (active in mitosis) specifically dephosphorylates these threonine residues to activate APC/C. The 'activation domain' of CDC20 associates with APC/C subunits Apc6 and Apc8. In vitro kinase/phosphatase assays, Xenopus egg extracts, phospho-mutagenesis, co-immunoprecipitation The EMBO journal High 22713866
2014 APC/C-CDC20 ubiquitinates the pro-apoptotic BH3-only protein Bim, targeting it for proteasomal degradation. Cdc20 depletion sensitizes cells to apoptotic stimuli by stabilizing Bim. Tax viral oncoprotein elevates APC/C(CDC20) activity to reduce Bim levels and confer apoptotic resistance. siRNA screen, ubiquitination assay, co-immunoprecipitation, in vitro degradation assay Developmental cell High 24871945
2015 Parkin (E3 ubiquitin ligase) interacts with CDC20 and CDH1 to mediate degradation of mitotic regulators independent of APC/C. Parkin is phosphorylated and activated by Plk1 during mitosis. Parkin deficiency causes overexpression of its substrates, mitotic defects, genomic instability, and tumorigenesis. Co-immunoprecipitation, ubiquitination assay, kinase assay, genetic knockout Molecular cell High 26387737
2016 Bub1 directly phosphorylates CDC20, and also scaffolds Plk1-mediated phosphorylation of CDC20. Bub1-Plk1-dependent Cdc20 phosphorylation inhibits APC/C(CDC20) in vitro and is required for spindle checkpoint signalling in human cells. This phosphorylation is regulated by upstream checkpoint signals and is dispensable for MCC assembly. A phospho-mimicking CDC20 mutant can restore nocodazole-induced mitotic arrest in Mad2- or BubR1-depleted cells. In vitro kinase assay, APC/C ubiquitination assay, phospho-mutagenesis, RNAi in human cells Nature communications High 26912231
2016 SPOP (Cullin3 adaptor) directly interacts with CDC20 via its degron and promotes CDC20 polyubiquitination and degradation. Cullin3 (but not Cullin1) specifically interacts with and degrades CDC20. Prostate cancer-derived SPOP mutants fail to bind CDC20 and promote its degradation, resulting in elevated CDC20. Co-immunoprecipitation, ubiquitination assay, half-life assay, MLN4924 pharmacological inhibition Cancer letters Medium 27780719
2016 Cyclin A2-Cdk2 binds and phosphorylates CDC20 during interphase, inhibiting APC/C-CDC20 activity. Preventing CDC20 phosphorylation results in premature APC/C-CDC20 activation and destabilization of cyclin B1 and A2, lengthening G2 and slowing mitotic entry. Expressing non-degradable cyclin A2 (but not cyclin B1) restores mitotic entry. Co-immunoprecipitation, in vitro kinase assay, phospho-mutagenesis, cell synchronization Nature communications High 26960431
2017 Kinetochore-localized PP1 dephosphorylates CDC20, directing it toward APC/C activation and promoting mitotic exit. Both APC/C activation and inhibition depend on CDC20 fluxing through the same kinetochore binding site; the microtubule attachment status controls the balance between these opposing CDC20 fates. Live imaging, kinase/phosphatase inhibitor experiments, RNAi in C. elegans and human cells Genes & development High 28698300
2011 CDC20 transcriptionally activates expression of the E2 ubiquitin-conjugating enzyme UbcH10 via its WD40 domain. CDC20 physically interacts with APC/C-CBP/p300 complex, and this complex is recruited to the UBCH10 promoter to drive transcription. This activity is cell cycle-specific. Reporter assay, co-immunoprecipitation, ChIP, WD40 domain mutagenesis The Journal of biological chemistry Medium 21454660
2010 APC/C(CDC20) targets E2F1 for degradation in prometaphase. Ectopic expression of CDC20 reduces E2F1 protein levels; CDC20 knockdown stabilizes E2F1 and leads to its accumulation in prometaphase cells. Co-expression of DP1 with E2F1 blocks APC/C-induced E2F1 degradation. Co-expression experiments, siRNA knockdown, cell synchronization, ubiquitination assay Cell cycle Medium 20948288
2012 RAP80 is polyubiquitinated and degraded by APC/C(CDC20) in mitosis (and by APC/C(CDH1) in G1). Knockdown of CDC20 blocks RAP80 degradation during mitosis. A conserved D-box in RAP80 is required for its ubiquitination and stability control by APC/C(CDC20). siRNA knockdown, ubiquitination assay, D-box mutagenesis, cell cycle synchronization Molecular cancer research Medium 22426463
2019 CDC20 promotes degradation of Axin1 (core member of the β-catenin destruction complex) via its E3 ligase activity, reducing β-catenin phosphorylation and promoting β-catenin nuclear translocation and transcriptional activity in prostate cancer stem-like cells. siRNA knockdown, Western blot for downstream signaling, sphere formation and tumorigenicity assays EBioMedicine Medium 30904606
2020 APC/C(CDC20) binds to the D-box motif in PHD3 protein and promotes its polyubiquitination and degradation, thereby stabilizing HIF-1α and promoting VEGF secretion in hepatocellular carcinoma cells. Co-immunoprecipitation, ubiquitination assay, CDC20 knockdown/pharmacological inhibition, PHD3 D-box mutagenesis Cancer letters Medium 33039559
2018 CDC20 directly targets LC3 (a key autophagy regulator) for ubiquitination and proteasomal degradation, thereby inhibiting autophagy and promoting cardiac hypertrophy. Co-immunoprecipitation, ubiquitination assay, rAAV9-mediated cardiac overexpression/knockdown in vivo, in vitro cardiomyocyte assays Theranostics Medium 30613277
2021 CDC20 specifically interacts with GSDME via its degron and promotes GSDME ubiquitination and proteasomal degradation in a degron-dependent manner, thereby suppressing pyroptosis in prostate cancer cells. Immunoprecipitation, ubiquitination assay, siRNA knockdown, cycloheximide chase assay, in vivo syngeneic mouse models Experimental hematology & oncology Medium 37528490
2021 CDC20 (via its WD40 domain) interacts with the DNA-binding domain of p65 (NF-κB subunit) and promotes APC11-dependent ubiquitination and degradation of p65 to promote osteogenic differentiation. Cdc20 conditional knockout mice display decreased bone formation. Co-immunoprecipitation, ubiquitination assay, domain mapping, conditional knockout mouse model EMBO reports High 34382737
2021 CDC20 assists its own catalytic incorporation into the mitotic checkpoint complex (MCC) as a substrate-assisted catalyst. Simultaneous docking on several sites of the catalytic kinetochore complex is required for CDC20 to access MAD2. The catalyst promotes MCC assembly through spatially and temporally coordinated conformational changes in both MAD2 and CDC20. Reconstituted SAC system, biochemical analysis with purified components, structural/conformational analysis Science High 33384373
2021 Kinetochore-catalyzed MAD2-CDC20 assembly occurs through a tripartite mechanism: localized delivery of MAD2 and CDC20 substrates plus two phosphorylation-dependent interactions that geometrically constrain their positions and prime CDC20 for MAD2 interaction. Reconstituted kinetochore system, live-cell probe for Mad2-Cdc20 assembly, epistasis with phospho-mutants Science High 33384372
2020 PP1 removes specific inhibitory phosphorylation in the N-terminus of CDC20 to promote APC/C(CDC20)-dependent cyclin B destruction at anaphase onset. Depletion or chemical inhibition of PP1 stabilizes cyclin B and delays metaphase-to-anaphase transition. CDC206A (CDK1 phosphorylation-defective) mutant cells rapidly destroy cyclin B and enter anaphase without PP1 activity. PP1 depletion/inhibition, phospho-mutagenesis (CDC206A), cell biology, cyclin B stability assay Molecular biology of the cell High 32755477
2019 PP2A-B56 directly binds the disordered Apc1-loop500 domain of APC/C and stimulates CDC20 loading onto APC/C by dephosphorylating CDC20. Mutations in Apc1-loop500 abolishing B56 binding decrease CDC20 loading and APC/C-dependent ubiquitylation. A non-phosphorylatable CDC20 mutant bypasses the need for PP2A-B56. APC/C reconstitution in Xenopus egg extracts, mutagenesis, co-immunoprecipitation, in vitro ubiquitylation assay EMBO reports High 31825153
2022 Mps1-phosphorylated Mad1 CTD creates a phosphorylation-specific interaction with CDC20. Together with Mps1-phosphorylation of Bub1, this generates a tripartite assembly of Bub1 and CDC20 onto the C-terminal domain of Mad1, positioning the Mad2-interacting motif (MIM) of CDC20 near open-Mad2 to catalyse formation of C-MAD2:CDC20. Structural analysis (NMR, cross-linking MS), biochemical binding assays, mutagenesis Nature communications High 36289199
2023 Human cells express conserved alternative CDC20 translational isoforms initiated at downstream AUGs (e.g., Met43). The truncated Met43 isoform lacks key N-terminal SAC inhibitory binding sites and is resistant to SAC-mediated inhibition, promoting mitotic exit even in the presence of mitotic perturbations. Differential turnover of full-length vs. truncated isoforms during prolonged arrest creates a molecular timer controlling mitotic slippage duration. Isoform-specific mutagenesis, ribosome profiling, cell synchronization, SAC assays, CRISPR engineering Nature High 37100900
2023 BUB-1-bound PLK-1 phosphorylates the ABBA motif of BUB-1 to promote BUB-1-CDC-20 interaction and CDC-20 kinetochore recruitment. This PLK-1 kinase activity at kinetochores is required for CDC-20 localization to kinetochores and timely mitotic progression in C. elegans embryos, functioning in a checkpoint-independent manner. C. elegans genetics, live imaging, phospho-mutagenesis, kinase inhibitor experiments Current biology High 37137308
2018 PPM1K (mitochondrial phosphatase regulating BCAA catabolism) maintains MEIS1 and p21 levels by decreasing CDC20-mediated ubiquitination and degradation. PPM1K deficiency leads to increased CDC20-dependent degradation of MEIS1 and p21, reducing HSC glycolysis and quiescence. Co-immunoprecipitation, ubiquitination assay, genetic knockout in mice, fluorescent BCAA sensor Cell reports Medium 29719258
2015 CDC20-APC drives invasiveness and self-renewal in glioblastoma stem-like cells (GSCs) through degradation of the pluripotency transcription factor SOX2. shRNA knockdown, overexpression, orthotopic xenograft, Western blot for SOX2 levels Cell reports Medium 26074073
2015 CDC20 maintains glioblastoma tumor initiating cells (TICs) through APC/C-dependent degradation of p21(CIP1/WAF1). CDC20 disruption stabilizes p21, repressing CDC25C, c-Myc, and Survivin. FOXM1 transcriptionally controls CDC20 expression in TICs. RNAi knockdown, ubiquitination assay, ChIP for FOXM1 at CDC20 promoter, chromatin analysis Oncotarget Medium 25938542
2020 CDC20 directly interacts with Mcl-1 (anti-apoptotic Bcl-2 family member), and this interaction is required for Mcl-1 stability. Knockdown of CDC20 suppresses Mcl-1 expression, inhibits p-Chk1, impairs Rad51-mediated DNA repair, and induces apoptosis in colorectal cancer cells. Co-immunoprecipitation, GST pulldown assay, siRNA knockdown, in vivo radiosensitization study International journal of molecular sciences Medium 32932732
2009 Cdc20 and PC-PLC co-immunoprecipitate and co-localize in the perinuclear endoplasmic reticulum (JUNQ compartment) in rat hepatoma cells. Cdc20 overexpression alters PC-PLC subcellular localization and causes its degradation via the ubiquitin-proteasome pathway, demonstrating APC/C(Cdc20) targets PC-PLC. Co-immunoprecipitation, confocal microscopy co-localization, overexpression, proteasome inhibitor experiment Journal of cellular biochemistry Low 19347873
2006 A second Mad2-binding domain on CDC20 was identified in amino acids 342-355 within the WD repeat region. An intervening region between this domain and the previously known N-terminal domain (aa 111-150) interferes with Mad2 binding when either domain is present alone. Optimal Mad2 binding requires coordination of three domains. A polyhistidine motif adjacent to the second binding domain may maintain CDC20 conformation for Mad2 binding. Co-immunoprecipitation and co-localization with CDC20 deletion mutants, peptide inhibition assay The Biochemical journal Medium 16497171
2021 Cdc20 downregulation or APC/C inhibition induces premature senescence in normal lung fibroblasts through GSK-3β-mediated phosphorylation and downregulation of securin. In NSCLC cells (which bypass senescence), the same pathway induces apoptosis through securin downregulation. siRNA knockdown, APC/C pharmacological inhibitor, GSK-3β inhibitor rescue, Western blot for securin phosphorylation The Journal of biological chemistry Medium 35988650
2010 In Drosophila, BubR1 (but not Mad2) is required for CDC20 recruitment to kinetochores. BubR1 and Mad2 can bind CDC20 independently, and their interactions are enhanced during mitotic arrest. This demonstrates that BubR1 provides the primary kinetochore-CDC20 recruitment mechanism in flies. RNAi in Drosophila S2 cells and syncytial embryos, live imaging, co-immunoprecipitation Molecular and cellular biology Medium 20421417
2023 PRMT6 maintains CDC20 transcription via H3R2me2a histone methylation at the CDC20 promoter. CDC20 in turn interacts with CDKN1B (p27) and destabilizes it via ubiquitin-mediated degradation, promoting GBM cell proliferation. ChIP-qPCR for PRMT6/H3R2me2a at CDC20 promoter, co-immunoprecipitation for CDC20-CDKN1B, ubiquitination assay, rescue experiments Oncogene Medium 36792756

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation. Genes & development 508 9637688
2007 Cdc20: a WD40 activator for a cell cycle degradation machine. Molecular cell 301 17612486
2002 Regulation of APC-Cdc20 by the spindle checkpoint. Current opinion in cell biology 289 12473343
1998 Mammalian p55CDC mediates association of the spindle checkpoint protein Mad2 with the cyclosome/anaphase-promoting complex, and is involved in regulating anaphase onset and late mitotic events. The Journal of cell biology 223 9628895
2001 Substrate recognition by the Cdc20 and Cdh1 components of the anaphase-promoting complex. Genes & development 203 11562349
2015 Targeting Cdc20 as a novel cancer therapeutic strategy. Pharmacology & therapeutics 202 25850036
2007 CDC20, a potential cancer therapeutic target, is negatively regulated by p53. Oncogene 185 17873905
2009 A centrosomal Cdc20-APC pathway controls dendrite morphogenesis in postmitotic neurons. Cell 165 19167333
2008 Cdc20 and Cks direct the spindle checkpoint-independent destruction of cyclin A. Molecular cell 160 18471975
2014 Increased CDC20 expression is associated with development and progression of hepatocellular carcinoma. International journal of oncology 133 25069850
2014 Cdc20 and securin overexpression predict short-term breast cancer survival. British journal of cancer 132 24853182
2003 Phosphorylation of Cdc20 is required for its inhibition by the spindle checkpoint. Nature cell biology 132 12855955
2014 APC(Cdc20) suppresses apoptosis through targeting Bim for ubiquitination and destruction. Developmental cell 125 24871945
2017 Cdc20: At the Crossroads between Chromosome Segregation and Mitotic Exit. Trends in biochemical sciences 124 28202332
1997 Cell cycle-regulated expression, phosphorylation, and degradation of p55Cdc. A mammalian homolog of CDC20/Fizzy/slp1. The Journal of biological chemistry 120 9353311
2012 APC15 mediates CDC20 autoubiquitylation by APC/C(MCC) and disassembly of the mitotic checkpoint complex. Nature structural & molecular biology 119 23007861
1998 Mad2 transiently associates with an APC/p55Cdc complex during mitosis. Proceedings of the National Academy of Sciences of the United States of America 114 9736712
1994 A novel mammalian protein, p55CDC, present in dividing cells is associated with protein kinase activity and has homology to the Saccharomyces cerevisiae cell division cycle proteins Cdc20 and Cdc4. Molecular and cellular biology 110 7513050
2012 Increased CDC20 expression is associated with pancreatic ductal adenocarcinoma differentiation and progression. Journal of hematology & oncology 108 22475564
2009 A Cdc20-APC ubiquitin signaling pathway regulates presynaptic differentiation. Science (New York, N.Y.) 105 19900895
1999 Identification of frequent impairment of the mitotic checkpoint and molecular analysis of the mitotic checkpoint genes, hsMAD2 and p55CDC, in human lung cancers. Oncogene 105 10439037
2013 Cdc20: a potential novel therapeutic target for cancer treatment. Current pharmaceutical design 98 23151139
2016 The Bub1-Plk1 kinase complex promotes spindle checkpoint signalling through Cdc20 phosphorylation. Nature communications 93 26912231
2015 A CDC20-APC/SOX2 Signaling Axis Regulates Human Glioblastoma Stem-like Cells. Cell reports 92 26074073
2012 Dephosphorylation of Cdc20 is required for its C-box-dependent activation of the APC/C. The EMBO journal 88 22713866
2021 CDC20 regulates the cell proliferation and radiosensitivity of P53 mutant HCC cells through the Bcl-2/Bax pathway. International journal of biological sciences 86 34512169
2010 Cdc20 is critical for meiosis I and fertility of female mice. PLoS genetics 85 20941357
2004 The DNA damage checkpoint and PKA pathways converge on APC substrates and Cdc20 to regulate mitotic progression. Nature cell biology 80 14743219
2015 Parkin Regulates Mitosis and Genomic Stability through Cdc20/Cdh1. Molecular cell 79 26387737
1997 A fission yeast homolog of CDC20/p55CDC/Fizzy is required for recovery from DNA damage and genetically interacts with p34cdc2. Molecular and cellular biology 77 9001228
2019 Cell division cycle 20 (CDC20) drives prostate cancer progression via stabilization of β-catenin in cancer stem-like cells. EBioMedicine 74 30904606
2012 Mad2 and the APC/C compete for the same site on Cdc20 to ensure proper chromosome segregation. The Journal of cell biology 67 23007648
2005 Low concentrations of taxol cause mitotic delay followed by premature dissociation of p55CDC from Mad2 and BubR1 and abrogation of the spindle checkpoint, leading to aneuploidy. Cell cycle (Georgetown, Tex.) 62 16138009
2021 CDC20 assists its catalytic incorporation in the mitotic checkpoint complex. Science (New York, N.Y.) 61 33384373
2020 APCCDC20-mediated degradation of PHD3 stabilizes HIF-1a and promotes tumorigenesis in hepatocellular carcinoma. Cancer letters 60 33039559
2018 PPM1K Regulates Hematopoiesis and Leukemogenesis through CDC20-Mediated Ubiquitination of MEIS1 and p21. Cell reports 60 29719258
1999 Cdc20 associates with the kinase aurora2/Aik. Proceedings of the National Academy of Sciences of the United States of America 59 10377410
2019 CDC20 associated with cancer metastasis and novel mushroom‑derived CDC20 inhibitors with antimetastatic activity. International journal of oncology 58 31081056
2017 Kinetochores accelerate or delay APC/C activation by directing Cdc20 to opposing fates. Genes & development 56 28698300
2000 p55CDC/hCDC20 is associated with BUBR1 and may be a downstream target of the spindle checkpoint kinase. Oncogene 55 11030144
2016 Interphase APC/C-Cdc20 inhibition by cyclin A2-Cdk2 ensures efficient mitotic entry. Nature communications 52 26960431
2015 CDC20 maintains tumor initiating cells. Oncotarget 51 25938542
2018 Cdc20 inhibitor apcin inhibits the growth and invasion of osteosarcoma cells. Oncology reports 50 29901174
2018 CDC20 regulates cardiac hypertrophy via targeting LC3-dependent autophagy. Theranostics 48 30613277
2010 APC/C(Cdc20) targets E2F1 for degradation in prometaphase. Cell cycle (Georgetown, Tex.) 48 20948288
2022 Targeting Cdc20 for cancer therapy. Biochimica et biophysica acta. Reviews on cancer 47 36243246
2021 A tripartite mechanism catalyzes Mad2-Cdc20 assembly at unattached kinetochores. Science (New York, N.Y.) 47 33384372
2016 Prostate cancer-associated mutation in SPOP impairs its ability to target Cdc20 for poly-ubiquitination and degradation. Cancer letters 46 27780719
2009 DNA damage induced p53 downregulates Cdc20 by direct binding to its promoter causing chromatin remodeling. Nucleic acids research 46 19273532
2023 Alternative CDC20 translational isoforms tune mitotic arrest duration. Nature 45 37100900
2015 CYP1B1 promotes tumorigenesis via altered expression of CDC20 and DAPK1 genes in renal cell carcinoma. BMC cancer 44 26626260
2021 Inhibition of Cdc20 suppresses the metastasis in triple negative breast cancer (TNBC). Breast cancer (Tokyo, Japan) 40 33813687
2011 Ubiquitination of Cdc20 by the APC occurs through an intramolecular mechanism. Current biology : CB 40 22079111
2019 Elevated signature of a gene module coexpressed with CDC20 marks genomic instability in glioma. Proceedings of the National Academy of Sciences of the United States of America 38 30877245
2023 Inhibition of CDC20 potentiates anti-tumor immunity through facilitating GSDME-mediated pyroptosis in prostate cancer. Experimental hematology & oncology 37 37528490
2017 Cell Cycle Control by Nuclear Sequestration of CDC20 and CDH1 mRNA in Plant Stem Cells. Molecular cell 36 29225038
2016 Rottlerin inhibits cell growth and invasion via down-regulation of Cdc20 in glioma cells. Oncotarget 36 27626499
2022 The Role of the APC/C and Its Coactivators Cdh1 and Cdc20 in Cancer Development and Therapy. Frontiers in genetics 35 35832196
2017 Cdc20 overexpression is involved in temozolomide-resistant glioma cells with epithelial-mesenchymal transition. Cell cycle (Georgetown, Tex.) 35 29108461
2020 Cdc20 induces the radioresistance of bladder cancer cells by targeting FoxO1 degradation. Cancer letters 33 33290869
2016 Silencing of CDC20 suppresses metastatic castration-resistant prostate cancer growth and enhances chemosensitivity to docetaxel. International journal of oncology 33 27633058
2008 Targeting of CDC20 via small interfering RNA causes enhancement of the cytotoxicity of chemoradiation. Anticancer research 33 18630511
2019 CDC20 contributes to the development of human cutaneous squamous cell carcinoma through the Wnt/β‑catenin signaling pathway. International journal of oncology 32 30816486
2018 Spindle assembly checkpoint MAD2 and CDC20 overexpressions and cell-in-cell formation in gastric cancer and its precursor lesions. Human pathology 31 30448220
2010 Cyclin A and Nek2A: APC/C-Cdc20 substrates invisible to the mitotic spindle checkpoint. Biochemical Society transactions 30 20074038
2023 PRMT6-CDC20 facilitates glioblastoma progression via the degradation of CDKN1B. Oncogene 29 36792756
2021 CDC20 and PTTG1 are Important Biomarkers and Potential Therapeutic Targets for Metastatic Prostate Cancer. Advances in therapy 28 33881746
2022 Impaired Cdc20 signaling promotes senescence in normal cells and apoptosis in non-small cell lung cancer cells. The Journal of biological chemistry 26 35988650
2012 Cell cycle-dependent deposition of CENP-A requires the Dos1/2-Cdc20 complex. Proceedings of the National Academy of Sciences of the United States of America 26 23267073
2018 Cdc20/p55 mediates the resistance to docetaxel in castration-resistant prostate cancer in a Bim-dependent manner. Cancer chemotherapy and pharmacology 25 29605876
2023 CDC20: a novel therapeutic target in cancer. American journal of translational research 24 36915766
2022 Juxtaposition of Bub1 and Cdc20 on phosphorylated Mad1 during catalytic mitotic checkpoint complex assembly. Nature communications 23 36289199
2012 Degradation of human RAP80 is cell cycle regulated by Cdc20 and Cdh1 ubiquitin ligases. Molecular cancer research : MCR 23 22426463
2011 Spindle assembly checkpoint protein Cdc20 transcriptionally activates expression of ubiquitin carrier protein UbcH10. The Journal of biological chemistry 23 21454660
2022 The A20/TNFAIP3-CDC20-CASP1 Axis Promotes Inflammation-mediated Metastatic Disease in Triple-negative Breast Cancer. Anticancer research 22 35093867
2021 CDC20 promotes the progression of hepatocellular carcinoma by regulating epithelial‑mesenchymal transition. Molecular medicine reports 22 33907851
2020 PP1 promotes cyclin B destruction and the metaphase-anaphase transition by dephosphorylating CDC20. Molecular biology of the cell 22 32755477
2017 Different Functionality of Cdc20 Binding Sites within the Mitotic Checkpoint Complex. Current biology : CB 22 28366743
2010 Recruitment of Cdc20 to the kinetochore requires BubR1 but not Mad2 in Drosophila melanogaster. Molecular and cellular biology 22 20421417
2009 Cell-cycle-dependent PC-PLC regulation by APC/C(Cdc20)-mediated ubiquitin-proteasome pathway. Journal of cellular biochemistry 21 19347873
2020 Downregulation of CDC20 suppressed cell proliferation, induced apoptosis, triggered cell cycle arrest in osteosarcoma cells, and enhanced chemosensitivity to cisplatin. Neoplasma 20 33118830
2010 Functional roles of PC-PLC and Cdc20 in the cell cycle, proliferation, and apoptosis. Cell biochemistry and function 20 20517887
2022 Chromobox 4 (CBX4) promotes tumor progression and stemness via activating CDC20 in gastric cancer. Journal of gastrointestinal oncology 19 35837165
2021 CDC20 promotes bone formation via APC/C dependent ubiquitination and degradation of p65. EMBO reports 19 34382737
2020 Downregulation of CDC20 Increases Radiosensitivity through Mcl-1/p-Chk1-Mediated DNA Damage and Apoptosis in Tumor Cells. International journal of molecular sciences 19 32932732
2020 MDM2-P53 Signaling Pathway-Mediated Upregulation of CDC20 Promotes Progression of Human Diffuse Large B-Cell Lymphoma. OncoTargets and therapy 19 33116627
2005 Bub1 and the multilayered inhibition of Cdc20-APC/C in mitosis. Trends in cell biology 19 15866025
2001 Transcriptional upregulation and activation of p55Cdc via p34(cdc2) in Taxol-induced apoptosis. Oncogene 18 11420663
2021 NUSAP1 Accelerates Osteosarcoma Cell Proliferation and Cell Cycle Progression via Upregulating CDC20 and Cyclin A2. OncoTargets and therapy 17 34079289
2019 PP2A-B56 binds to Apc1 and promotes Cdc20 association with the APC/C ubiquitin ligase in mitosis. EMBO reports 17 31825153
2017 R383C mutation of human CDC20 results in idiopathic non-obstructive azoospermia. Oncotarget 17 29245942
2023 The potential role of CDC20 in tumorigenesis, cancer progression and therapy: A narrative review. Medicine 16 37682144
2022 CDC20 is a novel biomarker for improved clinical predictions in epithelial ovarian cancer. American journal of cancer research 16 35968331
2000 High dosage expression of a zinc finger protein, Grt1, suppresses a mutant of fission yeast slp1(+), a homolog of CDC20/p55CDC/Fizzy. Journal of cell science 16 11058086
2020 CDC20 inhibitor Apcin inhibits embryo implantation in vivo and in vitro. Cell biochemistry and function 15 32458533
2017 Fission Yeast Apc15 Stabilizes MCC-Cdc20-APC/C Complexes, Ensuring Efficient Cdc20 Ubiquitination and Checkpoint Arrest. Current biology : CB 15 28366744
2006 A new Mad2-interacting domain of Cdc20 is critical for the function of Mad2-Cdc20 complex in the spindle assembly checkpoint. The Biochemical journal 15 16497171
2023 BUB-1-bound PLK-1 directs CDC-20 kinetochore recruitment to ensure timely embryonic mitoses. Current biology : CB 13 37137308
2006 Effects of histone deacetylase inhibitors on p55CDC/Cdc20 expression in HT29 cell line. Journal of cellular biochemistry 13 16795040
1996 Over-expression of p55Cdc inhibits granulocyte differentiation and accelerates apoptosis in myeloid cells. Oncogene 13 8808696

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