Affinage

Showing FBXO5 — EMI1 is a alias.

FBXO5

F-box only protein 5 · UniProt Q9UKT4

Length
447 aa
Mass
50.1 kDa
Annotated
2026-06-09
59 papers in source corpus 25 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

FBXO5/EMI1 is a cell-cycle regulator that couples DNA replication to mitosis by acting as a potent, multimodal pseudosubstrate inhibitor of the anaphase-promoting complex/cyclosome (APC/C) (PMID:11389834, PMID:16921029). It stably engages APC/C and its co-activators Cdc20 and Cdh1, using a C-terminal D-box to compete with substrates at the D-box receptor while its zinc-binding region (ZBR) and C-terminal tail simultaneously suppress ubiquitin-chain elongation by the E2 enzymes UBCH10/UBE2C and Ube2S (PMID:16921029, PMID:23708605, PMID:23708001); cryo-EM of the APC/C(CDH1):EMI1 ternary complex confirms this multimodal binding mode (PMID:39567505). Through this inhibition EMI1 stabilizes mitotic cyclins and geminin during interphase to promote mitotic entry and prevent re-replication, and its loss triggers premature APC/C activation, geminin/cyclin A destabilization, rereplication, and polyploidy (PMID:17234884, PMID:17485488, PMID:19704007). At the G1/S transition EMI1 switches from an APC/C(CDH1) substrate to its inhibitor, forming a bistable dual-negative feedback loop driven by rising CDK2 activity that enforces irreversible cell-cycle commitment (PMID:29875408). EMI1 levels are tightly controlled by phosphorylation: sequential Plk1 and Cdk1/Cdc2 phosphorylation of a DSGxxS degron generates the recognition site for SCF(β-TrCP/Slimb)-mediated ubiquitylation and destruction, while Evi5 and Pin1 protect the degron during S/G2 (PMID:12791267, PMID:15469984, PMID:16439210, PMID:17159919). Independently of its APC/C-inhibitory role, EMI1's own F-box domain nucleates a canonical SCF ubiquitin ligase that targets substrates for proteasomal degradation, including RAD51—where SCF-EMI1 restrains homologous recombination and modulates PARP-inhibitor and BRCA-deficient repair responses (PMID:30554948, PMID:33785736)—as well as RNF183 in ER-stress apoptosis, DOK6, TP53, and the SARS-CoV-2 protein NSP7 (PMID:38212299, PMID:40577599, PMID:41045986, PMID:41240879). EMI1 also enforces metaphase II/cytostatic-factor arrest and the meiosis I–II transition in oocytes by stabilizing the cyclin B/Cdc20 axis (PMID:11976684, PMID:15701974).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 2001 High

    Established that EMI1 is an APC/C inhibitor controlling mitotic timing, answering how cyclin B is allowed to accumulate before mitosis.

    Evidence Xenopus extract immunodepletion, add-back rescue, Co-IP, and ZBR domain mutagenesis

    PMID:11389834

    Open questions at the time
    • Molecular mechanism of APC/C inhibition (substrate competition vs. catalytic block) not yet resolved
    • Role across full cell cycle in somatic cells untested
  2. 2002 High

    Showed EMI1 is necessary and sufficient to maintain cytostatic-factor metaphase II arrest, defining its role in vertebrate egg cell-cycle arrest.

    Evidence Xenopus egg extract immunodepletion with reciprocal add-back rescue

    PMID:11976684

    Open questions at the time
    • Upstream signals stabilizing EMI1 during CSF arrest unaddressed
    • Relationship to Mos-MAPK pathway not yet defined
  3. 2003 High

    Defined the destruction mechanism: Cdc2 phosphorylation of a DSGxxS degron recruits SCF(β-TrCP) to destroy EMI1 in prophase, explaining how APC/C inhibition is relieved.

    Evidence Phosphorylation and ubiquitination assays, β-TrCP binding, Drosophila slimb mutants

    PMID:12791267

    Open questions at the time
    • Whether Cdc2 is the sole/priming kinase unresolved
    • Spatial regulation of degron phosphorylation unknown
  4. 2004 High

    Identified Plk1 as the strictly required degron kinase and established its co-localization with EMI1 at spindle poles, refining the phosphorylation hierarchy for EMI1 destruction.

    Evidence In vitro kinase and ubiquitination assays, Co-IP, immunofluorescence co-localization, dominant-negative Plk1

    PMID:15469984

    Open questions at the time
    • Order of Plk1 vs. Cdk1 phosphorylation not fully separated
    • In vivo requirement in mammalian cells limited
  5. 2004 Medium

    Linked the Mos-MAPK pathway to EMI1 by showing p90Rsk2 phosphorylates EMI1 to stabilize the EMI1-Cdc20 inhibitory complex during oocyte metaphase arrest.

    Evidence Co-IP, in vitro kinase assay, RNAi, two-cell embryo transfection in mouse oocytes

    PMID:15526037

    Open questions at the time
    • Single-lab finding with two orthogonal methods
    • Phosphosite mapping incomplete
    • Generalizability beyond oocytes untested
  6. 2005 Medium

    Demonstrated EMI1 is required for the meiosis I to meiosis II transition, extending its arrest function to meiotic progression.

    Evidence Neutralizing antibody injection in Xenopus oocytes with cyclin B, Cdc20-depletion, and methyl-ubiquitin rescues

    PMID:15701974

    Open questions at the time
    • Antibody neutralization may have off-target effects
    • Mechanism distinguishing MI vs. MII control unclear
  7. 2006 High

    Defined EMI1 as a pseudosubstrate inhibitor of APC/C(Cdh1), separating D-box-mediated binding affinity from ZBR-mediated catalytic inhibition.

    Evidence In vitro binding and APC ubiquitination assays with D-box and ZBR mutagenesis and substrate competition

    PMID:16921029

    Open questions at the time
    • Structural basis of multimodal binding not yet resolved
    • Contribution of C-terminal tail not yet dissected
  8. 2006 High

    Identified Evi5 as a stabilizer of EMI1 that blocks degron phosphorylation, revealing positive regulation of EMI1 abundance during the cell cycle.

    Evidence Reciprocal Co-IP, in vitro ubiquitination rescue, siRNA with cell-cycle phenotyping

    PMID:16439210

    Open questions at the time
    • Precise cell-cycle window of Evi5 action partially defined
    • Coordination with Pin1 stabilization unresolved
  9. 2006 Medium

    Showed Pin1 stabilizes EMI1 in G2 via isomerization-dependent blocking of β-TrCP binding, adding a phase-specific layer of EMI1 protection.

    Evidence Co-IP in Xenopus XL2 cells, isomerization-dependent β-TrCP competition, loss-of-function cell-cycle analysis

    PMID:17159919

    Open questions at the time
    • Single-lab finding
    • Pin1 target proline residue not definitively mapped
  10. 2007 High

    Established that EMI1 prevents rereplication by stabilizing geminin and cyclin A through APC/C inhibition, defining its genome-protective function.

    Evidence siRNA with non-degradable geminin/cyclin A rescue, flow cytometry, Co-IP

    PMID:17234884

    Open questions at the time
    • Relative contribution of geminin vs. cyclin A context-dependent
    • Mechanism of cyclin A anti-rereplication action partly inferred
  11. 2007 Medium

    Clarified that EMI1 destruction is not required to activate APC/C at mitotic entry, repositioning EMI1's essential role to interphase APC/C inhibition.

    Evidence Live-cell imaging of degradation timing vs. APC/C activation, siRNA, cell-cycle analysis

    PMID:17485488

    Open questions at the time
    • Single method set; contradicts some prior models
    • Does not exclude partial roles for EMI1 turnover at mitosis
  12. 2009 Medium

    Connected EMI1 to the DNA damage response by showing p21-mediated EMI1 downregulation activates APC/C to enforce G2 arrest.

    Evidence siRNA, p21+/+ vs p21-/- epistasis, flow cytometry, cyclin Western blots

    PMID:19211842

    Open questions at the time
    • Mechanism of p21-driven EMI1 loss not defined
    • Single-lab finding
  13. 2009 Medium

    Showed EMI1 depletion causes rereplication and polyploidy in human cells and zebrafish and creates dependence on topoisomerase IIα decatenation, demonstrating in vivo genome-stability roles.

    Evidence Zebrafish morpholino and human siRNA knockdown, flow cytometry, metaphase chromosome preparation, topoisomerase inhibition

    PMID:19704007

    Open questions at the time
    • Single-lab finding
    • Molecular basis of topoisomerase dependence not fully resolved
  14. 2011 Medium

    Linked oncogenic signaling to EMI1 stability by showing Bcr-Abl/Src tyrosine phosphorylation at Tyr142 stabilizes EMI1 and sustains Skp2 in CML cells.

    Evidence Kinase inhibitors, Y142F mutagenesis, in vitro Src phosphorylation, Co-IP, ubiquitination and half-life assays

    PMID:20717963

    Open questions at the time
    • Single-lab finding
    • In vivo relevance of Tyr142 in normal cells untested
  15. 2013 High

    Resolved the structural and kinetic basis of multimodal APC/C inhibition, showing the C-terminal domain blocks substrate binding while ZBR and tail suppress chain elongation by distinct E2s.

    Evidence NMR, cryo-EM, APC/C ubiquitination kinetics, domain mutagenesis (two complementary studies)

    PMID:23708001 PMID:23708605

    Open questions at the time
    • Atomic-resolution view of the full ternary complex not yet achieved
    • Regulation of these motifs by phosphorylation unaddressed
  16. 2018 High

    Defined the EMI1–APC/C(CDH1) dual-negative feedback switch as the bistable basis of irreversible G1/S commitment, integrating EMI1 regulation into cell-cycle decision-making.

    Evidence Live-cell reporters, in vitro reconstitution of the switch, mathematical modeling, siRNA

    PMID:29875408

    Open questions at the time
    • Quantitative thresholds in vivo across cell types not mapped
    • Coupling to mitogen signaling partly inferred
  17. 2018 High

    Established a distinct SCF-EMI1 ligase function: the F-box domain assembles an SCF that degrades RAD51 to restrain homologous recombination, with implications for PARP-inhibitor sensitivity in BRCA-deficient cells.

    Evidence PARPi-sensitivity genetic screen, ΔF-box mutagenesis, Co-IP, ubiquitination assays, siRNA, orthotopic mouse model

    PMID:30554948

    Open questions at the time
    • Whether SCF-EMI1 and APC/C-inhibitory functions are temporally separated unclear
    • Full substrate repertoire of SCF-EMI1 unknown
  18. 2021 Medium

    Showed PUMA scaffolds cytoplasmic EMI1-mediated RAD51 ubiquitination to block RAD51 nuclear import and HR in progenitor cells, adding a subcellular dimension to EMI1's repair regulation.

    Evidence Co-IP, ubiquitination assays, subcellular fractionation, nuclear translocation and HR repair assays

    PMID:33785736

    Open questions at the time
    • Single-lab finding
    • Direct vs. scaffolded EMI1-RAD51 contact not separated from PUMA role
  19. 2022 Medium

    Mapped context-dependent activities of individual EMI1 C-terminal motifs, finding inhibition of substrate recruitment and E2 activity but paradoxical activation of UBE2C priming by an isolated peptide.

    Evidence In vitro ubiquitination assays with EMI1 truncations and point mutants, APC/C reconstitution

    PMID:35634770

    Open questions at the time
    • Physiological relevance of the activating peptide fragment unknown
    • Single comprehensive in vitro study
  20. 2024 High

    Provided a 2.9 Å cryo-EM structure of the APC/C(CDH1):EMI1 ternary complex, confirming multimodal EMI1 binding and resolving regulatory disordered regions and an APC2 zinc module.

    Evidence Cryo-EM with AlphaFold-assisted modeling and experimental zinc detection

    PMID:39567505

    Open questions at the time
    • Dynamics of the inhibitory-to-substrate transition not captured
    • Structures with phosphorylated EMI1 absent
  21. 2024 Medium

    Extended SCF-EMI1 substrate repertoire to RNF183, linking the FBXO5/RNF183 axis to control of ER stress-induced apoptosis.

    Evidence Co-IP, ubiquitination assays, ΔF-box mutagenesis, siRNA, tumor xenograft

    PMID:38212299

    Open questions at the time
    • Single-lab finding
    • How ER stress regulates this axis undefined
  22. 2025 Medium

    Identified additional SCF-EMI1 substrates DOK6 and TP53 and an antiviral role degrading SARS-CoV-2 NSP7, broadening FBXO5 ligase function into glioma drug resistance, stem-cell differentiation, and infection.

    Evidence CRISPR/esiRNA screens, Co-IP, K48-linkage ubiquitination assays, CHX chase, in vivo tumor models, SARS-CoV-2 infection assays

    PMID:40577599 PMID:41045986 PMID:41240879

    Open questions at the time
    • Each substrate reported by a single lab
    • Degron/recognition motifs for these substrates not defined
    • Relationship to cell-cycle SCF-EMI1 function unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How EMI1's APC/C-inhibitory and SCF-ligase functions are temporally, spatially, and structurally partitioned within a single protein remains unresolved.
  • No structural model of the F-box/SCF-EMI1 complex with substrates
  • Degron recognition logic for the expanding SCF-EMI1 substrate set undefined
  • Switch governing inhibitor vs. ligase mode unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0098772 molecular function regulator activity 4 GO:0016874 ligase activity 3 GO:0140313 molecular sequestering activity 2
Localization
GO:0005634 nucleus 1 GO:0005815 microtubule organizing center 1 GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-1474165 Reproduction 2 R-HSA-69306 DNA Replication 2 R-HSA-73894 DNA Repair 2 R-HSA-5357801 Programmed Cell Death 1
Partners
BTRC (Β-TRCP)CDC20CDH1/FZR1EVI5PIN1PLK1RAD51TP53
Complex memberships
APC/C (as bound inhibitor)SCF (Skp1-Cul1-F-box)

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 EMI1 (FBXO5) binds the APC activator Cdc20 and inhibits APC/C ubiquitin ligase activity; it contains a zinc-binding region (ZBR) essential for APC inhibition; immunodepletion from cycling Xenopus extracts delays cyclin B accumulation and mitotic entry, while non-destructible EMI1 stabilizes APC substrates and causes mitotic block. Xenopus extract immunodepletion, gain-of-function rescue, Co-immunoprecipitation, domain mutagenesis (ZBR) Cell High 11389834
2002 EMI1 is necessary and sufficient to inhibit APC/C(Cdc20) and maintain CSF (cytostatic factor) metaphase II arrest in Xenopus eggs; immunodepletion of EMI1 from CSF extracts causes premature cyclin B degradation and mitotic exit in the absence of calcium. Xenopus egg extract immunodepletion, add-back rescue experiments Nature High 11976684
2003 EMI1 is phosphorylated by Cdc2 on a DSGxxS consensus degron, which is then recognized by the SCF(β-TrCP/Slimb) ubiquitin ligase, leading to EMI1 ubiquitylation and destruction in prophase; failure of β-TrCP-dependent EMI1 destruction stabilizes APC substrates and causes mitotic catastrophe including centrosome overduplication. Phosphorylation assays, SCF(β-TrCP) binding assays, loss-of-function in cells and Drosophila slimb mutants, ubiquitination assays Developmental cell High 12791267
2004 Polo-like kinase 1 (Plk1) is strictly required for EMI1 destruction: Plk1 phosphorylates EMI1 to generate the DSGxxS degron recognized by SCF(β-TrCP), stimulating β-TrCP binding and ubiquitination in vitro; cyclin B/Cdk1 enhances these effects. Plk1 binds EMI1 in mitosis and both proteins co-localize on mitotic spindle poles. In vitro kinase assays, ubiquitination assays, Co-immunoprecipitation, co-localization by immunofluorescence, Plk1 overexpression and dominant-negative approaches Molecular biology of the cell High 15469984
2006 EMI1 acts as a pseudosubstrate inhibitor of APC/C(Cdh1): it stably binds both APC/C and its Cdh1 activator, competes with APC substrates at the D-box receptor site via its C-terminal D-box (providing binding affinity), and antagonizes E3 ligase activity via its ZBR independent of tight APC binding. Mutation of the ZBR converts EMI1 into a D-box-dependent APC substrate. In vitro binding assays, APC ubiquitination assays, mutagenesis of D-box and ZBR, competition assays with APC substrates Genes & development High 16921029
2006 The Evi5 oncogene binds EMI1 adjacent to its DSGxxS degron and stabilizes EMI1 by blocking degron phosphorylation by Polo-like kinases and subsequent β-TrCP binding, thereby antagonizing SCF(β-TrCP)-dependent EMI1 ubiquitination; Evi5 depletion causes precocious EMI1 degradation, premature APC/C activation, cyclin destruction, and mitotic catastrophe. Co-immunoprecipitation (Evi5-EMI1 interaction), in vitro ubiquitination assays, siRNA knockdown with cell cycle phenotyping Cell High 16439210
2006 Pin1 stabilizes EMI1 during G2 phase by binding EMI1 and preventing its association with SCF(β-TrCP) in an isomerization-dependent manner; Pin1-EMI1 interaction is detectable in vivo during G2, protecting EMI1 from degradation at this cell cycle phase. Co-immunoprecipitation in Xenopus XL2 cells, Pin1-EMI1 binding assays, isomerization-dependent competition with β-TrCP, loss-of-function cell cycle analysis EMBO reports Medium 17159919
2007 EMI1 is essential for preventing rereplication: EMI1 depletion causes premature APC/C activation, destabilizing geminin and cyclin A (which redundantly prevent rereplication in mammalian cells); cyclin A's anti-rereplication role is mediated through its association with Cdk2 and Cdk1. siRNA knockdown, rescue experiments with non-degradable geminin/cyclin A, flow cytometry (rereplication readout), co-immunoprecipitation Genes & development High 17234884
2007 EMI1 degradation is NOT required to activate APC/C at mitotic entry; instead, EMI1's essential function is to inhibit APC/C in interphase to stabilize mitotic cyclins and geminin to promote mitotic entry and prevent rereplication. Live-cell imaging of EMI1 degradation timing vs. APC/C activation, siRNA knockdown, cell cycle analysis The Journal of cell biology Medium 17485488
2013 EMI1's 143-residue C-terminal domain inhibits APC/C(CDH1) through multiple mechanisms simultaneously: the intrinsically disordered D-box, linker, and tail elements together with the structured ZBR bind distinct regions of APC/C(CDH1) to synergistically block the substrate-binding site and inhibit ubiquitin-chain elongation. NMR, cryo-electron microscopy, enzymology (APC/C ubiquitination assays), domain deletion/mutation analysis Nature structural & molecular biology High 23708605
2013 EMI1 inhibits APC ubiquitylation at two distinct steps: (1) substrate binding and (2) ubiquitin chain elongation; the ZBR allows multiple monoubiquitylation of substrates but preferentially suppresses ubiquitin chain elongation by UBCH10; the C-terminal tail of EMI1 antagonizes chain elongation by Ube2S through competitive inhibition of its binding to the APC cullin subunit via electrostatic interaction. In vitro APC ubiquitination kinetic assays, domain mutagenesis, competition binding assays with Ube2S Nature cell biology High 23708001
2018 Cell-cycle commitment at the G1/S transition is mediated by an EMI1-APC/C(CDH1) dual-negative feedback switch: EMI1 transitions from being a substrate of APC/C(CDH1) to being its inhibitor, triggered by increased CDK2 activity and EMI1 mRNA expression. In vitro reconstitution showed this dual-negative feedback is bistable and irreversible. Human cell models with live-cell reporters, in vitro reconstitution of EMI1-APC/C switch, mathematical modeling, siRNA knockdown, cell synchronization Nature High 29875408
2018 EMI1's F-box domain is required for assembly of a canonical SCF ubiquitin ligase complex that constitutively targets RAD51 for proteasomal degradation; in response to genotoxic stress, CHK1-mediated phosphorylation of RAD51 counteracts EMI1-dependent degradation by enhancing RAD51's affinity for BRCA2. EMI1 depletion restores RAD51 accumulation and homologous recombination repair in BRCA1-deficient cells. Genetic screen for PARPi sensitivity, F-box domain mutagenesis, Co-immunoprecipitation (EMI1-RAD51 SCF complex), ubiquitination assays, siRNA knockdown, orthotopic mouse model Molecular cell High 30554948
2004 p90Rsk2 associates with and phosphorylates EMI1 upstream of the Cdc20 binding region, stabilizing the EMI1-Cdc20 interaction and contributing to metaphase arrest in mouse oocytes; the Mos-MAPK pathway establishes CSF activity through stabilization of an APC-inhibitory complex composed of EMI1 and Cdc20. Co-immunoprecipitation (p90Rsk2-EMI1), in vitro phosphorylation assays, RNA interference, transfection into two-cell embryos The EMBO journal Medium 15526037
2011 Bcr-Abl increases EMI1 stability through Src kinase-mediated tyrosine phosphorylation of EMI1 at Tyr142; mutation Y142F abolishes phosphorylation by recombinant Src kinase and reduces EMI1 stability. Stable EMI1 prevents APC/Cdh1-mediated ubiquitination of Skp2, thereby maintaining Skp2 protein levels in CML cells. Kinase inhibitor treatment, site-directed mutagenesis (Y142F), in vitro phosphorylation by recombinant Src, Co-immunoprecipitation, ubiquitination assays, half-life analysis Journal of cellular physiology Medium 20717963
2024 FBXO5 directly binds RNF183 and promotes its ubiquitin-dependent proteasomal degradation through its F-box domain; this FBXO5/RNF183 axis regulates ER stress-induced apoptosis. F-box domain deletion (ΔF-box mutant) abolishes the anti-apoptotic effect, establishing requirement for SCF complex assembly. Co-immunoprecipitation (FBXO5-RNF183), ubiquitination assays, F-box deletion mutagenesis, siRNA knockdown, in vivo tumor xenograft Cell death & disease Medium 38212299
2021 PUMA associates with EMI1 and RAD51 in the cytoplasm, facilitating EMI1-mediated cytoplasmic RAD51 ubiquitination and degradation, thereby inhibiting RAD51 nuclear translocation and homologous recombination DNA repair in embryonic and hematopoietic progenitor cells. Co-immunoprecipitation (PUMA-EMI1-RAD51), ubiquitination assays, subcellular fractionation, nuclear translocation assays, HR repair assays Signal transduction and targeted therapy Medium 33785736
2009 EMI1 down-regulation by p21(WAF1) after DNA damage contributes to APC/C activation, resulting in degradation of cyclins A2 and B1 and maintenance of G2 arrest; siRNA-mediated EMI1 depletion prevents irradiated p21-deficient cells from entering mitosis, and this effect is counteracted by APC/C inactivation. siRNA knockdown, genetic epistasis (p21+/+ vs p21-/- cells), flow cytometry (G2 arrest), Western blot for cyclin levels Molecular biology of the cell Medium 19211842
2024 Cryo-EM structures of human APC/C(CDH1):EMI1 ternary complex at 2.9 Å resolution reveal the N-terminus of CDH1 (CDH1α1) at the APC/C interface; a zinc-binding module in APC2 confers structural stability; intrinsically disordered regions of multiple APC/C subunits involved in assembly and regulation are resolved, confirming multimodal EMI1 binding. Cryo-electron microscopy, AlphaFold-assisted model building, experimental zinc ion detection Nature communications High 39567505
2022 Using comprehensive enzyme assays, the context-dependent roles of multiple EMI1 C-terminal motifs were determined: EMI1 motifs inhibit both APC/C substrate recruitment and APC/C-associated E2s (UBE2C and UBE2S); additionally, an isolated C-terminal peptide fragment of EMI1 activates APC/C-dependent substrate priming by UBE2C. In vitro ubiquitination assays with truncation and point mutants of EMI1, APC/C reconstitution Protein science Medium 35634770
2025 FBXO5 mediates K48-linked ubiquitination and proteasomal degradation of SARS-CoV-2 NSP7; NSP7 ubiquitination is co-regulated by β-TrCP1 and the kinase TAF1. A small molecule that disrupts the β-TrCP1-FBXO5 interaction stabilizes FBXO5 and enhances NSP7 degradation. esiRNA screen, ubiquitination assays (K48-linkage specific), Co-immunoprecipitation (β-TrCP1-FBXO5), small molecule stabilizer screen, SARS-CoV-2 infection assays Advanced science Medium 40577599
2025 FBXO5 promotes K48-linked polyubiquitination and proteasomal degradation of DOK6; DOK6 depletion enhances mechanical rigidity in GBM tumor cells and initiates survival signaling that confers temozolomide resistance. CRISPR/Cas9 sgRNA library screen, Co-immunoprecipitation, ubiquitination assays (K48 linkage), FBXO5 knockdown/overexpression, in vitro and in vivo tumor models Cancer letters Medium 41045986
2025 FBXO5 facilitates TP53 ubiquitination-mediated degradation; Co-IP confirmed direct interaction between FBXO5 and TP53; CHX chase and ubiquitination assays established that FBXO5 reduces TP53 protein stability via the proteasome pathway, promoting osteogenic differentiation of human stem cells from the apical papilla. Co-immunoprecipitation, cycloheximide chase assay, ubiquitination assay, siRNA knockdown, osteogenic differentiation assays International dental journal Medium 41240879
2005 EMI1 is required for the meiosis I to meiosis II (MI-MII) transition in Xenopus oocytes: acute antibody-mediated neutralization of EMI1 immediately after GVBD causes rapid loss of Cdc2 activity with simultaneous cyclin B loss and MAPK inactivation, causing chromosome decondensation and DNA replication instead of MII progression; these defects are rescued by non-destructible cyclin B, Cdc20 depletion, or methyl-ubiquitin. Neutralizing antibody injection in Xenopus oocytes, rescue with Delta90 cyclin B, Cdc20 depletion, methyl-ubiquitin, cell cycle phase analysis Cell cycle Medium 15701974
2009 EMI1 depletion in human cells or zebrafish embryos causes chromosomal rereplication, leading to rereplicated unsegregated chromosomes and polyploidy; EMI1-depleted mammalian cells rely on topoisomerase IIα-dependent mitotic decatenation to progress through metaphase. Morpholino knockdown in zebrafish, siRNA in human cells, flow cytometry, metaphase chromosome preparation, BrdU incorporation, topoisomerase IIα inhibition Molecular and cellular biology Medium 19704007

Source papers

Stage 0 corpus · 59 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex. Cell 323 11389834
2003 Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase. Developmental cell 302 12791267
2004 Plk1 regulates activation of the anaphase promoting complex by phosphorylating and triggering SCFbetaTrCP-dependent destruction of the APC Inhibitor Emi1. Molecular biology of the cell 180 15469984
2006 Emi1 stably binds and inhibits the anaphase-promoting complex/cyclosome as a pseudosubstrate inhibitor. Genes & development 170 16921029
2007 The APC/C inhibitor, Emi1, is essential for prevention of rereplication. Genes & development 166 17234884
2018 EMI1 switches from being a substrate to an inhibitor of APC/CCDH1 to start the cell cycle. Nature 111 29875408
2007 Emi1 is needed to couple DNA replication with mitosis but does not regulate activation of the mitotic APC/C. The Journal of cell biology 109 17485488
2002 Emi1 is required for cytostatic factor arrest in vertebrate eggs. Nature 104 11976684
2006 The evi5 oncogene regulates cyclin accumulation by stabilizing the anaphase-promoting complex inhibitor emi1. Cell 83 16439210
2013 Electron microscopy structure of human APC/C(CDH1)-EMI1 reveals multimodal mechanism of E3 ligase shutdown. Nature structural & molecular biology 79 23708605
2018 The F-Box Domain-Dependent Activity of EMI1 Regulates PARPi Sensitivity in Triple-Negative Breast Cancers. Molecular cell 67 30554948
2013 Emi1 preferentially inhibits ubiquitin chain elongation by the anaphase-promoting complex. Nature cell biology 58 23708001
2009 Cyclin A2-cyclin-dependent kinase 2 cooperates with the PLK1-SCFbeta-TrCP1-EMI1-anaphase-promoting complex/cyclosome axis to promote genome reduplication in the absence of mitosis. Molecular and cellular biology 56 19822658
2009 DNA damage triggers p21WAF1-dependent Emi1 down-regulation that maintains G2 arrest. Molecular biology of the cell 52 19211842
2016 In vivo overexpression of Emi1 promotes chromosome instability and tumorigenesis. Oncogene 51 27065322
2006 Pin1 stabilizes Emi1 during G2 phase by preventing its association with SCF(betatrcp). EMBO reports 45 17159919
2004 Emi1-mediated M-phase arrest in Xenopus eggs is distinct from cytostatic factor arrest. Proceedings of the National Academy of Sciences of the United States of America 43 15314241
2006 Mouse emi1 has an essential function in mitotic progression during early embryogenesis. Molecular and cellular biology 42 16809773
2006 Overexpression of the anaphase promoting complex/cyclosome inhibitor Emi1 leads to tetraploidy and genomic instability of p53-deficient cells. Cell cycle (Georgetown, Tex.) 41 16861914
2008 Emi1 protein accumulation implicates misregulation of the anaphase promoting complex/cyclosome pathway in ovarian clear cell carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 37 18204430
2007 Loss of Emi1-dependent anaphase-promoting complex/cyclosome inhibition deregulates E2F target expression and elicits DNA damage-induced senescence. Molecular and cellular biology 34 17875940
2009 Emi1 maintains genomic integrity during zebrafish embryogenesis and cooperates with p53 in tumor suppression. Molecular and cellular biology 32 19704007
2004 Functional interaction between p90Rsk2 and Emi1 contributes to the metaphase arrest of mouse oocytes. The EMBO journal 32 15526037
2020 An upstream open reading frame regulates vasculogenic mimicry of glioma via ZNRD1-AS1/miR-499a-5p/ELF1/EMI1 pathway. Journal of cellular and molecular medicine 22 32368853
2011 Bcr-Abl-induced tyrosine phosphorylation of Emi1 to stabilize Skp2 protein via inhibition of ubiquitination in chronic myeloid leukemia cells. Journal of cellular physiology 22 20717963
2008 Defining the role of Emi1 in the DNA replication-segregation cycle. Chromosoma 22 18317792
2010 Characterization of harpy/Rca1/emi1 mutants: patterning in the absence of cell division. Developmental dynamics : an official publication of the American Association of Anatomists 21 20146251
2005 Emi1 class of proteins regulate entry into meiosis and the meiosis I to meiosis II transition in Xenopus oocytes. Cell cycle (Georgetown, Tex.) 21 15701974
2024 FBXO5-mediated RNF183 degradation prevents endoplasmic reticulum stress-induced apoptosis and promotes colon cancer progression. Cell death & disease 19 38212299
2013 Selective enhancing effect of early mitotic inhibitor 1 (Emi1) depletion on the sensitivity of doxorubicin or X-ray treatment in human cancer cells. The Journal of biological chemistry 17 23645673
2021 Modulation of Early Mitotic Inhibitor 1 (EMI1) depletion on the sensitivity of PARP inhibitors in BRCA1 mutated triple-negative breast cancer cells. PloS one 16 33412559
2021 PUMA facilitates EMI1-promoted cytoplasmic Rad51 ubiquitination and inhibits DNA repair in stem and progenitor cells. Signal transduction and targeted therapy 16 33785736
2003 Emi1 proteolysis: how SCF(beta-Trcp1) helps to activate the anaphase-promoting complex. Molecular cell 16 12820955
2011 Chromium induces chromosomal instability, which is partly due to deregulation of BubR1 and Emi1, two APC/C inhibitors. Cell cycle (Georgetown, Tex.) 14 21670593
2024 METTL16 regulates the mRNA stability of FBXO5 via m6A modification to facilitate the malignant behavior of breast cancer. Cancer & metabolism 13 39061113
2018 Two Transcripts of FBXO5 Promote Migration and Osteogenic Differentiation of Human Periodontal Ligament Mesenchymal Stem Cells. BioMed research international 13 29850565
2013 Human papillomavirus type 16 E7 oncoprotein inhibits the anaphase promoting complex/cyclosome activity by dysregulating EMI1 expression in mitosis. Virology 13 24074588
2022 The role of Fbxo5 in the development of human malignant tumors. American journal of cancer research 11 35530293
2012 Rereplication in emi1-deficient zebrafish embryos occurs through a Cdh1-mediated pathway. PloS one 11 23082190
2022 Examining the mechanistic relationship of APC/CCDH1 and its interphase inhibitor EMI1. Protein science : a publication of the Protein Society 9 35634770
2024 Downregulation of Splicing Factor PTBP1 Curtails FBXO5 Expression to Promote Cellular Senescence in Lung Adenocarcinoma. Current issues in molecular biology 8 39057099
2024 Cryo-EM structures of apo-APC/C and APC/CCDH1:EMI1 complexes provide insights into APC/C regulation. Nature communications 8 39567505
2023 Licochalcone A induces cell cycle arrest and apoptosis via suppressing MAPK signaling pathway and the expression of FBXO5 in lung squamous cell cancer. Oncology reports 8 37859622
2014 Thymosin beta-4 knockdown in IEC-6 normal intestinal epithelial cells induces DNA re-replication via downregulating Emi1. Journal of cellular physiology 8 24615569
2013 EMI1, a three-in-one ubiquitylation inhibitor. Nature structural & molecular biology 8 23984442
2023 Exploring the role of FBXO5 in gastric cancer. Molecular and cellular probes 7 37121410
2023 Afu-Emi1 Contributes to Stress Adaptation and Voriconazole Susceptibility in Aspergillus fumigatus. Microbiology spectrum 6 37039674
2024 Loss of EMI1 compromises chromosome stability and is associated with cellular transformation in colonic epithelial cell contexts. British journal of cancer 2 39358461
2023 Expression significance of Emi1, UBCH10 and CyclinB1 in esophageal squamous cell carcinoma. Pathology oncology research : POR 2 37168048
2023 Effect of Emi1 gene silencing on the proliferation and invasion of human breast cancer cells. BMC molecular and cell biology 2 38041032
2014 [Expression and clinicopathological significance of Emi1 in breast carcinoma]. Zhonghua yi xue za zhi 2 25312659
2025 NSP7 Molecular Degrader Attenuates Coronaviral Infection Through the β-TrCP1/FBXO5 Axis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 40577599
2025 Integrative analysis identifies FBXO5 as a critical mediator of CRPC progression and bone metastatic potential. Discover oncology 1 40775408
2026 Thalidomide Synergistically Regulates Cell Cycle and Endoplasmic Reticulum Stress to Alleviate RPE Oxidative Damage Through the E2F2-FBXO5 Pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 41467813
2025 Targeting the FBXO5-DOK6 axis to overcome temozolomide resistance in glioblastoma via proteasome-cytomechanics regulation. Cancer letters 0 41045986
2025 FBXO5 drives hepatocellular carcinoma progression and is a target for tea polyphenol-mediated inhibition. Translational cancer research 0 41234846
2025 FBXO5 alleviates apical periodontitis by facilitating TP53 protein degradation. International dental journal 0 41240879
2025 CircUSP36 promotes FBXO5 expression to accelerate cervical cancer progression by targeting miR-520d-5p. Cytotechnology 0 41250776
2024 Role of arbutin in the inhibition of FBXO5 in hepatocellular carcinoma. Discover oncology 0 39714552

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