Affinage

APC2

Apolipoprotein C-II · UniProt P02655

Length
101 aa
Mass
11.3 kDa
Annotated
2026-06-09
52 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

APC2 is a multifunctional scaffold that operates in two largely separable domains of cell biology: as the cullin subunit of the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase, and as a negative regulator of Wnt/Wingless signaling (PMID:9430641, PMID:9823329). Within the APC/C, APC2 dimerizes with the RING subunit APC11 to form the minimal catalytic ubiquitin-ligase module that, with E2 enzymes (Ubc4/UbcH10), ubiquitinates mitotic substrates such as securin and cyclin B1 (PMID:11739784, PMID:22417125); cryo-EM maps APC2 and the Cdh1 coactivator to the substrate-ubiquitination face of the asymmetric complex, where coactivator binding repositions the catalytic module to license E2 engagement [PMID:16364912, PMID:bio_10.1101_2024.06.19.599685]. Loss of APC/C function via APC2 produces metaphase arrest and failed degradation of mitotic regulators, and reduced APC2 contributes to chromosome segregation and sister-chromatid cohesion defects (PMID:9430641, PMID:25257309). Independently of mitosis, APC2 restrains Wnt signaling: its 20-amino-acid APC-repeat motifs bind β-catenin/Armadillo and its SAMP domains bind Axin/conductin, assembling a destruction complex that depletes β-catenin and downregulates β-catenin–TCF transcription (PMID:9823329, PMID:10021369), and it recruits Tankyrase into this complex through a conserved C-terminal motif (PMID:27068743). APC2 also stabilizes and regulates microtubules: it promotes plus-end dynamics of minus-end-out microtubules in dendrites and stabilizes microtubules in growth cones to direct axon guidance and dendritic morphology (PMID:30018294, PMID:19759310), and it associates with cortical actin through self-association and coiled-coil domains to tether mitotic spindles and organize the actin cortex (PMID:11584277, PMID:30019417, PMID:21486956). APC2 is a downstream effector of NSD1 in neuronal migration, and its loss causes Sotos-syndrome-like learning and morphological defects in mice (PMID:25753423).

Mechanistic history

Synthesis pass · year-by-year structured walk · 27 steps
  1. 1998 High

    Established that APC2 is a functional subunit of the anaphase-promoting complex, answering whether the cullin-like protein has a direct cell-cycle role.

    Evidence Temperature-sensitive yeast rsi1/apc2 mutants, PDS1-deletion epistasis, co-IP with Cdc23p

    PMID:9430641

    Open questions at the time
    • Did not define the catalytic mechanism or direct E2 partner of APC2 within the complex
  2. 1998 Medium

    Defined APC2 as a Wnt-pathway negative regulator by showing its 20-aa repeats bind and deplete β-catenin and modulate β-catenin–TCF transcription.

    Evidence Domain binding assay plus TOP-flash reporter in APC-null colon carcinoma cells

    PMID:9823329

    Open questions at the time
    • Single lab; did not establish the Axin-binding requirement or in vivo significance
  3. 1999 Medium

    Connected APC2 to the destruction-complex scaffold by mapping the two SAMP domains required for Axin/conductin binding.

    Evidence Domain-deletion binding and transient TOP/FOP transcriptional assays in APC-null cells

    PMID:10021369

    Open questions at the time
    • Did not show stoichiometry or assembly of the full destruction complex
  4. 1999 High

    Validated APC2 as a genetically defined Wnt antagonist in vivo and hinted at a cytoskeletal association, broadening its role beyond a biochemical interactor.

    Evidence Drosophila genetic epistasis, direct Armadillo binding, immunolocalization with actin

    PMID:10491393

    Open questions at the time
    • Cytoskeletal association was correlative; functional consequence not yet tested
  5. 2001 High

    Defined the minimal catalytic module of the APC/C, showing the APC2–APC11 heterodimer with an E2 suffices for substrate ubiquitination but lacks specificity.

    Evidence Baculoviral in vitro reconstitution, binding-domain mapping, APC11 Zn-residue mutagenesis

    PMID:11739784

    Open questions at the time
    • Substrate specificity determinants reside elsewhere; structural basis of E2 positioning unresolved
  6. 2001 High

    Revealed a non-degradative, cytoskeletal function: APC2–Armadillo complexes tether mitotic spindles to cortical actin under GSK-3/Zw3 control.

    Evidence Drosophila immunolocalization, live imaging, zw3 loss-of-function epistasis

    PMID:11584277

    Open questions at the time
    • Molecular link between APC2 and the actin cortex not yet defined at the domain level
  7. 2002 High

    Demonstrated global functional redundancy between APC2 and APC1 in restricting β-catenin–driven transcription throughout development.

    Evidence Drosophila double-mutant epistasis, nuclear Armadillo staining, reporter assays

    PMID:11923210 PMID:12297097 PMID:12297098

    Open questions at the time
    • Did not explain why two paralogs with distinct localizations are both required
  8. 2002 Medium

    Separated a Wnt-independent APC2 role, showing neuroblast maintenance defects in APC2/APC1 double mutants without Wg misregulation.

    Evidence Drosophila genetic double-mutant analysis with Wg-pathway epistasis ruled out

    PMID:12297097

    Open questions at the time
    • The implicated cytoskeletal/adhesive mechanism was inferred, not directly demonstrated
  9. 2000 Medium

    Identified APC2 as a regulator of partner subcellular localization, redirecting 53BP2 to the perinuclear region via its C-terminus.

    Evidence Yeast two-hybrid, in vitro binding, domain mapping, confocal co-localization

    PMID:10646860

    Open questions at the time
    • Functional consequence of 53BP2 relocalization unknown; single lab
  10. 2001 Medium

    Characterized endogenous APC2 localization to Golgi and actin filaments, with actin association resistant to cytochalasin D.

    Evidence Immunofluorescence, cytochalasin D perturbation, FISH allelic imbalance

    PMID:11691822

    Open questions at the time
    • Overexpression artifacts possible; direct versus indirect actin binding not resolved
  11. 2002 Medium

    Extended APC/C substrate recognition by showing inversin binds APC2 through D-box motifs, marking it as a candidate degradation target.

    Evidence Co-IP and site-directed D-box mutagenesis

    PMID:12471060

    Open questions at the time
    • Did not demonstrate APC/C-dependent inversin turnover directly
  12. 2005 High

    Placed APC2 structurally on the ubiquitination face of the APC/C and showed Cdh1 activates by conformational rearrangement, not only substrate recruitment.

    Evidence Cryo-EM 3D reconstruction with STEM mass measurement and antibody subunit labeling

    PMID:16364912

    Open questions at the time
    • Low-resolution; atomic basis of the conformational change not resolved
  13. 2009 High

    Established APC2 as a microtubule stabilizer required for axon guidance, defining a discrete cytoskeletal function in neurons.

    Evidence Overexpression/shRNA in chick retina, in vitro guidance assay, in vivo retinotectal mapping

    PMID:19759310

    Open questions at the time
    • Direct microtubule-binding mode not mapped at the domain level here
  14. 2010 Medium

    Revealed regulation of free APC2 levels and the cell cycle by the F-box protein FBG1, which binds APC2 via a D-box and sequesters it.

    Evidence Co-IP, D-box mutagenesis, FACS cell-cycle analysis

    PMID:21135578

    Open questions at the time
    • Whether sequestration acts on the APC/C or Wnt pool of APC2 unclear
  15. 2011 High

    Dissected APC2 cortical targeting, showing Armadillo repeats plus a novel C-terminal domain drive localization and self-association, separable from Wnt function.

    Evidence Domain-deletion in S2 cells, rescue of actin and Wnt phenotypes, co-IP for self-association

    PMID:21486956

    Open questions at the time
    • The cortical receptor/anchor that recruits APC2 not identified
  16. 2012 Medium

    Showed the APC2–APC11 module recruits the E2-C enzyme Vihar, confirming the E2-loading role of the catalytic module in vivo.

    Evidence Drosophila genetic complementation, IP/pull-down, yeast complementation

    PMID:22417125

    Open questions at the time
    • Did not resolve conformational requirements for E2 engagement
  17. 2013 High

    Linked APC2 cortical/cytoskeletal function to genome stability via a centrosome-separation→ectopic-furrow cascade promoting mitotic fidelity.

    Evidence Drosophila loss-of-function, live imaging of segregation errors, Axin epistasis

    PMID:24026117

    Open questions at the time
    • Mechanistic link between cortical APC2 and centrosome separation not molecularly defined
  18. 2014 High

    Connected APC2 levels to cohesion by showing SNW1-dependent APC2 splicing maintains APC/C activity and prevents cohesion fatigue.

    Evidence siRNA, transcriptome splicing analysis, intron-less cDNA rescue, cohesion assays

    PMID:25257309

    Open questions at the time
    • A regulatory rather than direct APC2 mechanism; APC2-specific splicing dependence not generalized
  19. 2015 High

    Defined APC2 as a downstream effector of NSD1 in neuronal migration and tied its loss to Sotos-syndrome-like neurological phenotypes.

    Evidence Apc2-/- mice, patient exome, Nsd1 knockdown with forced Apc2 rescue, behavioral assays

    PMID:25753423

    Open questions at the time
    • The cytoskeletal step downstream of NSD1→APC2 not fully resolved
  20. 2016 High

    Identified Tankyrase as a destruction-complex component recruited by an APC2 C-terminal motif and a PARylation target distinct from Axin in its regulation.

    Evidence Y2H, co-IP, in vitro PARylation, motif mapping, Wnt reporter with TNKS inhibitors

    PMID:27068743

    Open questions at the time
    • Functional consequence of APC2 PARylation (vs Axin) not defined since it does not control APC2 levels
  21. 2018 High

    Established APC2 control of minus-end-out microtubule dynamics in dendrites, mapping its localization to LC8-binding and microtubule-interacting domains.

    Evidence shRNA, EB3 live imaging, domain-deletion localization, neuronal morphology quantification

    PMID:30018294

    Open questions at the time
    • Mechanism by which APC2 biases polarity at the molecular level not fully resolved
  22. 2018 Medium

    Defined the cortical actin association mechanism, requiring the N-terminal ASAD self-association domain and a C30 coiled-coil.

    Evidence Domain-deletion/mutagenesis in S2 cells, Drosophila ovary immunofluorescence, actin dynamics

    PMID:30019417

    Open questions at the time
    • Direct actin-binding partner versus indirect tethering not distinguished
  23. 2018 Medium

    Placed APC2 microtubule function downstream of regulatory inputs (Brat; mitochondria/actin/Fz-Axin modules) at axonal and dendritic microtubule plus ends, independent of canonical Wnt.

    Evidence Drosophila genetic epistasis, RNAi screens, live imaging of Apc2-GFP at branch points

    PMID:29602811 PMID:29617376

    Open questions at the time
    • Direct biochemical links between these upstream modules and APC2 not established
  24. 2020 High

    Demonstrated a postmitotic APC/C substrate function, with APC2 ubiquitinating DOK7 at K243 to regulate acetylcholine-receptor clustering at the NMJ.

    Evidence NMJ immunofluorescence, ubiquitination assay, K243/Y106 mutagenesis, AChR clustering

    PMID:32687671

    Open questions at the time
    • How the APC/C is activated in postmitotic myotubes not defined
  25. 2031 Medium

    Identified transcriptional control of APC2 by FOXO4, linking APC2 induction to β-catenin degradation and suppression of colorectal cancer metastasis.

    Evidence ChIP, APC2 knockdown rescue, migration/invasion assays, xenograft metastasis model

    PMID:34631691

    Open questions at the time
    • Single lab; mechanism of FOXO4-driven APC2 induction in normal tissue untested
  26. 2024 Medium

    Resolved a species-specific regulatory difference: yeast Apc2:Apc11 is pre-positioned for E2 binding in the apo state, unlike human APC/C requiring coactivator-induced rearrangement.

    Evidence Cryo-EM of apo and CDH1-bound yeast APC/C (preprint)

    PMID:bio_10.1101_2024.06.19.599685

    Open questions at the time
    • Preprint; functional consequence of the species difference not validated biochemically
  27. 2025 Medium

    Implicated Apc2 in spindle-assembly-checkpoint signaling through a BubR1 TPR-domain interaction within the MCC-APC/C complex.

    Evidence Cryo-EM of MCC-APC/C, BubR1 TPR mutational analysis (preprint)

    PMID:bio_10.1101_2025.10.13.682252

    Open questions at the time
    • Preprint; the specific contribution of the Apc2 contact to checkpoint kinetics not isolated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How APC2's distinct functional pools — APC/C catalytic subunit, destruction-complex scaffold, and microtubule/actin regulator — are partitioned and co-regulated within a single cell remains unresolved.
  • No quantitative partitioning of APC2 between mitotic, Wnt, and cytoskeletal complexes
  • Post-translational control directing APC2 to each pool undefined
  • Structural basis of microtubule and actin binding not determined at atomic resolution

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0060090 molecular adaptor activity 3 GO:0016874 ligase activity 2 GO:0098772 molecular function regulator activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005856 cytoskeleton 4 GO:0005886 plasma membrane 2 GO:0005794 Golgi apparatus 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-112316 Neuronal System 3 R-HSA-1640170 Cell Cycle 3 R-HSA-392499 Metabolism of proteins 2
Partners
APC11AXIN2CTNNB1DOK7TNKSTP53BP2
Complex memberships
APC/C (anaphase-promoting complex/cyclosome)β-catenin destruction complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Drosophila APC2 (dAPC2) binds Armadillo (β-catenin homolog) and acts as a negative regulator of Wingless (Wnt) signaling in the embryonic epidermis. Genetic epistasis places dAPC2 downstream of wg and upstream of arm, dTCF, and dishevelled. dAPC2 colocalizes with actin filaments and shows asymmetric localization in neuroblasts, suggesting cytoskeletal association. Genetic epistasis (loss-of-function allele), direct binding assay, immunolocalization The Journal of cell biology High 10491393
1998 Human APCL/APC2 protein contains five copies of the 20-amino-acid APC-repeat motif; this domain binds β-catenin and depletes the intracellular β-catenin pool. APC2 also regulates the interaction of β-catenin with TCF transcription factors, as shown by reporter-gene assay in APC-null colon carcinoma cells. Direct binding assay (20-aa repeat domain), reporter-gene (TOP-flash) transcriptional assay in APC-/- cells Cancer research Medium 9823329
1999 Mammalian APC2 contains two SAMP domains, both required for binding to conductin (Axin2). APC2 downregulates active β-catenin–TCF complex formation, as demonstrated by transient transcriptional activation assays in APC-null colon carcinoma cells. Domain-deletion binding analysis, transient transcriptional assay (TOP/FOP) in APC-/- cells Current biology : CB Medium 10021369
2001 APC2 and its binding partner Armadillo (β-catenin) localize to sites of cortical spindle attachment during syncytial mitoses in early Drosophila embryos. APC2–Armadillo complexes tether mitotic spindles to cortical actin. Zeste-white 3 kinase (GSK-3β homolog) phosphorylates APC and Armadillo and regulates the localization of APC2–Armadillo complexes, which is required for proper spindle positioning. Immunolocalization, live imaging, genetic loss-of-function (zw3/GSK-3 mutants), co-localization with actin/microtubule markers Nature cell biology High 11584277
2001 APC2 (the cullin subunit) and APC11 (the RING subunit) form a heterodimeric complex that constitutes the minimal ubiquitin ligase module of the human APC/C. This minimal module, together with Ubc4 or UbcH10, catalyzes ubiquitination of securin and cyclin B1 but lacks substrate specificity. APC11 and UbcH10 both bind the C-terminal cullin homology domain of APC2; Ubc4 interacts with APC11 directly. Baculoviral reconstitution of ubiquitin ligase activity in vitro, binding domain mapping, mutagenesis of APC11 Zn2+-binding residues Molecular biology of the cell High 11739784
1998 Budding yeast RSI1/APC2 is a subunit of the APC (anaphase-promoting complex). Temperature-sensitive rsi1/apc2 mutants arrest in metaphase, fail to degrade Clb2p, and cannot degrade securin (Pds1p); the anaphase block is suppressed by deletion of PDS1. Rsi1p/Apc2p co-immunoprecipitates with Cdc23p (another APC subunit). Temperature-sensitive genetic screen, epistasis (PDS1 deletion rescue), co-immunoprecipitation with Cdc23p The EMBO journal High 9430641
2002 Simultaneous loss of both Drosophila Apc1 and Apc2 causes global nuclear accumulation of Armadillo/β-catenin and constitutive activation of Wingless/Wnt transduction throughout development, demonstrating that the two proteins have redundant, global roles in restricting β-catenin-mediated transcription, even in tissues previously thought to rely only on one paralog. Genetic double-mutant epistasis, immunostaining for nuclear Armadillo, reporter assays Development (Cambridge, England) High 11923210
2002 Drosophila APC2 and APC1 have overlapping roles in regulating Wingless signaling in the embryonic epidermis and imaginal discs, despite striking differences in their intracellular localizations. Single mutants are often normal, but simultaneous elimination reveals functional redundancy. Genetic double-mutant analysis, immunostaining, transgenic rescue Developmental biology High 12297097 12297098
2002 In Drosophila larval neuroblasts, APC2 shows a highly dynamic, asymmetric cortical localization through the cell cycle, whereas APC1 localizes to centrosomes and microtubules. Despite different localizations, both play redundant roles in maintaining neuroblast numbers; the double mutant has severely reduced larval neuroblasts through a mechanism that does not involve Wg signaling misregulation, implicating cytoskeletal/adhesive APC functions. Immunolocalization, genetic double-mutant analysis, epistasis ruling out Wg pathway Developmental biology Medium 12297097
2002 Inversin interacts with the APC/C subunit APC2 via D-box motifs; site-directed mutagenesis of the conserved D-box residues in inversin abrogates this interaction, suggesting inversin is an APC2 target subject to APC/C-mediated degradation. Co-immunoprecipitation, site-directed mutagenesis of D-box motifs Human molecular genetics Medium 12471060
2000 APCL/APC2 binds p53-binding protein 2 (53BP2) via an interaction requiring both the SH3 domain and ankyrin-repeat domain of 53BP2 with the C-terminus of APCL. This binding translocates 53BP2 to the perinuclear region of mammalian cells; truncated APCL abrogates this co-localization, suggesting APC2 regulates the subcellular location of 53BP2. Yeast two-hybrid screen, in vitro binding assay, domain-mapping, confocal co-localization Cancer research Medium 10646860
2001 Human APC2 localizes to the Golgi apparatus and actin-containing structures (and occasionally microtubules) when overexpressed in SKOV3 cells; endogenous APC2 is diffusely cytoplasmic and colocalizes with Golgi and actin filaments. APC2 remains associated with actin filaments after cytochalasin D treatment, indicating it associates with actin through a direct or stable mechanism. Fluorescence microscopy, immunofluorescence, cytochalasin D treatment, FISH allelic imbalance analysis Cancer research Medium 11691822
2005 Cryo-EM 3D reconstruction of human and Xenopus APC/C mapped Cdh1 (coactivator) and Apc2 (cullin subunit) to the same side of the asymmetric complex, establishing that substrate ubiquitination occurs on this face. Cdh1 binding induces a conformational change in a large flexible APC/C domain, suggesting Cdh1 activates APC/C both by recruiting substrates and by conformational rearrangement. Cryo-EM angular reconstitution, random conical tilt (RCT), STEM mass measurement, antibody labeling for subunit mapping Molecular cell High 16364912
2009 APC2 is distributed along microtubules in growth cones and axon shafts of retinal axons. Overexpression of APC2 stabilizes microtubules; shRNA knockdown of APC2 in chick retinas reduces microtubule stability. APC2-knockdown retinal axons show reduced response to ephrin-A2 guidance cues and drastic alterations in retinotectal topographic projections in vivo. Immunohistochemistry, overexpression assay (microtubule stabilization), shRNA knockdown in chick retina, in vitro guidance assay, in vivo retinotectal projection analysis The Journal of neuroscience : the official journal of the Society for Neuroscience High 19759310
2011 Cortical localization of Drosophila APC2 requires both the Armadillo repeats and a novel C-terminal domain (neither alone is sufficient). The Armadillo repeats also mediate APC2 self-association. Cortical localization is required for APC2's role in organizing actin but is dispensable for its role in Wnt/Wingless signaling, as shown by rescue experiments with a C-terminal-deletion APC2. Domain-deletion analysis, S2 cell transfection, rescue assays in APC mutant embryos (actin and Wnt phenotypes), co-immunoprecipitation for self-association Journal of cell science High 21486956
2013 Loss of APC2 in Drosophila embryos leads to increased chromosome segregation errors through a cascade: incomplete centrosome separation → failure to inhibit ectopic cleavage furrows → mitotic defects and DNA damage. APC2 functions at the embryonic cortex together with Axin to promote mitotic fidelity through cytoskeletal regulation. Genetic loss-of-function, live imaging of chromosome segregation, epistasis with Axin, immunostaining for centrosome and furrow markers Development (Cambridge, England) High 24026117
2014 The spliceosome subunit SNW1 is required for correct splicing of APC2 pre-mRNA; SNW1 depletion reduces APC2 protein levels, decreases APC/C ubiquitin ligase activity, delays mitosis, and contributes to sister chromatid cohesion defects ('cohesion fatigue'). Simultaneous expression of sororin and APC2 from intron-less cDNAs restores cohesion in SNW1-depleted cells. siRNA knockdown, transcriptome-wide splicing analysis, intron-less cDNA rescue experiment, cohesion assays The EMBO journal High 25257309
2015 Loss-of-function mutation in APC2 causes Sotos syndrome-like features including impaired learning/memory and abnormal head shape in Apc2-/- mice, through loss of cytoskeletal regulation in neurons. APC2 is a downstream effector of NSD1: NSD1 knockdown downregulates Apc2 expression, and the neuronal migration/laminar positioning defect caused by Nsd1 knockdown is rescued by forced Apc2 expression. Mouse knockout, whole-exome sequencing (patient), Nsd1 knockdown in embryonic mouse brains, forced expression rescue, behavioral assays Cell reports High 25753423
2016 Tankyrase (TNKS) poly(ADP-ribose) polymerase binds a C-terminal RPQPSG motif in Drosophila APC2 (conserved in human APC2 but absent in human APC1). APC2 recruits TNKS into the β-catenin destruction complex. TNKS directly PARylates both Drosophila Axin and APC2, but PARylation does not globally regulate APC2 protein levels as it does for Axin. TNKS inhibition reduces β-catenin signaling through effects at both Axin and APC2. Yeast two-hybrid screen, co-immunoprecipitation, in vitro PARylation assay, motif-mapping, cell-based Wnt reporter assays with TNKS inhibitors The Journal of biological chemistry High 27068743
2018 APC2 promotes dynamics (plus-end growth) of minus-end-out microtubules in vertebrate dendrites and thereby regulates dendritic morphology. APC2 localizes as distinct clusters along microtubule bundles in dendrites; localization is driven by LC8-binding and two separate microtubule-interacting domains. APC2 depletion reduces plus-end dynamics of minus-end-out microtubules, increases microtubule sliding, and causes dendritic morphology defects. shRNA knockdown, live microtubule dynamics imaging (EB3 tracking), domain-deletion localization analysis, morphology quantification in neurons Nature communications High 30018294
2018 APC2 associates with the actin cortex through a multipart mechanism in Drosophila: cortical localization requires an N-terminal APC Self-Association Domain (ASAD) that mediates self-association, and a conserved coiled-coil within the C-terminal 30 amino acid (C30) domain. APC2 regulates cortical actin dynamics and distribution in Drosophila follicular epithelium and nurse cells. Domain-deletion and mutagenesis in S2 cells, immunofluorescence in Drosophila ovary, actin dynamics analysis Cytoskeleton (Hoboken, N.J.) Medium 30019417
2018 Drosophila Brain Tumor (Brat) acts cell-autonomously through its B-Box domains to regulate the expression and localization of Apc2 at the plus ends of microtubules in commissural axons. Brat and Apc2 promote axon growth across the midline independently of canonical Wnt/β-catenin transcriptional signaling, implicating Apc2 microtubule-stabilizing function in axon guidance. Genetic epistasis (Brat and Apc2 mutants), immunolocalization in commissural axons, genetic interaction analysis PLoS genetics Medium 29617376
2018 In Drosophila neurons, Apc2 localizes to dendrite branch points where it recruits Apc and thereby steers growing microtubule plus ends to maintain minus-end-out polarity. Apc2-GFP positioning at branch points requires energy production by mitochondria (spastin acts upstream of mitochondria), Nrg/Ank2, Arp2/3-mediated branched actin (downstream of Rac1), and a Fz/G-protein/Axin module. Candidate RNAi screen, secondary genetic screens, live imaging of Apc2-GFP at branch points, epistasis analysis G3 (Bethesda, Md.) Medium 29602811
2012 Drosophila Apc11 (lemmingA/LmgA) interacts with Morula/Apc2 and together they form a ternary complex with Vihar (the E2-C type ubiquitin-conjugating enzyme), establishing that the Apc11–Apc2 module recruits the E2 enzyme to the APC/C. Genetic complementation, immunoprecipitation/pull-down, yeast complementation assay Cell division Medium 22417125
2010 FBG1 (an SCF F-box protein) binds APC2 directly via a D-Box within the FBG1 F-box domain, as shown by immunoprecipitation and mutagenesis. Co-expression of FBG1 increases total APC2 protein levels but sequesters free APC2, inhibiting cell proliferation and inducing S-phase arrest. Co-immunoprecipitation, mutagenesis of D-box, flow cytometry (FACS) cell cycle analysis Cell cycle (Georgetown, Tex.) Medium 21135578
2020 APC2 (as APC/C subunit) is enriched at the postsynapse of neuromuscular junctions in postmitotic myotubes. In response to agrin stimulation, APC2 promotes ubiquitination of DOK7 at lysine 243, leading to its proteolytic degradation; this requires MuSK kinase activity and phosphorylation of tyrosine 106 in DOK7. This negatively regulates acetylcholine receptor clustering as part of NMJ homeostasis. Immunofluorescence at NMJ, ubiquitination assay, site-directed mutagenesis (K243, Y106), co-immunoprecipitation, AChR clustering assay FASEB journal : official publication of the Federation of American Societies for Experimental Biology High 32687671
2031 FOXO4 binds the APC2 gene promoter (shown by chromatin immunoprecipitation) to transcriptionally upregulate APC2 expression, which in turn increases phosphorylation and degradation of β-catenin, suppressing CRC cell migration and metastasis. APC2 knockdown reverses the anti-metastatic effects of FOXO4 overexpression. Chromatin immunoprecipitation (ChIP), APC2 knockdown rescue, cell migration/invasion assays, xenograft metastasis model Frontiers in cell and developmental biology Medium 34631691
2024 Cryo-EM structures of S. cerevisiae APC/C complexes show that the catalytic module (Apc2:Apc11) is already positioned to bind E2 enzyme in the apo-state (without coactivator), in contrast to human APC/C where coactivator binding induces a conformational change of Apc2:Apc11 to allow E2 binding. This identifies a species-specific regulatory mechanism for the Apc2-containing catalytic module. Cryo-EM structure determination (apo and CDH1-bound, phosphorylated and unphosphorylated S. cerevisiae APC/C) bioRxivpreprint Medium bio_10.1101_2024.06.19.599685
2025 The BubR1 TPR domain interacts with Apc2 (as well as Mad2 and Cdc20-APC/C). This interaction, identified by cryo-EM structure of the MCC-APC/C complex, contributes to MCC assembly and MCC-APC/C binding to enable rapid spindle assembly checkpoint signaling. Cryo-EM structure of MCC-APC/C complex, functional and biochemical analyses of BubR1 TPR domain mutations bioRxivpreprint Medium bio_10.1101_2025.10.13.682252

Source papers

Stage 0 corpus · 52 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Drosophila APC2 is a cytoskeletally-associated protein that regulates wingless signaling in the embryonic epidermis. The Journal of cell biology 162 10491393
2001 APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex. Molecular biology of the cell 156 11739784
2001 Drosophila APC2 and Armadillo participate in tethering mitotic spindles to cortical actin. Nature cell biology 142 11584277
2002 Expression analyses and interaction with the anaphase promoting complex protein Apc2 suggest a role for inversin in primary cilia and involvement in the cell cycle. Human molecular genetics 124 12471060
1999 Identification of APC2, a homologue of the adenomatous polyposis coli tumour suppressor. Current biology : CB 107 10021369
2019 Hsa_circ_0009361 acts as the sponge of miR-582 to suppress colorectal cancer progression by regulating APC2 expression. Clinical science (London, England : 1979) 99 31109967
1998 Identification of a brain-specific APC homologue, APCL, and its interaction with beta-catenin. Cancer research 90 9823329
2018 Overexpressing circular RNA hsa_circ_0002052 impairs osteosarcoma progression via inhibiting Wnt/β-catenin pathway by regulating miR-1205/APC2 axis. Biochemical and biophysical research communications 84 29852168
2002 Drosophila Apc1 and Apc2 regulate Wingless transduction throughout development. Development (Cambridge, England) 84 11923210
2005 Localization of the coactivator Cdh1 and the cullin subunit Apc2 in a cryo-electron microscopy model of vertebrate APC/C. Molecular cell 81 16364912
2002 Drosophila APC2 and APC1 have overlapping roles in the larval brain despite their distinct intracellular localizations. Developmental biology 57 12297097
2002 Drosophila APC2 and APC1 play overlapping roles in wingless signaling in the embryo and imaginal discs. Developmental biology 57 12297098
2015 MiR-939 promotes the proliferation of human ovarian cancer cells by repressing APC2 expression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 55 25960217
1998 Budding yeast RSI1/APC2, a novel gene necessary for initiation of anaphase, encodes an APC subunit. The EMBO journal 51 9430641
2019 circ-PKD2 inhibits carcinogenesis via the miR-204-3p/APC2 axis in oral squamous cell carcinoma. Molecular carcinogenesis 49 31206208
2014 SNW1 enables sister chromatid cohesion by mediating the splicing of sororin and APC2 pre-mRNAs. The EMBO journal 49 25257309
2015 Loss-of-Function Mutation in APC2 Causes Sotos Syndrome Features. Cell reports 37 25753423
2009 APC2 plays an essential role in axonal projections through the regulation of microtubule stability. The Journal of neuroscience : the official journal of the Society for Neuroscience 36 19759310
2000 APCL, a central nervous system-specific homologue of adenomatous polyposis coli tumor suppressor, binds to p53-binding protein 2 and translocates it to the perinucleus. Cancer research 35 10646860
2016 The Poly(ADP-ribose) Polymerase Enzyme Tankyrase Antagonizes Activity of the β-Catenin Destruction Complex through ADP-ribosylation of Axin and APC2. The Journal of biological chemistry 34 27068743
2020 SMYD2 suppresses APC2 expression to activate the Wnt/β-catenin pathway and promotes epithelial-mesenchymal transition in colorectal cancer. American journal of cancer research 30 32266106
2019 Panobinostat (LBH589) inhibits Wnt/β-catenin signaling pathway via upregulating APCL expression in breast cancer. Cellular signalling 30 30880222
2001 Human APC2 localization and allelic imbalance. Cancer research 30 11691822
2018 APC2 controls dendrite development by promoting microtubule dynamics. Nature communications 27 30018294
2016 Functional redundancy between Apc and Apc2 regulates tissue homeostasis and prevents tumorigenesis in murine mammary epithelium. Oncogene 25 27694902
2017 miR-4326 promotes lung cancer cell proliferation through targeting tumor suppressor APC2. Molecular and cellular biochemistry 24 29101731
2011 Cortical localization of APC2 plays a role in actin organization but not in Wnt signaling in Drosophila. Journal of cell science 24 21486956
2019 APC2 is critical for ovarian WNT signalling control, fertility and tumour suppression. BMC cancer 22 31291912
2019 microRNA-1205 promotes cell growth by targeting APC2 in lung adenocarcinoma. European review for medical and pharmacological sciences 20 30779081
2019 Bi-allelic Loss of Human APC2, Encoding Adenomatous Polyposis Coli Protein 2, Leads to Lissencephaly, Subcortical Heterotopia, and Global Developmental Delay. American journal of human genetics 20 31585108
2021 FOXO4 Inhibits the Migration and Metastasis of Colorectal Cancer by Regulating the APC2/β-Catenin Axis. Frontiers in cell and developmental biology 18 34631691
2013 APC2 and Axin promote mitotic fidelity by facilitating centrosome separation and cytoskeletal regulation. Development (Cambridge, England) 16 24026117
2015 Overexpression of lipocalins and pro-inflammatory chemokines and altered methylation of PTGS2 and APC2 in oral squamous cell carcinomas induced in rats by 4-nitroquinoline-1-oxide. PloS one 15 25635769
2015 The expression pattern of APC2 and APC7 in various cancer cell lines and AML patients. Advances in medical sciences 15 26046517
2017 Subtle Deregulation of the Wnt-Signaling Pathway Through Loss of Apc2 Reduces the Fitness of Intestinal Stem Cells. Stem cells (Dayton, Ohio) 14 29027285
2023 Recessive APC2 missense variants associated with epilepsies without neurodevelopmental disorders. Seizure 10 37657306
2018 Identification of Proteins Required for Precise Positioning of Apc2 in Dendrites. G3 (Bethesda, Md.) 10 29602811
2018 Brain Tumor promotes axon growth across the midline through interactions with the microtubule stabilizing protein Apc2. PLoS genetics 10 29617376
2017 Hsa-miR-11181 regulates Wnt signaling pathway through targeting of APC2 transcripts in SW480 cell line. Gene 10 29111205
2002 Expression of Apc2 during mouse development. Brain research. Gene expression patterns 10 15018807
2020 APC2CDH1 negatively regulates agrin signaling by promoting the ubiquitination and proteolytic degradation of DOK7. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 9 32687671
2020 An LCI-like protein APC2 protects ginseng root from Fusarium solani infection. Journal of applied microbiology 8 32639629
2018 Hypermethylation of APC2 Is a Predictive Epigenetic Biomarker for Chinese Colorectal Cancer. Disease markers 8 30510602
2012 lemmingA encodes the Apc11 subunit of the APC/C in Drosophila melanogaster that forms a ternary complex with the E2-C type ubiquitin conjugating enzyme, Vihar and Morula/Apc2. Cell division 8 22417125
1999 Analysis of APCL, a brain-specific adenomatous polyposis coli homologue, for mutations and expression in brain tumors. Japanese journal of cancer research : Gann 8 10551328
2016 APC2 and CYP1B1 methylation changes in the bone marrow of acute myeloid leukemia patients during chemotherapy. Experimental and therapeutic medicine 7 27882114
2010 FBG1 is a promiscuous ubiquitin ligase that sequesters APC2 and causes S-phase arrest. Cell cycle (Georgetown, Tex.) 7 21135578
2018 APC2 associates with the actin cortex through a multipart mechanism to regulate cortical actin organization and dynamics in the Drosophila ovary. Cytoskeleton (Hoboken, N.J.) 5 30019417
2024 Reprint of: Recessive APC2 missense variants associated with epilepsies without neurodevelopmental disorders. Seizure 4 38523034
2022 Methylation of APC2, NR3C1, and DRD2 gene promoters in turkish patients with tobacco use disorder. Nigerian journal of clinical practice 2 35170441
2021 High miR-3648 expression and low APC2 expression are associated with shorter survival and tumor progression in NSCLC. Histology and histopathology 2 34927228
2026 Human papillomavirus16 E7 enhances cell stemness by regulating the APC2/SPIN4/β-catenin axis in cervical cancer. Oncogenesis 0 41730837

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