Affinage

APC

Adenomatous polyposis coli protein · UniProt P25054

Round 2 corrected
Length
2843 aa
Mass
311.6 kDa
Annotated
2026-04-28
130 papers in source corpus 35 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

APC is a multifunctional tumor suppressor that serves as the central scaffold of the β-catenin destruction complex, recruiting Axin, GSK-3β, and CKIα to drive sequential phosphorylation of β-catenin at Ser45 (CKIα priming) and subsequent GSK-3β sites, thereby licensing β-TrCP-mediated ubiquitination and proteasomal degradation of β-catenin and suppressing Wnt/TCF target gene transcription—most critically c-Myc, which is the essential downstream effector of APC-loss-driven intestinal neoplasia (PMID:9601641, PMID:11955436, PMID:22682247, PMID:17377531). Germline truncating mutations in APC cause familial adenomatous polyposis (FAP), and somatic APC truncations—clustered in the mutation cluster region of exon 15—are found in >80% of sporadic colorectal cancers (PMID:1651174, PMID:1338904). Beyond Wnt regulation, APC localizes to microtubule plus-ends via its C-terminal EB1-binding domain, contributes to kinetochore–microtubule attachment and the spindle assembly checkpoint through a BubR1–EB1 ternary complex, and coordinates actin-based protrusion during polarized cell migration (PMID:10662776, PMID:17709426, PMID:19928352, PMID:35483122). APC also shuttles into the nucleus where it represses β-catenin/TCF transcription via CtBP interaction and participates in DNA base excision repair through associations with DNA polymerase β and Fen-1 (PMID:19928349, PMID:18662849).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1991 High

    Positional cloning of the APC gene at 5q21 and identification of truncating germline mutations in FAP patients established APC as the causal tumor suppressor for hereditary colorectal polyposis.

    Evidence Positional cloning and SSCP/DNA sequencing in FAP kindreds and sporadic colorectal cancers

    PMID:1651174 PMID:1651562 PMID:1651563 PMID:1678319

    Open questions at the time
    • Protein function was unknown at the time of cloning
    • Mechanism linking APC loss to tumorigenesis was entirely undefined
  2. 1993 High

    Discovery that APC directly binds β-catenin through 15-amino-acid repeats provided the first molecular link between APC and the cell adhesion/signaling machinery, reframing APC as a regulator of catenin biology rather than a conventional growth-factor pathway component.

    Evidence Reciprocal co-immunoprecipitation and peptide mapping in epithelial cell lines

    PMID:8259518 PMID:8259519

    Open questions at the time
    • Whether APC regulated β-catenin levels or only its adhesive function was unresolved
    • Kinase and ubiquitin-ligase components of the pathway were unknown
  3. 1995 High

    Identification of EB1 as an APC C-terminal binding partner revealed a second functional axis—microtubule plus-end association—distinct from the β-catenin regulatory role.

    Evidence Yeast two-hybrid, in vitro binding, and co-immunoprecipitation

    PMID:7606712

    Open questions at the time
    • Functional consequence of APC–EB1 interaction for cell division was undefined
    • Whether the C-terminus was relevant to tumor suppression remained unclear
  4. 1996 High

    Demonstration that GSK-3β phosphorylates APC and that this phosphorylation is required for high-affinity β-catenin binding established the enzymatic logic of the destruction complex—kinase activity modulates the scaffold's ability to capture its substrate.

    Evidence In vitro kinase assay, phosphorylation site mapping, co-immunoprecipitation

    PMID:8638126

    Open questions at the time
    • The scaffold protein Axin had not yet been placed in the complex
    • Priming kinase upstream of GSK-3β was unknown
  5. 1998 High

    Identification of Axin as the central scaffold that directly binds APC, β-catenin, and GSK-3β, and dramatically enhances GSK-3β-dependent phosphorylation, completed the core architecture of the destruction complex.

    Evidence Reconstituted quaternary complex with purified components, co-immunoprecipitation from cells, in vitro kinase assays

    PMID:9482734 PMID:9601641

    Open questions at the time
    • Priming phosphorylation step was still missing
    • Ubiquitin-ligase link to proteasomal degradation was not yet defined
  6. 2002 High

    Identification of CKIα as the priming kinase that phosphorylates β-catenin at Ser45 within the Axin-bound complex, prerequisite for GSK-3β processivity, completed the dual-kinase phosphorylation cascade and explained how Wnt signaling blocks the initial trigger of β-catenin degradation.

    Evidence In vitro kinase assay, mass spectrometry, phospho-specific antibodies, Xenopus embryo depletion

    PMID:11955436 PMID:12000790

    Open questions at the time
    • How Wnt signaling mechanistically inhibits destruction complex output was still debated
    • Structural basis for CKIα priming within the complex was unknown
  7. 2007 High

    Genetic epistasis showing that simultaneous Myc deletion rescues the proliferative and differentiation defects of Apc loss in intestinal epithelium established c-Myc as the critical transcriptional effector of Wnt pathway activation downstream of APC, defining the key oncogenic output of APC mutations.

    Evidence Conditional double-knockout mouse model with histological and transcriptomic phenotyping

    PMID:17377531

    Open questions at the time
    • Whether Myc dependence extends to late-stage carcinomas was untested
    • Additional Wnt targets contributing to full malignant progression were not excluded
  8. 2007 High

    Reconstitution of a BubR1–APC–EB1 ternary complex and demonstration that BubR1 phosphorylates APC to regulate kinetochore–microtubule attachments established a mitotic function for APC separate from Wnt signaling, linking APC truncation to chromosomal instability.

    Evidence Xenopus egg extract immunodepletion, in vitro kinase assay, purified ternary complex

    PMID:17709426

    Open questions at the time
    • Relative contribution of chromosomal instability versus Wnt activation to tumorigenesis was unresolved
    • APC phosphorylation sites by BubR1 and their structural consequences were not mapped
  9. 2012 High

    Demonstration that Wnt signaling does not disassemble the destruction complex but instead suppresses β-catenin ubiquitination within an intact complex—causing its saturation and accumulation of free cytosolic β-catenin—fundamentally revised the model of how APC/Axin regulate β-catenin flux.

    Evidence Endogenous immunoprecipitation, phosphorylation and ubiquitination assays, proteasome inhibition, intestinal organoids

    PMID:22682247

    Open questions at the time
    • Molecular mechanism by which Wnt inhibits the ubiquitination step within the intact complex remains structurally unresolved
    • Whether saturation model applies equivalently across all tissue types is untested
  10. 2021 High

    Single-molecule imaging revealed KIF1C-dependent transport of APC-associated mRNAs to cytoplasmic protrusions via 3′UTR-encoded signals, establishing a post-transcriptional logistics role for APC in polarized mRNA localization beyond its canonical protein-level functions.

    Evidence Live two-color single-molecule imaging, RNA immunoprecipitation, siRNA knockdown, 3′UTR sufficiency assay

    PMID:34493599

    Open questions at the time
    • Whether APC protein itself directly contacts the mRNA or acts through adaptor proteins is unclear
    • Functional consequences of mRNA mislocalization in APC-mutant tumors are not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structural model of the full destruction complex—showing how APC, Axin, CKIα, GSK-3β, and β-TrCP coordinate β-catenin capture, processivity of dual phosphorylation, and handoff to the ubiquitin ligase—remains unavailable, limiting mechanistic understanding of how specific APC truncations differentially affect complex activity.
  • No full-length APC structure exists
  • How APC truncation positions (MCR variations) quantitatively alter destruction complex output is undefined
  • Relative contributions of chromosomal instability, Wnt deregulation, and BER deficiency to APC-driven tumorigenesis are not quantitatively partitioned

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 5 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4
Localization
GO:0005856 cytoskeleton 4 GO:0005829 cytosol 3 GO:0005886 plasma membrane 3 GO:0005634 nucleus 2 GO:0005635 nuclear envelope 2 GO:0005815 microtubule organizing center 2
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1643685 Disease 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-1640170 Cell Cycle 2 R-HSA-5357801 Programmed Cell Death 1 R-HSA-73894 DNA Repair 1
Partners
AXIN1BUBR1CSNK1A1CTBP1CTNNB1GSK3BMAPRE1NUP358
Complex memberships
APC–EB1–BubR1 kinetochore complexβ-catenin destruction complex (APC/Axin/GSK-3β/CKIα)

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 The APC gene was identified at chromosome 5q21, found to be mutated in familial adenomatous polyposis (FAP) patients and in sporadic colorectal cancer; the gene encodes an unusually large protein predicted to contain coiled-coil regions. Positional cloning, SSCP mutation analysis, DNA sequencing Cell / Science High 1651174 1651562 1651563 1678319
1992 Somatic mutations in APC in colorectal tumors cluster within a small region of exon 15 (mutation cluster region, MCR), and >95% result in truncation of the APC protein; over 80% of colorectal tumors carry at least one APC mutation. DNA sequencing of tumor samples, LOH analysis Human molecular genetics High 1338904
1993 APC protein associates with beta-catenin (a 95 kDa protein that binds E-cadherin) in cells, as demonstrated by co-immunoprecipitation with APC antibodies, suggesting APC is involved in cell adhesion. Co-immunoprecipitation, protein purification, peptide sequencing Science High 8259518 8259519
1993 APC associates with both alpha-catenin and beta-catenin via a 27-residue fragment containing a 15-amino acid repeat of APC, revealing a direct structural link between APC, the catenins, and cell adhesion machinery. Co-immunoprecipitation, peptide mapping, nucleotide sequence analysis Science High 8259519
1993 Full-length APC (~300 kDa) is expressed in normal cells, whereas colorectal tumor cells predominantly express truncated APC proteins lacking the C-terminus; APC localizes to the cytoplasm with more intense basolateral staining in the upper portions of colonic crypts, suggesting increased expression with cell maturation. Western blot with monoclonal/polyclonal antibodies, immunohistochemistry Proceedings of the National Academy of Sciences High 8385345
1994 E-cadherin and APC directly compete for binding to the internal armadillo-like repeats of beta-catenin; the NH2-terminal domain of beta-catenin then mediates cytoskeletal interaction via alpha-catenin, establishing that APC forms cell-junction-like complexes and that beta-catenin is a central regulator of both adhesion and tumor suppression. In vitro binding assays, co-immunoprecipitation, competition experiments The Journal of cell biology High 7806582
1995 APC binds to the novel protein EB1 (a 268-amino acid protein with yeast homolog) through the carboxyl terminus of APC, as confirmed by two-hybrid screening, in vitro binding assays, and co-immunoprecipitation with anti-EB1 antibodies in vivo. Yeast two-hybrid, in vitro binding assay, co-immunoprecipitation Cancer research High 7606712
1996 APC binds to GSK3beta when beta-catenin is present in excess; APC is a substrate for GSK3beta in vitro and phosphorylation sites were mapped to the central region of APC; phosphorylation by GSK3beta of this central region is required for beta-catenin binding to that region, establishing APC as part of the beta-catenin destruction complex. Co-immunoprecipitation, in vitro kinase assay, phosphorylation site mapping Science High 8638126
1996 Inducible expression of APC in colorectal cancer cells containing only inactive endogenous APC alleles causes substantial reduction in cell growth through induction of apoptosis, establishing a direct tumor-suppressive function for APC via programmed cell death. Inducible expression system, cell growth assay, apoptosis assay Proceedings of the National Academy of Sciences High 8755583
1998 Human Axin binds directly to beta-catenin, GSK3beta, and APC in vitro; endogenous proteins form a complex in cells; Axin binding sites on APC map to a region deleted in cancer; Axin acts as a scaffold to coordinate APC, beta-catenin and GSK3beta, and dramatically facilitates GSK3beta-dependent phosphorylation of APC and beta-catenin. In vitro binding assays, co-immunoprecipitation from cells, overexpression/phosphorylation assays Current biology High 9601641
1998 Axin forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin; APC is integral to this complex through direct interaction with Axin's APC-binding domain. Yeast two-hybrid, in vitro binding assay, co-immunoprecipitation, in vitro kinase assay The EMBO journal High 9482734
1999 Beta-TrCP F-box protein binds directly to phosphorylated beta-catenin (phosphorylated at GSK3beta sites) and is a component of an E3 ubiquitin ligase responsible for targeted degradation of beta-catenin downstream of the APC/Axin/GSK3beta complex. Co-immunoprecipitation, direct binding assay, overexpression/dominant-negative experiments Current biology High 10074433
2000 APC protein moves along microtubules and concentrates as granules at their growing plus-ends in epithelial cells during cell spreading and wound healing; when MTs shorten, APC granules drop off the ends; the COOH-terminal region targets APC to growing MT ends, while the region lacking COOH-terminus forms granules that move along MTs in an ATP-dependent manner. GFP-fusion live cell imaging, deletion mutant analysis, immunoelectron microscopy The Journal of cell biology High 10662776
2001 Crystal structure of the beta-catenin arm repeat domain in complex with E-cadherin cytoplasmic domain reveals that APC contains sequences homologous to the phosphorylated region of E-cadherin, suggesting APC competes with E-cadherin for an overlapping binding surface on beta-catenin in a phosphorylation-dependent manner. X-ray crystallography with functional mutant validation Cell High 11348595
2002 CKIalpha (casein kinase Ialpha) is an Axin-associated kinase that phosphorylates beta-catenin at Ser45 as a priming event required for subsequent GSK-3beta phosphorylation; this dual-kinase mechanism within the APC/Axin destruction complex initiates the beta-catenin phosphorylation-degradation cascade, and Wnt signaling suppresses the CKIalpha priming step. In vitro kinase assay, mass spectrometry, phospho-specific antibodies, depletion experiments in Xenopus embryos Cell / Genes & development High 11955436 12000790
2002 APC protein shuttles between multiple subcellular destinations including the cytoplasm, plasma membrane, microtubule plus-ends at the cell leading edge, and the nucleus, with each localization linked to distinct cellular functions including Wnt signaling regulation, cell migration, and chromosome stability. Immunofluorescence, GFP-tagging, fractionation studies (review of multiple experimental papers) Nature reviews. Molecular cell biology High 11988767
2007 Simultaneous deletion of both Apc and Myc in the adult murine small intestine rescues the perturbed differentiation, migration, proliferation and apoptosis phenotypes caused by Apc loss alone, despite high nuclear beta-catenin levels; Myc is required for the majority of Wnt target gene activation following Apc loss, establishing Myc as the critical downstream mediator of early Apc-loss-driven neoplasia. Conditional double-knockout mouse model (in vivo deletion), array analysis, histological and cell biological phenotyping Nature High 17377531
2007 BubR1 kinetochore kinase interacts with APC and EB1 in Xenopus egg extracts; BubR1 directly phosphorylates APC in vitro and forms a ternary complex with APC and microtubules; immunodepletion shows BubR1 kinase activity is essential for chromosome positioning at the metaphase plate, and this requires APC/EB1 complex formation for stable kinetochore-microtubule attachment. Xenopus egg extract immunodepletion, antibody addition, purified component reconstitution, in vitro kinase assay The Journal of cell biology High 17709426
2007 Prostate-specific deletion of Apc in mice causes fully penetrant prostate hyperplasia and adenocarcinoma associated with elevated beta-catenin protein levels and high proliferation, demonstrating that APC loss-mediated Wnt/beta-catenin activation is sufficient to drive prostate carcinogenesis. Conditional Cre-mediated knockout (probasin-Cre), histopathology, immunohistochemistry Cancer research High 17363566
2008 APC interacts with nuclear pore complex protein Nup153 (nucleoporin 153) through its middle region, and this interaction promotes association of microtubules with the nuclear membrane; this function is required for polarization of the microtubule cytoskeleton during directional cell migration. Co-immunoprecipitation, GFP-localization, dominant-negative expression, scratch-wound migration assay Biology of the cell Medium 18042042
2008 APC regulates DNA base excision repair (BER) through interaction with DNA polymerase beta (Pol-beta) and flap endonuclease 1 (Fen-1), and APC gene transcription is activated by alkylating agents, suggesting APC modulates whether DNA-damaged cells survive or undergo apoptosis. Interaction assays, BER activity measurement, transcriptional induction assays (review synthesizing experimental data) Cancer letters Medium 18662849
2009 APC associates with mitotic spindle microtubules at their plus-ends at kinetochores; genetic and functional experiments show APC regulates spindle microtubule dynamics through EB1 interaction; APC is required for the spindle checkpoint to detect transiently misaligned chromosomes; truncated APC alleles act dominantly to inhibit the mitotic spindle, placing chromosome instability at the earliest stage of colorectal cancer. Immunofluorescence, genetic epistasis in yeast and mammalian cells, dominant-negative expression, spindle checkpoint assays Advances in experimental medicine and biology High 19928352
2009 Nup358 (RanBP2) interacts with the middle region of APC (a region with microtubule plus-end-targeting activity), cooperates with kinesin-2 in a nuclear-transport-independent mechanism to regulate APC localization to the cell cortex, and is required for polarized cell migration as shown by RNAi knockdown in wound-healing assays. Co-immunoprecipitation, ectopic expression, RNAi knockdown, scratch-wound migration assay, MT plus-end tracking Journal of cell science Medium 19654215
2009 Nuclear APC contains two classical nuclear localization signals and nuclear export signals enabling shuttling between nucleus and cytoplasm; nuclear APC opposes beta-catenin-mediated transcription through nuclear sequestration of beta-catenin and interaction with transcriptional corepressor CtBP; additional nuclear partners include AP-2alpha, Crm1, PTP-BL, DNA polymerase beta, and PCNA. NLS/NES mapping, nuclear import/export assays, co-immunoprecipitation, transcription reporter assays Advances in experimental medicine and biology High 19928349
2010 Microflora-MyD88-ERK signaling in intestinal epithelial cells promotes tumorigenesis in Apc(min/+) mice by phosphorylating c-Myc to prevent its ubiquitination and proteasomal degradation; Apc(min/+)/Myd88(-/-) mice have lower p-ERK and fewer/smaller tumors; ERK inhibitor suppresses tumorigenesis, establishing a microflora-TLR-ERK-Myc axis downstream of Apc loss. Genetic epistasis (double knockout), biochemical phosphorylation assay, pharmacological inhibition, in vivo tumor analysis Nature medicine High 20473309
2012 Wnt signaling does not disassemble the APC/Axin1 destruction complex nor inhibit phosphorylation of Axin1-bound beta-catenin; instead, Wnt suppresses beta-catenin ubiquitination within an intact complex, leading to complex saturation by phospho-beta-catenin, so that newly synthesized beta-catenin accumulates in free cytosolic form and engages nuclear TCF factors. Endogenous protein immunoprecipitation, phosphorylation assays, ubiquitination assays, proteasome inhibition, intestinal organoids Cell High 22682247
2013 APC regulates the miR-17-92 cluster through the beta-catenin pathway: activated beta-catenin resulting from APC loss binds to and activates the miR-17-92 promoter; enforced expression of miR-19a overrides APC tumor suppressor activity, and knockdown of miR-19a reduces aggressive features in cells with compromised APC. APC-inducible cell line, miRNA array, ChIP, promoter reporter assay, miRNA overexpression/knockdown Oncogene Medium 26804172
2013 Phosphorylated beta-catenin preferentially binds to the 15 amino acid repeats (15R) of APC rather than the first 20 amino acid repeat, suggesting the 15R region constitutes a gate connecting beta-catenin phosphorylation and subsequent ubiquitination/degradation; truncated APC in colorectal tumors almost always retains at least one 15R, and APCL (APC2 paralog) uses the 15R of truncated APC via heterodimerization to target beta-catenin for degradation. RNA interference, domain-swap experiments, co-immunoprecipitation, beta-catenin degradation assays PloS one Medium 23840886
2021 METTL3 upregulates m6A modification of APC mRNA, which recruits YTHDF protein to promote APC mRNA degradation; reduced APC expression then increases beta-catenin and downstream targets (cyclin D1, c-Myc, PKM2), promoting aerobic glycolysis and tumor formation in esophageal squamous cell carcinoma. m6A-RIP sequencing, RNA immunoprecipitation, METTL3 knockdown/overexpression, YTHDF binding assay, xenograft mouse model Nature communications High 34155197
2021 The kinesin motor KIF1C interacts with APC-dependent mRNAs and is required for their transport to cytoplasmic protrusions; live two-color imaging directly shows single mRNAs transported by single KIF1C motors; the 3'UTR of APC-dependent mRNAs is sufficient to trigger KIF1C-dependent transport, and KIF1C also clusters these mRNAs at the periphery. RNA immunoprecipitation, live single-molecule imaging (two-color), siRNA knockdown, 3'UTR sufficiency assay RNA High 34493599
2022 APC regulates both actin and microtubule cytoskeletons during cell migration; APC at microtubule plus-ends can stimulate Arp2/3 complex-dependent nucleation of branched actin filament networks via intermediate signaling events, linking microtubule dynamics to leading-edge protrusion through APC as an intermediate. Live-cell imaging, FRAP, actin nucleation assays, loss-of-function experiments (review integrating experimental data) European journal of cell biology Medium 35483122

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
1991 Identification and characterization of the familial adenomatous polyposis coli gene. Cell 2411 1651174
1991 Identification of FAP locus genes from chromosome 5q21. Science (New York, N.Y.) 2071 1651562
2013 ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genetics in medicine : official journal of the American College of Medical Genetics 1945 23788249
2002 Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 1758 11955436
1991 Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science (New York, N.Y.) 1669 1651563
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nature biotechnology 1336 16964243
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
1996 Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly. Science (New York, N.Y.) 1275 8638126
1993 Association of the APC gene product with beta-catenin. Science (New York, N.Y.) 1202 8259518
1993 Association of the APC tumor suppressor protein with catenins. Science (New York, N.Y.) 1142 8259519
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
1998 Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin. The EMBO journal 1086 9482734
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2011 Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation. Nature 920 22056988
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2000 DNA cloning using in vitro site-specific recombination. Genome research 815 11076863
1995 The molecular basis of Turcot's syndrome. The New England journal of medicine 770 7661930
1998 Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta. Current biology : CB 739 9601641
2012 Wnt signaling through inhibition of β-catenin degradation in an intact Axin1 complex. Cell 734 22682247
1991 Identification of deletion mutations and three new genes at the familial polyposis locus. Cell 716 1678319
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2001 The ABC of APC. Human molecular genetics 692 11257105
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2001 The structure of the beta-catenin/E-cadherin complex and the molecular basis of diverse ligand recognition by beta-catenin. Cell 653 11348595
1992 Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene. Human molecular genetics 651 1338904
2002 Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway. Genes & development 610 12000790
2003 Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent beta-catenin degradation. The Journal of cell biology 607 12952940
1999 The F-box protein beta-TrCP associates with phosphorylated beta-catenin and regulates its activity in the cell. Current biology : CB 599 10074433
1994 E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton. The Journal of cell biology 585 7806582
2007 Myc deletion rescues Apc deficiency in the small intestine. Nature 504 17377531
1996 Apoptosis and APC in colorectal tumorigenesis. Proceedings of the National Academy of Sciences of the United States of America 439 8755583
1993 The APC gene product in normal and tumor cells. Proceedings of the National Academy of Sciences of the United States of America 428 8385345
1995 APC binds to the novel protein EB1. Cancer research 392 7606712
2008 Macrophages as APC and the dendritic cell myth. Journal of immunology (Baltimore, Md. : 1950) 380 18941170
1997 The adenomatous polyposis coli (APC) tumor suppressor. Biochimica et biophysica acta 375 9196022
2007 Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene. Journal of cell science 364 17881494
2002 The APC gene in colorectal cancer. European journal of cancer (Oxford, England : 1990) 296 11978510
2002 Regulation of APC-Cdc20 by the spindle checkpoint. Current opinion in cell biology 289 12473343
2008 Regulation of APC/C activators in mitosis and meiosis. Annual review of cell and developmental biology 256 18598214
2000 Adenomatous polyposis coli (APC) protein moves along microtubules and concentrates at their growing ends in epithelial cells. The Journal of cell biology 244 10662776
2001 Aberrant methylation of the adenomatous polyposis coli (APC) gene promoter 1A in breast and lung carcinomas. Clinical cancer research : an official journal of the American Association for Cancer Research 220 11448917
2002 The subcellular destinations of APC proteins. Nature reviews. Molecular cell biology 206 11988767
2005 Activation of the prostaglandin D2 receptor DP2/CRTH2 increases allergic inflammation in mouse. Journal of immunology (Baltimore, Md. : 1950) 174 15749909
2010 ERK activation drives intestinal tumorigenesis in Apc(min/+) mice. Nature medicine 167 20473309
2013 Panta rhei: the APC/C at steady state. The Journal of cell biology 165 23589490
2008 Atypical E2F activity restrains APC/CCCS52A2 function obligatory for endocycle onset. Proceedings of the National Academy of Sciences of the United States of America 145 18787127
2021 METTL3 promotes tumour development by decreasing APC expression mediated by APC mRNA N6-methyladenosine-dependent YTHDF binding. Nature communications 140 34155197
2006 Precise destruction: an emerging picture of the APC. Genes & development 134 17114580
2002 APC/Fizzy-Related targets Aurora-A kinase for proteolysis. EMBO reports 134 11964384
2008 Apc mice: models, modifiers and mutants. Pathology, research and practice 126 18538487
1997 Carcinogenesis: a balance between beta-catenin and APC. Current biology : CB 126 9210368
2014 APC(Cdc20) suppresses apoptosis through targeting Bim for ubiquitination and destruction. Developmental cell 124 24871945
2016 Mechanism of APC/CCDC20 activation by mitotic phosphorylation. Proceedings of the National Academy of Sciences of the United States of America 118 27114510
1999 Regulation of APC activity by phosphorylation and regulatory factors. The Journal of cell biology 118 10459014
2008 To cell cycle, swing the APC/C. Biochimica et biophysica acta 114 18544349
2001 Adenomatous polyposis coli (APC) gene promoter hypermethylation in primary breast cancers. British journal of cancer 114 11437404
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
2017 Combined Mutation of Apc, Kras, and Tgfbr2 Effectively Drives Metastasis of Intestinal Cancer. Cancer research 111 29282223
1996 Somatic mutations of the APC gene in sporadic hepatoblastomas. Cancer research 107 8764128
2010 Crystal structure of HLA-DP2 and implications for chronic beryllium disease. Proceedings of the National Academy of Sciences of the United States of America 95 20356827
2013 AMPKα1 deficiency amplifies proinflammatory myeloid APC activity and CD40 signaling. Journal of leukocyte biology 94 23883517
2005 Determinants of the APTT- and ETP-based APC sensitivity tests. Journal of thrombosis and haemostasis : JTH 93 15978106
2005 Non-traditional roles for the Adenomatous Polyposis Coli (APC) tumor suppressor protein. Gene 90 16185824
2000 The adenomatous polyposis coli (APC) tumour suppressor--genetics, function and disease. Molecular medicine today 89 11099951
1995 Cloning and characterization of human DP2, a novel dimerization partner of E2F. Oncogene 85 7784053
2009 APC resistance: biological basis and acquired influences. Journal of thrombosis and haemostasis : JTH 84 20002539
2007 Inactivation of Apc in the mouse prostate causes prostate carcinoma. Cancer research 82 17363566
2011 Mutual regulation between the spindle checkpoint and APC/C. Seminars in cell & developmental biology 80 21439394
2007 Adenomatous polyposis coli (APC) plays multiple roles in the intestinal and colorectal epithelia. Medical molecular morphology 79 17572842
2008 APC shuttling to the membrane, nucleus and beyond. Trends in cell biology 76 18848448
1997 APC gene mutations and extraintestinal phenotype of familial adenomatous polyposis. Gut 76 9176082
1995 Biallelic inactivation of the APC gene in hepatoblastoma. Cancer research 75 7585543
2019 APC/C: current understanding and future perspectives. F1000Research 74 31164978
2009 Complete deletion of Apc results in severe polyposis in mice. Oncogene 70 20010873
2016 Olfactomedin 4 deletion induces colon adenocarcinoma in ApcMin/+ mice. Oncogene 68 26973250
2004 APC promoter hypermethylation contributes to the loss of APC expression in colorectal cancers with allelic loss on 5q. Cancer biology & therapy 66 15326380
2014 Expansion of the APC superfamily of secondary carriers. Proteins 62 25043943
2003 Mechanisms of ganglioside inhibition of APC function. Journal of immunology (Baltimore, Md. : 1950) 60 12902465
2003 15R-methyl-prostaglandin D2 is a potent and selective CRTH2/DP2 receptor agonist in human eosinophils. The Journal of pharmacology and experimental therapeutics 55 12490611
2002 Identification of HLA-DP3-restricted peptides from EBNA1 recognized by CD4(+) T cells. Cancer research 54 12499257
2001 Where is APC going? The Journal of cell biology 54 11564752
2018 PGD2/DP2 receptor activation promotes severe viral bronchiolitis by suppressing IFN-λ production. Science translational medicine 53 29743346
2013 PIK3CA and APC mutations are synergistic in the development of intestinal cancers. Oncogene 53 23708654
2007 BubR1 and APC/EB1 cooperate to maintain metaphase chromosome alignment. The Journal of cell biology 52 17709426
2017 The role of APC in WNT pathway activation in serrated neoplasia. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 49 29148535
2008 Original CIN: reviewing roles for APC in chromosome instability. The Journal of cell biology 48 18519734
2014 Prostaglandin D2 and the role of the DP1, DP2 and TP receptors in the control of airway reflex events. The European respiratory journal 47 25323233
2013 The spindle checkpoint, APC/C(Cdc20), and APC/C(Cdh1) play distinct roles in connecting mitosis to S phase. The Journal of cell biology 47 23775192
2014 Expression of DP2 (CRTh2), a prostaglandin D₂ receptor, in human mast cells. PloS one 46 25268140
2009 Genetic mechanisms in Apc-mediated mammary tumorigenesis. PLoS genetics 46 19197353
2008 A novel function of adenomatous polyposis coli (APC) in regulating DNA repair. Cancer letters 46 18662849
2016 Adenomatous polyposis coli (APC) regulates miR17-92 cluster through β-catenin pathway in colorectal cancer. Oncogene 45 26804172
2004 Prolonged antigen presentation, APC-, and CD8+ T cell turnover during mycobacterial infection: comparison with Listeria monocytogenes. Journal of immunology (Baltimore, Md. : 1950) 45 15004149
2015 Arid1a inactivation in an Apc- and Pten-defective mouse ovarian cancer model enhances epithelial differentiation and prolongs survival. The Journal of pathology 44 26279473
2002 No evidence for involvement of beta-catenin and APC in urothelial carcinomas. International journal of oncology 44 11956582
2005 Adenomatous polyposis coli (Apc) tumor suppressor gene as a multifunctional gene. Anatomical science international 43 16158975
2003 Cadherins, catenins and APC in pleural malignant mesothelioma. The Journal of pathology 43 14595746
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2009 APC in cell migration. Advances in experimental medicine and biology 40 19928350
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2017 The therapeutic potential of CRTH2/DP2 beyond allergy and asthma. Prostaglandins & other lipid mediators 37 28818625
2010 DP(2) receptor antagonists in development. Expert opinion on investigational drugs 37 20615077
2021 The kinesin KIF1C transports APC-dependent mRNAs to cell protrusions. RNA (New York, N.Y.) 36 34493599
2010 Basophils as APC in Th2 response in allergic inflammation and parasite infection. Current opinion in immunology 36 21095110
2011 Optimization of the Central Core of Indolinone-Acetic Acid-Based CRTH2 (DP2) Receptor Antagonists. ACS medicinal chemistry letters 35 24900359
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2013 COX-1-dependent prostaglandin D2 in microglia contributes to neuropathic pain via DP2 receptor in spinal neurons. Glia 32 23505121
2006 Recombinant HLA-DP2 binds beryllium and tolerizes beryllium-specific pathogenic CD4+ T cells. Journal of immunology (Baltimore, Md. : 1950) 32 16951350
2014 15-deoxy-Δ¹²,¹⁴-PGJ₂ promotes inflammation and apoptosis in cardiomyocytes via the DP2/MAPK/TNFα axis. International journal of cardiology 31 24698234
2011 Antigen-presenting cell (APC) subsets in ovarian cancer. International reviews of immunology 31 21557638
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2001 Adenomatous polyposis coli (APC), beta-catenin, and cadherin are expressed in human bone and cartilage. Histopathology 25 11903580