• mutation
  • Refining the relation between 'first hits' and 'second hits' at the APC locus: the 'loose fit' model and evidence for differences in somatic mutation spectra among patients. (herbalpalace.com)
  • In pedigrees without identified APC gene mutation, analysis of linkage to chromosome 5q and/or assessment of neoplasms for replication errors characteristic of mutation in mismatch repair genes were performed. (bmj.com)
  • In patients without identified APC gene mutation, linkage to the APC gene was found in one large family (lod = 5.1, theta 0.01), and replication error phenotype was absent in all 24 neoplasms from 16 members of these nine pedigrees. (bmj.com)
  • CONCLUSIONS: Patients with the colorectal phenotype of FAP but no extraintestinal manifestations may have non-truncating mutations of the APC gene or mutation in a gene other than APC or mismatch repair genes. (bmj.com)
  • The site of APC gene mutation is associated with pigmented ocular fundus lesions (codons 542-1309) and predisposition to multiplicity of extraintestinal manifestations (codons 1465, 1546, and 2621). (bmj.com)
  • 1994) A targeted chain-termination mutation in the mouse Apc gene results in multiple intestinal tumors. (springer.com)
  • binds
  • APC bound to EPCR activates the protease activated receptor-1 (PAR-1) which binds the G q and G i proteins to activate phosophlipase(s) (PLC) in SMCs and endothelium resulting in IP3 (inositol triphosphate)-mediated release of intracellular [Ca 2+ ] i , activation of mitogen-activated kinases ERK1/2 and stimulation of DNA synthesis. (ahajournals.org)
  • Soluble form of EPCR (sEPCR) binds APC/PC and forms complexes with proteinase-3 (PR3) which binds to Mac-1 on leukocytes and activates antiinflammatory signaling. (ahajournals.org)
  • 15 Proteinase-3 (PR3), a serine protease with elastase-like properties stored in granules of neutrophils, binds both Mac-1 and soluble EPCR which may be implicated in APC mediated signaling and activation of PC on leukocytes, because soluble EPCR:PR3 complexes bind both APC and PC. (ahajournals.org)
  • The APC binds to β-catenin, axin and glycogen synthase kinase 3β to form a large protein complex, in which β-catenin is phosphorylated and broken down, resulting in negative regulation of the Wnt signaling pathway. (springer.com)
  • Through its C-terminus, APC binds to post-synaptic density discs large zonula occludens domain-containing proteins, such as discs large (DLG) and post-synaptic density (PSD)-95, and may play important roles in epithelial morphogenesis, brain development and neuronal functions. (springer.com)
  • protein
  • 1 EPCR was isolated and cloned as an endothelial cell-specific, high selectivity and high affinity binding protein for protein C (PC) and activated PC (APC). (ahajournals.org)
  • 2 The APC anticoagulant pathway is mediated by proteolytic inactivation of blood coagulation Factors Va and VIIIa with the contribution of several cofactors, including protein S, high density lipoproteins, phosphatidylserine, cardiolipin, and glucosylceramide to name a few. (ahajournals.org)
  • Consistent with the idea that such dominant effects are normally balanced by interactions within the full-length molecule, protein interactions of N-terminal fragments expressed in tumour cells can be altered by binding to C-terminal regions of APC commonly lost in tumours. (biochemsoctrans.org)
  • The Apc gene product (APC), basically a cytoplasmic protein, blocks cell cycle progression and plays crucial roles in development. (springer.com)
  • αE-catenin, also known as Catenin alpha-1 is a protein that in humans is encoded by the CTNNA1 gene. (wikipedia.org)
  • GSK3
  • APC facilitates phosphorylation of β-catenin by GSK3β and targeting of β-catenin for ubiquitin-mediated degradation. (biologists.org)
  • intracellular
  • 22 The data show that EPCR mediates APC signaling in SMCs, resulting in increases in intracellular [Ca 2+ ] i , phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK-1/2) and DNA synthesis ( Figure 1 ). (ahajournals.org)
  • nucleus
  • EPCR translocates itself from the plasma membrane to the nucleus and may internalize APC into injured vascular cells, but the physiological importance of EPCR internalization alone and/or of its ligands remains at present elusive. (ahajournals.org)
  • The APC, having some nuclear localizing signals in its molecule, can also be localized in the nucleus. (springer.com)
  • pathway
  • The APC cellular pathway on endothelium requires EPCR and the protease activated receptor-1 (PAR-1) 3 which mediates APC's cytoprotective effects, including alterations in gene expression profiles, antiapoptotic activity, antiinflammatory activity and protection of endothelial barriers 4-10 ( Figure 1 ). (ahajournals.org)
  • 22 In injured endothelium, EPCR-APC-mediated PAR-1 activation blocks mitochondria-mediated apoptotic pathway (eg, inhibition of p53 and Bax, activation of antiapoptotic Bcl-2 gene, blockade of caspase-9), and death receptor-mediated pathway through inhibition of caspase-8. (ahajournals.org)
  • 1998) Identification of c-MYC as a target of the APC pathway. (springer.com)
  • membrane
  • Structural and functional characterization of the Wnt inhibitor APC membrane recruitment 1 (Amer1). (xenbase.org)
  • differentiation
  • The high penetrance of APC mutations, especially in gut epithelium, supports the idea that APC may be involved in a number of the processes that govern the normal maintenance of this tissue: differentiation, migration, proliferation and apoptosis. (biochemsoctrans.org)
  • deletion
  • To investigate the functional role of Apc in the central nervous system, we analyzed the neurological phenotypes of Apc 1638T/1638T mice, which carry a targeted deletion of the 3′ terminal third of Apc that does not affect Wnt signaling. (biomedcentral.com)
  • nuclear
  • EPCR-APC-dependent PAR-1 activation in leukocytes and endothelium blocks the expression of proinflammatory genes by preventing nuclear translocation of nuclear factor-κB (NF-κB). (ahajournals.org)
  • The nuclear APC exports excess β-catenin to the cytoplasm. (springer.com)
  • RESULTS
  • Our results demonstrate that the C-terminus of the Apc tumor suppressor plays a critical role in cognitive and neuropsychiatric functioning. (biomedcentral.com)
  • These results indicate that APC is involved in both early neurite outgrowth and increased growth of the future axon, and that β-catenin has a structural role in inhibiting APC function in neurite growth. (biologists.org)
  • target
  • Knockdown of Amer1 leads to the activation of Wnt target genes, preferentially in dense compared with sparse cell cultures, suggesting that Amer1 function is regulated by cell contacts. (xenbase.org)
  • Cell
  • In addition, N-terminal fragments of APC, like those commonly found in tumours, compromise cell migration in Dictyostelium and in early developing chicken embryos. (biochemsoctrans.org)
  • 1995) The tumour suppressor gene product APC blocks cell cycle progression from G0/G1 to S phase. (springer.com)
  • found
  • Recently, we found that APC is required for the activity of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors by facilitating the clustering of PSD-95 and these receptors at the postsynapse. (springer.com)
  • patients
  • METHODS: Mutations of the APC gene were compared with the occurrence of seven extraintestinal manifestations in 475 FAP patients from 51 families. (bmj.com)
  • However, except for the observed low penetrance of medulloblastoma among patients with FAP [ 3 ], APC mutations do not seem to be associated with brain tumorigenesis. (biomedcentral.com)
  • forms
  • Activated PC (APC) dissociates from EPCR and TM-thrombin complexes and inactivates coagulation factors Va and VIIIa into inactive forms V i and VIII i promoting anticoagulation. (ahajournals.org)