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Adenomatous polyposis coli (APC) mutations cause Wnt pathway activation in human cancers. Current models for APC action emphasize its role in promoting β-catenin degradation downstream of Wnt receptors. Unexpectedly, we find that blocking Wnt receptor activity in APC-deficient cells inhibits Wnt signaling independently of Wnt ligand. We also show that inducible loss of APC is rapidly followed by Wnt receptor activation and increased β-catenin levels. In contrast, APC2 loss does not promote receptor activation. We show that APC exists in a complex with clathrin and that Wnt pathway activation in APC-deficient cells requires clathrin-mediated endocytosis. Finally, we demonstrate conservation of this mechanism in Drosophila intestinal stem cells. We propose a model in which APC and APC2 function to promote β-catenin degradation, and APC also acts as a molecular "gatekeeper" to block receptor activation via the clathrin pathway.
Pubmed ID: 29533772 RIS Download
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An independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.
View all literature mentionsCollects, maintains and distributes Drosophila melanogaster strains for research. Emphasis is placed on genetic tools that are useful to a broad range of investigations. These include basic stocks of flies used in genetic analysis such as marker, balancer, mapping, and transposon-tagging strains; mutant alleles of identified genes, including a large set of transposable element insertion alleles; defined sets of deficiencies and a variety of other chromosomal aberrations; engineered lines for somatic and germline clonal analysis; GAL4 and UAS lines for targeted gene expression; enhancer trap and lacZ-reporter strains with defined expression patterns for marking tissues; and a collection of transposon-induced lethal mutations.
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis unknown targets Chicken IgG (H+L)
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis recombinant polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsThis isotype control targets Not Applicable
View all literature mentionsThis unknown targets mouse-IgG-control
View all literature mentionsThis unknown targets normal rabbit IgG
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis monoclonal targets Prospero protein
View all literature mentionsThis monoclonal targets Mouse Drosophila Armadillo Protein
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis polyclonal targets Human APC2
View all literature mentionsThis polyclonal targets Axin-1, aa 210-410
View all literature mentionsThis polyclonal targets Giantin - Golgi Marker
View all literature mentionsThis polyclonal targets phospho LRP-6 (Thr1572)
View all literature mentionsThis monoclonal targets Clathrin Heavy Chain
View all literature mentionsThis monoclonal targets Clathrin Heavy Chain (D3C6) XP Rabbit mAb
View all literature mentionsThis monoclonal targets RSV-CEF Caveolin aa. 1-178
View all literature mentionsThis polyclonal targets Caveolin
View all literature mentionsThis monoclonal targets LRP6 (C47E12) Rabbit mAb
View all literature mentionsThis monoclonal targets LRP5 (D80F2) Rabbit mAb
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsSoftware package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01253}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC05546}attP40 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HMC03571}attP40 from BDSC.
View all literature mentionsMus musculus with name C57BL/6J-ApcMin/J from IMSR.
View all literature mentionsCell line 3T3 MEFs KO is a Spontaneously immortalized cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line L-M(TK-) is a Spontaneously immortalized cell line with a species of origin Mus musculus
View all literature mentionsCell line L Wnt-3A is a Spontaneously immortalized cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line DLD-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line RKO is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
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