Journal ArticleDOI
Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC−/− Colon Carcinoma
Vladimir Korinek,Nick Barker,Patrice J. Morin,Dick F. van Wichen,Roel A. de Weger,Kenneth W. Kinzler,Bert Vogelstein,Hans Clevers +7 more
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TLDR
Constitutive transcription of Tcf target genes, caused by loss of APC function, may be a crucial event in the early transformation of colonic epithelium.Abstract:
The adenomatous polyposis coli (APC) tumor suppressor protein binds to beta-catenin, a protein recently shown to interact with Tcf and Lef transcription factors. The gene encoding hTcf-4, a Tcf family member that is expressed in colonic epithelium, was cloned and characterized. hTcf-4 transactivates transcription only when associated with beta-catenin. Nuclei of APC-/- colon carcinoma cells were found to contain a stable beta-catenin-hTcf-4 complex that was constitutively active, as measured by transcription of a Tcf reporter gene. Reintroduction of APC removed beta-catenin from hTcf-4 and abrogated the transcriptional transactivation. Constitutive transcription of Tcf target genes, caused by loss of APC function, may be a crucial event in the early transformation of colonic epithelium.read more
Citations
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The Ubiquitin System
Avram Hershko,Aaron Ciechanover +1 more
TL;DR: This review discusses recent information on functions and mechanisms of the ubiquitin system and focuses on what the authors know, and would like to know, about the mode of action of ubi...
Journal ArticleDOI
Wnt/beta-catenin signaling in development and disease.
TL;DR: A remarkable interdisciplinary effort has unraveled the WNT (Wingless and INT-1) signal transduction cascade over the last two decades, finding that Germline mutations in the Wnt pathway cause several hereditary diseases, and somatic mutations are associated with cancer of the intestine and a variety of other tissues.
Journal ArticleDOI
Wnt/β-catenin signaling: components, mechanisms, and diseases
TL;DR: Some key aspects of Wnt/beta-catenin signaling in human diseases including congenital malformations, cancer, and osteoporosis are highlighted, and potential therapeutic implications are discussed.
Journal ArticleDOI
Identification of c-MYC as a Target of the APC Pathway
Tong-Chuan He,Andrew B. Sparks,Carlo Rago,Heiko Hermeking,Leigh Zawel,Luis T. da Costa,Patrice J. Morin,Bert Vogelstein,Kenneth W. Kinzler +8 more
TL;DR: The c-MYC oncogene is identified as a target gene in this signaling pathway and shown to be repressed by wild-type APC and activated by beta-catenin, and these effects were mediated through Tcf-4 binding sites in the c- MYC promoter.
Journal ArticleDOI
Wnt/β-catenin signaling and disease.
Hans Clevers,Roel Nusse +1 more
TL;DR: An update of the core Wnt/β-catenin signaling pathway is provided, how its various components contribute to disease, and outstanding questions to be addressed in the future are discussed.
References
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Journal ArticleDOI
Lessons from Hereditary Colorectal Cancer
TL;DR: The authors are grateful to the members of their laboratories for their contributions to the reviewed studies and to F. Giardiello and S. Hamilton for photographs of colorectal lesions.
Journal ArticleDOI
Functional interaction of beta-catenin with the transcription factor LEF-1.
Jürgen Behrens,von Kries Jp,Michael Kühl,Bruhn L,Bruhn L,Doris Wedlich,Rudolf Grosschedl,Rudolf Grosschedl,Walter Birchmeier +8 more
TL;DR: β-catenin regulates gene expression by direct interaction with transcription factors such as LEF-1, providing a molecular mechanism for the transmission of signals from cell-adhesion components or wnt protein to the nucleus.
Journal ArticleDOI
XTcf-3 Transcription Factor Mediates β-Catenin-Induced Axis Formation in Xenopus Embryos
Miranda Molenaar,Marc van de Wetering,Mariëtte A. Oosterwegel,Josi Peterson-Maduro,Susan Godsave,Vladimir Korinek,Jeroen P. Roose,Olivier Destrée,Hans Clevers +8 more
TL;DR: It is proposed that signaling by beta-catenin involves complex formation with XT cf-3, followed by nuclear translocation and activation of specific XTcf-3 target genes, which suppresses endogenous axis specification upon injection into the dorsal blastomeres of a 4-cell-stage embryo.
Journal ArticleDOI
Binding of GSK3β to the APC-β-Catenin Complex and Regulation of Complex Assembly
TL;DR: It is shown that when β-catenin is present in excess, APC binds to another component of the WINGLESS pathway, glycogen synthase kinase 3β (GSK3β), a mammalian homolog of Drosophila ZESTE WHITE 3, which was a good substrate for GSK3β in vitro and the phosphorylation sites were mapped to the central region of APC.
Journal ArticleDOI
Association of the APC gene product with beta-catenin
Bonnee Rubinfeld,Brian Souza,Iris Albert,Oliver Müller,Scott H. Chamberlain,Frank R. Masiarz,Susan Munemitsu,Paul G. Polakis +7 more
TL;DR: Results suggest that APC is involved in cell adhesion, and an antibody specific to beta-catenin also recognized the 95-kilodalton protein in the immunoprecipitates.