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All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAcgRkqy_g8S-tzYZg-RfIqqwSm9lZY1Z4Hqdy1nEX7QU#_8 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RAcgRkqy_g8S-tzYZg-RfIqqwSm9lZY1Z4Hqdy1nEX7QU#_7 http://www.w3.org/ns/prov#value Wnt signaling is bypassed in many melanoma cell lines owing to mutations in beta catenin which result in its stabilization. Although deregulation of Wnt- and RTK-mediated signaling will affect a range of target genes, both pathways impact on Mitf expression or Mitf levels. Note also that while GSK3beta is regulated by both RTK signaling and the Wnt signaling pathway, it is likely that each pathway regulates a different pool of GSK3beta The presence of a Wnt ligand activates the receptor for Wnt, the seven transmembrane domain protein Frizzled, which in turn leads to activation of Dishevelled, and subsequently to the inhibition of GSK-3. Current models suggest that the action of GSK-3 results in phosphorylation of beta catenin leading to its destabilization and degradation (Cadigan and Nusse 1997) and as a consequence, the presence of a Wnt signal increases the level of beta catenin in the cell. Control of beta catenin degradation is also influenced by components of a complex containing the product of the adenomatous polyposis coli gene APC, which is a good substrate for GSK3beta in vitro and which can form a complex with GSK3beta and beta catenin, together with the axin homolog conductin (Rubinfeld et al. 1993, 1996; Behrens et al. 1998). Indeed, phosphorylation of APC by GSK3beta stimulates its ability to bind beta catenin and overexpression of APC following transfection substantially reduces beta catenin levels (Munemitsu et al. 1995). Similarly, overexpression of conductin also results in degradation of beta catenin and it has been suggested that conductin acts downstream from APC in directing the destabilization of beta catenin containing the product of the adenomatous polyposis coli gene APC, which is a good substrate for GSK3beta in vitro and which can form a complex with GSK3beta and beta catenin, together with the axin homolog conductin (Rubinfeld et al. 1993, 1996; Behrens et al. 1998). Indeed, phosphorylation of APC by GSK3beta stimulates its ability to bind beta catenin and overexpression of APC following transfection substantially reduces beta catenin levels (Munemitsu et al. 1995). Similarly, overexpression of conductin also results in degradation of beta catenin and it has been suggested that conductin acts downstream from APC in directing the destabilization of beta catenin Lef1 in the absence of a Wnt signal can repress transcription in association with Groucho-like factors. Similarly, under some circumstances Pax3 can repress transcription, perhaps through its interaction with HIRA (Magnaghi et al. 1998), amammalian homolog of a yeast transcriptional corepressor, and with the transcriptional repressor hDaxx which can suppress the ability of Pax3 to activate transcription http://www.tkuhn.ch/bel2nanopub/RAcgRkqy_g8S-tzYZg-RfIqqwSm9lZY1Z4Hqdy1nEX7QU#_7 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/10898786 http://www.tkuhn.ch/bel2nanopub/RAcgRkqy_g8S-tzYZg-RfIqqwSm9lZY1Z4Hqdy1nEX7QU#_8 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAcgRkqy_g8S-tzYZg-RfIqqwSm9lZY1Z4Hqdy1nEX7QU#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/10898786 http://www.tkuhn.ch/bel2nanopub/RAcgRkqy_g8S-tzYZg-RfIqqwSm9lZY1Z4Hqdy1nEX7QU#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAcgRkqy_g8S-tzYZg-RfIqqwSm9lZY1Z4Hqdy1nEX7QU#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAcgRkqy_g8S-tzYZg-RfIqqwSm9lZY1Z4Hqdy1nEX7QU#_7 http://www.tkuhn.ch/bel2nanopub/RAcgRkqy_g8S-tzYZg-RfIqqwSm9lZY1Z4Hqdy1nEX7QU#pubinfo http://www.tkuhn.ch/bel2nanopub/RAcgRkqy_g8S-tzYZg-RfIqqwSm9lZY1Z4Hqdy1nEX7QU http://purl.org/dc/terms/created 2014-07-03T14:29:51.675+02:00 http://www.tkuhn.ch/bel2nanopub/RAcgRkqy_g8S-tzYZg-RfIqqwSm9lZY1Z4Hqdy1nEX7QU http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAcgRkqy_g8S-tzYZg-RfIqqwSm9lZY1Z4Hqdy1nEX7QU http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234