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PubMed · 9433138

TCF/LEF factor earn their wings.

H Clevers·M van de Wetering
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Abstract

Factors of the TCF/LEF HMG domain family (TCFs) exist in vertebrates, Drosophila melanogaster and Caenorhabditis elegans. It has very recently become evident that TCFs interact with the vertebrate WNT effector beta-catenin to mediate axis formation in Xenopus. Likewise, Armadillo (the Drosophila ortholog of beta-catenin) is genetically upstream of a Drosophila TCF in the Wingless pathway. Upon Wingless/Wnt signaling, Armadillo/beta-catenin associate with nuclear TCFs and contribute a trans-activation domain to the resulting bipartite transcription factor. The cytoplasmic tumor-suppressor protein APC binds to beta-catenin causing its destruction. In APC-deficient colon carcinoma cells, beta-catenin accumulates and is constitutively complexed with TCF factors. In APC-positive colon carcinomas and melanomas, dominant mutations in beta-catenin render it indestructable, providing an alternative mechanism to activate transcription of TCF target genes inappropriately. So, transcriptional activation of TCF target genes by beta-catenin appears to be a central event in development and cellular transformation.

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AnimalsArmadillo Domain ProteinsBinding SitesColonic NeoplasmsCytoskeletal ProteinsDNA-Binding ProteinsDrosophilaDrosophila ProteinsGene Expression Regulation, DevelopmentalHumansInsect ProteinsLymphoid Enhancer-Binding Factor 1MammalsTrans-ActivatorsTranscription FactorsXenopusXenopus Proteinsbeta CateninJournal ArticleReview

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H Clevers, M van de Wetering. 1997. TCF/LEF factor earn their wings.. https://doi.org/10.1016/s0168-9525(97)01305-x

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