TCF/LEF factor earn their wings.
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.
Clevers
H
H
Department of Immunology, University Hospital Utrecht, The Netherlands. h.clevers@lab.azu.nl
van de Wetering
M
M
D000818:Animals; D051186:Armadillo Domain Proteins; D001665:Binding Sites; D003110:Colonic Neoplasms / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D004330:Drosophila / Q000235:genetics / Q000254:growth & development; D029721:Drosophila Proteins; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D051821:Lymphoid Enhancer-Binding Factor 1; D008322:Mammals / Q000254:growth & development; D015534:Trans-Activators; D014157:Transcription Factors / Q000737:chemistry / Q000502:physiology*; D014981:Xenopus / Q000235:genetics / Q000254:growth & development; D029867:Xenopus Proteins; D051176:beta Catenin
C495305:ARM protein, Drosophila; D051186:Armadillo Domain Proteins; C495266:CTNNB1 protein, Xenopus; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; D051176:beta Catenin