Functional characterization of multiple transactivating elements in beta-catenin, some of which interact with the TATA-binding protein in vitro.
beta-Catenin, a member of the family of Armadillo repeat proteins, plays a dual role in cadherin-mediated cell adhesion and in signaling by Wnt growth factors. Upon Wnt stimulation beta-catenin undergoes nuclear translocation and serves as transcriptional coactivator of T cell factor DNA-binding proteins. Previously the transactivation potential of different portions of beta-catenin has been demonstrated, but the precise location of transactivating elements has not been established. Also, the mechanism of transactivation by beta-catenin and the molecular basis for functional differences between beta-catenin and the closely related proteins Armadillo and Plakoglobin are poorly understood. Here we have used a yeast system for the detailed characterization of the transactivation properties of beta-catenin. We show that its transactivation domains possess a modular structure, consist of multiple subelements that cover broad regions at its N and C termini, and extend considerably into the Armadillo repeat region. Compared with beta-catenin the N termini of Plakoglobin and Armadillo have different transactivation capacities that may explain their distinct signaling properties. Furthermore, transactivating elements of beta-catenin interact specifically and directly with the TATA-binding protein in vitro providing further evidence that a major function of beta-catenin during Wnt signaling is to recruit the basal transcription machinery to promoter regions of Wnt target genes.
Hecht
A
A
Max-Planck-Institute of Immunobiology, Stuebeweg 51, D-79108 Freiburg, Germany. hecht@immunbio.mpg.de
Litterst
C M
CM
Huber
O
O
Kemler
R
R
D000818:Animals; D051186:Armadillo Domain Proteins; D015820:Cadherins / Q000378:metabolism; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000235:genetics; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051180:Desmoplakins; D029721:Drosophila Proteins; D017930:Genes, Reporter; D006801:Humans; D019476:Insect Proteins / Q000235:genetics; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D015398:Signal Transduction; D035181:TATA-Box Binding Protein; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D051185:gamma Catenin; D000095002:Delta Catenin
D051186:Armadillo Domain Proteins; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051180:Desmoplakins; D029721:Drosophila Proteins; D019476:Insect Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D035181:TATA-Box Binding Protein; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D051185:gamma Catenin; D000095002:Delta Catenin