1. APC 3×15 β-catenin-binding domain potentiates β-catenin association to TBP and upregulates TCF-4 transcriptional activity
- Author
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Daniel Martínez, Jose Piedra, Antonio García de Herreros, Santiago Roura, Mireia Duñach, and Susana Miravet
- Subjects
Beta-catenin ,Transcription, Genetic ,Adenomatous polyposis coli ,Adenomatous Polyposis Coli Protein ,Biophysics ,Plasma protein binding ,Biology ,Transfection ,TCF/LEF family ,Biochemistry ,APC/C activator protein CDH1 ,Adherens junction ,Molecular Biology ,beta Catenin ,Cell Biology ,TATA-Box Binding Protein ,Molecular biology ,Up-Regulation ,Cytoskeletal Proteins ,Catenin ,Trans-Activators ,biology.protein ,TCF Transcription Factors ,Transcription Factor 7-Like 2 Protein ,Protein Binding ,Transcription Factors ,Binding domain - Abstract
Beta-catenin plays a dual role as a regulatory component of adherens junctions and as a transcriptional cofactor. The nuclear activity of this protein is controlled by adenomatous polyposis coli (APC) protein. We have analyzed the effect on beta-catenin-dependent transcription of a beta-catenin binding domain present in APC, consisting in three 15-amino acid repeats (APC 3 x 15). Association of this fragment prevents the interaction of beta-catenin with E-cadherin but not with TCF-4. Transfection of this fragment to several cell lines increases the transcriptional activity of the beta-catenin-TCF-4 complex and promotes the translocation of beta-catenin to the nucleus. Moreover, previous binding of APC 3 x 15 facilitates the association of beta-catenin to the TATA box-associated protein. Therefore, APC 3 x 15 domain plays a positive role in the control of transcriptional activity of beta-catenin-TCF-4 and can contribute to explain the role of the truncated forms of APC in colon tumorigenesis.
- Published
- 2003
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