APC 3 x 15 beta-catenin-binding domain potentiates beta-catenin association to TBP and upregulates TCF-4 transcriptional activity.
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.
D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D011485:Protein Binding; D035181:TATA-Box Binding Protein / Q000378:metabolism*; D051820:TCF Transcription Factors; D015534:Trans-Activators / Q000378:metabolism*; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; D003598:Cytoskeletal Proteins; D035181:TATA-Box Binding Protein; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D051176:beta Catenin