Dazap2 modulates transcription driven by the Wnt effector TCF-4

0333973 - ÚMG 2010 RIV GB eng J - Journal Article
Lukáš, Jan - Mazna, Petr - Valenta, Tomáš - Doubravská, Lenka - Pospíchalová, Vendula - Vojtěchová, Martina - Fafílek, Bohumil - Ivánek, Robert - Plachý, Jiří - Novák, Jakub - Kořínek, Vladimír
Dazap2 modulates transcription driven by the Wnt effector TCF-4.
Nucleic Acids Research. Roč. 37, č. 9 (2009), s. 3007-3020. ISSN 0305-1048. E-ISSN 1362-4962
R&D Projects: GA ČR(CZ) GA204/07/1567; GA MŠMT 2B06077
Institutional research plan: CEZ:AV0Z50520514
Keywords : Wnt signaling * Tcf/Lef transcription factors * Dazap2/Prtb * transcriptional regulation
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 7.479, year: 2009

A typical feature of the transcriptional response induced by Wnt signaling is the involvement of Tcf/Lef factors that function in the nucleus as the principal mediators of signaling. Vertebrate Tcf/Lef proteins perform two well-characterized functions: In association with beta-catenin they activate gene expression, and in the absence of Wnt ligands they act as transcriptional repressors. In this report we reveal that the evolutionary conserved Dazap2 protein functions as a TCF-4 interacting partner. We demonstrate that a short region proximal to the TCF-4 HMG box mediates the interaction and that all Tcf/Lef family members associate with Dazap2. Interestingly, knockdown of Dazap2 not only reduced the activity of Wnt signaling as measured by Tcf/beta-catenin reporters but additionally altered the expression of Wnt signaling target genes. Finally, chromatin immunoprecipitation studies indicate that Dazap2 modulates the affinity of TCF-4 for its DNA recognition motif.
Permanent Link: http://hdl.handle.net/11104/0178824