title: DKK1, a negative regulator of Wnt signaling, is a target of the beta-catenin/TCF pathway.
abstract: Wnt signaling plays an important role in embryonic development and tumorigenesis. These biological effects are exerted by activation of the beta-catenin/TCF transcription complex and consequent regulation of a set of downstream genes. TCF-binding elements have been found in the promoter regions of many TCF target genes and characterized by a highly conserved consensus sequence. Utilizing this consensus sequence, we performed an in silico screening for new TCF target genes. Through computational screening and subsequent experimental analysis, we identified a novel TCF target gene, DKK1, which has been shown to be a potent inhibitor of Wnt signaling. Our finding suggests the existence of a novel feedback loop in Wnt signaling.
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Niida
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Hiroko
authors.forename: Mana
authors.initials: M
authors.lastname: Kasai
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Furukawa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Sumio
authors.initials: S
authors.lastname: Sugano
authors.forename: Tetsu
authors.initials: T
authors.lastname: Akiyama
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019295:Computational Biology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism; D025461:Feedback, Physiological / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D051153:Wnt Proteins; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; C501126:DKK1 protein, human; C501127:Dkk1 protein, mouse; D029721:Drosophila Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; C115159:pan protein, Drosophila