title: Traf2- and Nck-interacting kinase is essential for canonical Wnt signaling in Xenopus axis formation.
abstract: Wnt signaling pathways play important roles in various stages of developmental events and several aspects of adult homeostasis. Aberrant activation of Wnt signaling has also been associated with several types of cancer. We have recently identified Traf2- and Nck-interacting kinase (TNIK) as a novel activator of Wnt signaling through a comprehensive proteomic approach in human colorectal cancer cell lines. TNIK is an activating kinase for T-cell factor-4 (TCF4) and essential for the beta-catenin-TCF4 transactivation and colorectal cancer growth. Here, we report the essential role of TNIK in Wnt signaling during Xenopus development. We found that Xenopus TNIK (XTNIK) was expressed maternally and that the functional knockdown of XTNIK by catalytically inactive XTNIK (K54R) or antisense morpholino oligonucleotides resulted in significant malformations with a complete loss of head and axis structures. XTNIK enhanced beta-catenin-induced axis duplication and the expression of beta-catenin-TCF target genes, whereas knockdown of XTNIK inhibited it. XTNIK was recruited to the promoter region of beta-catenin-TCF target genes in a beta-catenin-dependent manner. These results demonstrate that XTNIK is an essential factor for the transcriptional activity of the beta-catenin-TCF complex and dorsal axis determination in Xenopus embryos.
authors.affiliation: Chemotherapy Division, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan. resato@ncc.go.jp
authors.forename: Reiko
authors.initials: R
authors.lastname: Satow
authors.forename: Miki
authors.initials: M
authors.lastname: Shitashige
authors.forename: Takafumi
authors.initials: T
authors.lastname: Jigami
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Honda
authors.forename: Masaya
authors.initials: M
authors.lastname: Ono
authors.forename: Setsuo
authors.initials: S
authors.lastname: Hirohashi
authors.forename: Tesshi
authors.initials: T
authors.lastname: Yamada
mesh_terms: D000015:Abnormalities, Multiple / Q000209:etiology; D000818:Animals; D019521:Body Patterning; D004625:Embryo, Nonmammalian; D000081410:Germinal Center Kinases; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic; D051153:Wnt Proteins / Q000378:metabolism*; D014981:Xenopus / Q000196:embryology; D029867:Xenopus Proteins / Q000502:physiology*; D051176:beta Catenin
chemical_list: D000081410:Germinal Center Kinases; C000631453:TNIK protein, Xenopus; D051153:Wnt Proteins; D029867:Xenopus Proteins; D051176:beta Catenin; D017346:Protein Serine-Threonine Kinases; C000631454:TNIK protein, human