title: Identification of DNA-dependent protein kinase catalytic subunit as a novel interaction partner of lymphocyte enhancer factor 1.
abstract: Lymphocyte enhancer factor 1 (LEF1), a member of the LEF/T-cell-specific factor (TCF) family of the high mobility group domain transcription factors, acts downstream in canonical Wnt signaling. Aberrant transactivation of LEF1 contributes to the tumorigenesis of colonic neoplasms, sebaceous skin tumors, and lymphoblastic leukemia. LEF1-associated proteins are crucial for regulating its transcriptional activity. In this study, glutathione-S-transferase pull-down assay and mass spectrometry enabled identification of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) as a novel interaction partner for LEF1. The interaction between LEF1 and DNA-PKcs was confirmed using in vivo co-immunoprecipitation. Furthermore, double immunofluorescence observations showed that LEF1 and DNA-PKcs colocalized in the nuclei of colon adenocarcinoma cell lines. Identification of the interaction between LEF1 and DNA-PKcs may provide clues for a novel therapy for cancer treatment as well as for understanding LEF1-mediated transcriptional regulation.
authors: Department of Anatomy I, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, Japan. shimo@fujita-hu.ac.jp
authors: Atsushi
authors: A
authors: Shimomura
authors: Akihiko
authors: A
authors: Takasaki
authors: Ryuji
authors: R
authors: Nomura
authors: Nobuhiro
authors: N
authors: Hayashi
authors: Takao
authors: T
authors: Senda
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D020134:Catalytic Domain / Q000235:genetics; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism*; D051747:DNA-Activated Protein Kinase / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005982:Glutathione Transferase; D006801:Humans; D047468:Immunoprecipitation; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism*; D013058:Mass Spectrometry; D060449:Wnt Signaling Pathway / Q000235:genetics*
chemical_list: C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; D005982:Glutathione Transferase; D051747:DNA-Activated Protein Kinase