Identification of DNA-dependent protein kinase catalytic subunit as a novel interaction partner of lymphocyte enhancer factor 1

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 tum...

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Veröffentlicht in:Medical molecular morphology 2013-03, Vol.46 (1), p.14-19
Hauptverfasser: Shimomura, Atsushi, Takasaki, Akihiko, Nomura, Ryuji, Hayashi, Nobuhiro, Senda, Takao
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container_end_page 19
container_issue 1
container_start_page 14
container_title Medical molecular morphology
container_volume 46
creator Shimomura, Atsushi
Takasaki, Akihiko
Nomura, Ryuji
Hayashi, Nobuhiro
Senda, Takao
description 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.
doi_str_mv 10.1007/s00795-012-0002-z
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subjects Adenocarcinoma
Adenocarcinoma - metabolism
Anatomy
Biological assays
Catalytic Domain - genetics
Cell Line, Tumor
Colonic Neoplasms - metabolism
Colorectal cancer
Deoxyribonucleic acid
DNA
DNA-Activated Protein Kinase - genetics
DNA-Activated Protein Kinase - metabolism
Fluorescent Antibody Technique
Gene Expression Regulation, Neoplastic - genetics
Glutathione Transferase
Humans
Immunoprecipitation
Kinases
Lymphocytes
Lymphoid Enhancer-Binding Factor 1 - metabolism
Mass Spectrometry
Medicine
Medicine & Public Health
Molecular Medicine
Original Paper
Pathology
Proteins
Wnt Signaling Pathway - genetics
title Identification of DNA-dependent protein kinase catalytic subunit as a novel interaction partner of lymphocyte enhancer factor 1
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