title: Clarifying the biological significance of the CHK2 K373E somatic mutation discovered in The Cancer Genome Atlas database.
abstract: We identified CHK2 K373E as a recurrent mutation in The Cancer Genome Atlas (TCGA) database. In this study, we demonstrate that the K373E mutation disrupts CHK2 autophosphorylation as well as kinase activity, thus leading to impairment of CHK2 functions in suppressing cell proliferation and promoting cell survival after ionizing radiation. We propose that K373E impairs p53-independent induction of p21WAF1/CIP1by CHK2. Our data implicate the K373E mutation of CHK2 in tumorigenesis.
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Higashiguchi
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Nagatomo
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Japan.|Department of Immunopathology, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kijima
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Morimura
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Miyake
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Minami
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Koyama
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Hirata
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Iwahori
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Takimoto
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Takeda
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kida
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Japan.|Department of Immunopathology, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Japan.|AMED-CREST, Osaka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumanogoh
mesh_terms: D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D064447:Checkpoint Kinase 2 / Q000235:genetics* / Q000378:metabolism; D030541:Databases, Genetic; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation
chemical_list: D064447:Checkpoint Kinase 2
keywords: The Cancer Genome Atlas; cancer genome; checkpoint kinase 2; p21WAF1/CIP1; somatic mutation