Clarifying the biological significance of the  CHK 2 K373E somatic mutation discovered in The Cancer Genome Atlas database | Zendy

Higashiguchi Masayoshi | Zendy; Nagatomo Izumi | Zendy; Kijima Takashi | Zendy; Morimura Osamu | Zendy; Miyake Kotaro | Zendy; Minami Toshiyuki | Zendy; Koyama Shohei | Zendy; Hirata Haruhiko | Zendy; Iwahori Kota | Zendy; Takimoto Takayuki | Zendy; Takeda Yoshito | Zendy; Kida Hiroshi | Zendy; Kumanogoh Atsushi | Zendy

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Clarifying the biological significance of the CHK 2 K373E somatic mutation discovered in The Cancer Genome Atlas database

Author(s) -

Higashiguchi Masayoshi,

Nagatomo Izumi,

Kijima Takashi,

Morimura Osamu,

Miyake Kotaro,

Minami Toshiyuki,

Koyama Shohei,

Hirata Haruhiko,

Iwahori Kota,

Takimoto Takayuki,

Takeda Yoshito,

Kida Hiroshi,

Kumanogoh Atsushi

Publication year - 2016

Publication title -

febs letters

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.593

H-Index - 257

eISSN - 1873-3468

pISSN - 0014-5793

DOI - 10.1002/1873-3468.12449

Subject(s) - somatic cell , autophosphorylation , carcinogenesis , mutation , ionizing radiation , biology , database , germline mutation , cancer research , genome , genetics , cancer , kinase , gene , protein kinase a , computer science , physics , irradiation , nuclear physics

We identified CHK 2 K373E as a recurrent mutation in The Cancer Genome Atlas ( TCGA ) database. In this study, we demonstrate that the K373E mutation disrupts CHK 2 autophosphorylation as well as kinase activity, thus leading to impairment of CHK 2 functions in suppressing cell proliferation and promoting cell survival after ionizing radiation. We propose that K373E impairs p53‐independent induction of p21 WAF 1/ CIP 1 by CHK 2. Our data implicate the K373E mutation of CHK 2 in tumorigenesis.

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