Premium
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.