- Clarifying the biological significance of the CHK2 K373E somatic mutation discovered in The Cancer Genome Atlas database.
Clarifying the biological significance of the CHK2 K373E somatic mutation discovered in The Cancer Genome Atlas database.
FEBS letters (2016-10-26)
Masayoshi Higashiguchi, Izumi Nagatomo, Takashi Kijima, Osamu Morimura, Kotaro Miyake, Toshiyuki Minami, Shohei Koyama, Haruhiko Hirata, Kota Iwahori, Takayuki Takimoto, Yoshito Takeda, Hiroshi Kida, Atsushi Kumanogoh
PMID27716909
摘要
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/CIP1 by CHK2. Our data implicate the K373E mutation of CHK2 in tumorigenesis.