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
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DOI：
10.1002/1873-3468.12449
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发表时间：
2016-12-01
期刊：
影响因子：
3.5
通讯作者：
Kumanogoh, Atsushi
中科院分区：
文献类型：
--
作者：
Higashiguchi, Masayoshi;Nagatomo, Izumi;Kumanogoh, Atsushi
我们在癌症基因组图谱（TCGA）数据库中将CHK 2 K373 E鉴定为复发性突变。在这项研究中，我们证明了K373 E突变破坏CHK 2自磷酸化以及激酶活性，从而导致CHK 2在电离辐射后抑制细胞增殖和促进细胞存活方面的功能受损。我们提出K373 E损害CHK 2对p21（WAF 1/CIP 1）的p53非依赖性诱导。我们的数据暗示CHK 2的K373 E突变在肿瘤发生中。
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 p21(WAF1/CIP1) by CHK2. Our data implicate the K373E mutation of CHK2 in tumorigenesis.