You Jin, Wang Xingshun, Wang Jiuling, Yuan Baolei, Zhang Yandong
Department of Biology, Southern University of Science and Technology , Shenzhen, Guangdong, China.
Cell Death Discov. 2017 Jan 9;3:16095. doi: 10.1038/cddiscovery.2016.95. eCollection 2017.
DEAD box proteins are multifunctional proteins involved in every aspect in RNA metabolism and have essential roles in many cellular activities. Despite their importance, many DEAD box proteins remain uncharacterized. In this report, we found DDX59 overexpressed in lung adenocarcinoma. DDX59 knockdown reduced cell proliferation, anchorage-independent cell growth, and caused reduction of tumor formation in immunocompromised mice. In multiple lung cancer cells, we found that DDX59 knockdown inhibits DNA synthesis; wild-type DDX59 but not helicase-defective mutant of DDX59 enhances DNA synthesis. DDX59 knockdown caused reduction of MCM protein levels, decreased the loading of MCM ring protein onto chromatin, and therefore inhibited DNA replication. Our study reveals for the first time that DDX59 has an important role in lung cancer development through promoting DNA replication.
DEAD盒蛋白是多功能蛋白,参与RNA代谢的各个方面,在许多细胞活动中发挥着重要作用。尽管它们很重要,但许多DEAD盒蛋白仍未被鉴定。在本报告中,我们发现DDX59在肺腺癌中过表达。敲低DDX59可减少细胞增殖、非锚定依赖性细胞生长,并导致免疫缺陷小鼠肿瘤形成减少。在多个肺癌细胞中,我们发现敲低DDX59可抑制DNA合成;野生型DDX59而非DDX59解旋酶缺陷型突变体可增强DNA合成。敲低DDX59导致MCM蛋白水平降低,减少MCM环蛋白在染色质上的装载,从而抑制DNA复制。我们的研究首次揭示DDX59通过促进DNA复制在肺癌发生发展中起重要作用。