NDRG2 acts as a PERK co-factor to facilitate PERK branch and ERS-induced cell death
NDRG2 acts as a PERK co-factor to facilitate PERK branch and ERS-induced cell death
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NDRG2 作为 PERK 辅助因子促进 PERK 分支和 ERS 诱导的细胞死亡
DOI：
10.1002/1873-3468.12861
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发表时间：
2017
期刊：
影响因子：
3.5
通讯作者：
Li Xia
中科院分区：
文献类型：
--
作者：
Zhang Mei;Liu Xiping;Wang Qinhao;Ru Yi;Xiong Xin;Wu Kaichun;Yao Libo;Li Xia
NDRG 2是一种新发现的肿瘤抑制因子，它也对各种应激反应有反应，如缺氧和DNA损伤。在这里，我们报道了在人肝癌SK-Hep-1和HepG 2细胞中，NDRG 2 mRNA和蛋白水平被不同的内质网应激诱导剂（包括Tg，Tm和DTT）上调。此外，使用NDRG 2过表达的肝癌细胞系和Ndrg 2KO小鼠肝脏组织，我们发现，在未折叠蛋白反应信号的三个分支中，NDRG 2通过与蛋白激酶RNA样ER激酶（PERK）相互作用促进PERK途径，增强其下游ATF 4和CHOP。在功能上，NDRG 2部分通过ATF 4或CHOP促进ERS诱导的细胞凋亡。因此，NDRG 2是一种新的ERS应答蛋白，并作为PERK辅因子促进PERK分支，从而促进ERS诱导的细胞凋亡。
NDRG2, a newly identified tumor suppressor, is also responsive to various stresses, such as hypoxia and DNA damage. Here, we reported that in human hepatoma SK‐Hep‐1 and HepG2 cells, NDRG2 mRNA and protein levels were upregulated by different endoplasmic reticulum stress inducers including Tg, Tm, and DTT. Further, using NDRG2‐overexpressing hepatoma cell lines andNdrg2KO mice liver tissues, we found that, among the three branches of unfolded protein response signaling, NDRG2 facilitates protein kinase RNA‐like ER kinase (PERK) pathwayviainteraction with PERK, enhancing its downstream ATF4 and CHOP. Functionally, NDRG2 promotes ERS‐induced apoptosis partially through ATF4 or CHOP. Thus, NDRG2 is a novel ERS‐responsive protein and acts as PERK co‐factor to facilitate PERK branch, thereby contributing to ERS‐induced apoptosis.