Zhang Mei, Liu Xiping, Wang Qinhao, Ru Yi, Xiong Xin, Wu Kaichun, Yao Libo, Li Xia
State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an, China.
Department of Biochemistry and Molecular Biology, Zunyi Medical College, China.
FEBS Lett. 2017 Nov;591(21):3670-3681. doi: 10.1002/1873-3468.12861. Epub 2017 Oct 15.
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 and Ndrg2KO mice liver tissues, we found that, among the three branches of unfolded protein response signaling, NDRG2 facilitates protein kinase RNA-like ER kinase (PERK) pathway via interaction 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.
