Integrated stress response of vertebrates is regulated by four eIF2α kinases.
Integrated stress response of vertebrates is regulated by four eIF2α kinases.
复制标题
DOI：
10.1038/srep32886
复制
发表时间：
2016-09-16
影响因子：
4.6
通讯作者：
Oyadomari S
中科院分区：
文献类型：
--
作者：
Taniuchi S;Miyake M;Tsugawa K;Oyadomari M;Oyadomari S
综合应激反应（integrated stress response， ISR）是一种由真核翻译起始因子2 （eIF2α）残基丝氨酸-51磷酸化启动的细胞保护途径，它对各种应激条件下的翻译控制至关重要。到目前为止，已经确定了四种eIF2α激酶，即血红素调节抑制剂（HRI）、蛋白激酶R （PKR）、激酶样内质网激酶（PERK）和一般控制非抑制性2 (GCN2)，它们分别被血红素耗尽、病毒感染、内质网应激和氨基酸饥饿激活。由于eIF2α在各种应激条件下被磷酸化，因此存在额外的eIF2α激酶。为了验证未知eIF2α激酶的存在，我们构建了eIF2α激酶四重敲除细胞（4KO细胞），其中使用CRISPR/ cas9介导的基因组编辑删除了四个已知的eIF2α激酶基因。在各种应激刺激下，4KO细胞中eIF2α的磷酸化被完全消除。我们的数据表明，已知的四种eIF2α激酶对于ISR是足够的，并且在脊椎动物中没有额外的eIF2α激酶。
The integrated stress response (ISR) is a cytoprotective pathway initiated upon phosphorylation of the eukaryotic translation initiation factor 2 (eIF2α) residue designated serine-51, which is critical for translational control in response to various stress conditions. Four eIF2α kinases, namely heme-regulated inhibitor (HRI), protein kinase R (PKR), PKR-like endoplasmic reticulum kinase, (PERK) and general control non-depressible 2 (GCN2), have been identified thus far, and they are known to be activated by heme depletion, viral infection, endoplasmic reticulum stress, and amino acid starvation, respectively. Because eIF2α is phosphorylated under various stress conditions, the existence of an additional eIF2α kinase has been suggested. To validate the existence of the unidentified eIF2α kinase, we constructed an eIF2α kinase quadruple knockout cells (4KO cells) in which the four known eIF2α kinase genes were deleted using the CRISPR/Cas9-mediated genome editing. Phosphorylation of eIF2α was completely abolished in the 4KO cells by various stress stimulations. Our data suggests that the four known eIF2α kinases are sufficient for ISR and that there are no additional eIF2α kinases in vertebrates.
登录
查看更多内容
影响因子：
4.1
作者：
Gomez, Edith;Powell, Mike L.;Herbert, Terence P.
通讯作者：
Herbert, Terence P.
影响因子：
64.8
作者：
Costa-Mattioli, M;Gobert, D;Sonenberg, N
通讯作者：
Sonenberg, N
影响因子：
9.2
作者：
Deng, J;Harding, HP;Sonenberg, N
通讯作者：
Sonenberg, N
GCN2样EIF2α激酶管理弓形虫弓形虫中的氨基酸饥饿反应。
影响因子：
4
作者：
Konrad, Christian;Wek, Ronald C.;Sullivan, William J., Jr.
通讯作者：
Sullivan, William J., Jr.
影响因子：
64.5
作者：
MEURS, E;CHONG, K;HOVANESSIAN, AG
通讯作者：
HOVANESSIAN, AG