RIG1 suppresses Ras activation and induces cellular apoptosis at the Golgi apparatus
RIG1 suppresses Ras activation and induces cellular apoptosis at the Golgi apparatus
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DOI：
10.1016/j.cellsig.2006.11.005
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发表时间：
2007-05-01
影响因子：
4.8
通讯作者：
Jiang, Shun-Yuan
中科院分区：
文献类型：
--
作者：
Tsai, Fu-Ming;Shyu, Rong-Yaun;Jiang, Shun-Yuan
RIG I是一种生长调节因子，通过抑制RAS的活化来抑制RAS/丝裂原活化蛋白激酶途径。共聚焦显微镜分析表明，RIG 1定位于内质网（ER）和高尔基体在HtTA宫颈癌细胞。构建并验证了靶向高尔基体或ER的羧基末端缺失的RIG 1。在与野生型或高尔基体靶向的RIG 1共转染的细胞中，HRAS的激活分别被抑制25.1%或81.4%。野生型或高尔基体靶向RIG I表达24小时诱导HtTA细胞的细胞凋亡，如通过MTT测定、乳酸脱氢酶释放和染色质凝聚所评估的。相反，ER靶向的RIG 1和羧基末端缺失的RIG 1（RIG 1 Delta C）没有表现出活性。在野生型和高尔基体靶向的RIG表达后，半胱天冬酶-2、-3和-9被激活]。尽管半胱天冬酶-3抑制剂Z-DEVD-FMK部分或完全逆转了野生型或高尔基体靶向的RIG 1诱导的细胞死亡，但它并不能阻止RIG 1的抗RAS作用。总之，RIG I的促凋亡和抗RAS活性主要与蛋白质的高尔基体定位相关。RIG I的促凋亡活性是通过激活caspase-2和-3介导的，并且不依赖于其对RAS的作用。(c)2006年爱思唯尔公司All rights reserved.
Retinoid-inducible gene I encodes RIG I is a growth regulator, which inhibits the pathways of the RAS/mitogen-activated protein kinases by suppressing the activation of RAS. Confocal microscopic analysis demonstrated that RIG1 is localized in the endoplasmic reticulum (ER) and Golgi apparatus in HtTA cervical cancer cells. Carboxyterminal-deleted RIG1 targeted to the Golgi or ER was constructed and validated. The activation of HRAS was inhibited by 25.1% or 81.4% in cells cotransfected with wild-type or Golgi-targeted RIG 1, respectively. Expression of wild-type or Golgi-targeted RIG I for 24 h induced cellular apoptosis in HtTA cells, as assessed by MTT assay, the release of lactate dehydrogenase, and chromatin condensation. In contrast, ER-targeted RIG1 and carboxyterminal-deleted RIG1 (RIG1 Delta C) exhibited no activity. Caspase-2, -3, and -9 were activated following the expression of wild-type and Golgi-targeted RIG]. Although the caspase-3 inhibitor Z-DEVD-FMK partially or completely reversed the cell death induced by wild-type or Golgi-targeted RIG 1, it did not prevent the anti-RAS effect of RIG1. In conclusion, the proapoptotic and anti-RAS activities of RIG I are primarily associated with the Golgi localization of the protein. The proapoptotic activities of RIG I are mediated through the activation of caspase-2 and -3 and are independent of its effect on RAS. (c) 2006 Elsevier Inc. All rights reserved.