SENP1 deficiency promotes ER stress-induced apoptosis by increasing XBP1 SUMOylation
SENP1 deficiency promotes ER stress-induced apoptosis by increasing XBP1 SUMOylation
复制标题
SENP1 缺陷通过增加 XBP1 SUMOylation 促进 ER 应激诱导的细胞凋亡
DOI：
10.4161/cc.11.6.19529
复制
发表时间：
2012-03-15
期刊：
影响因子：
4.3
通讯作者：
Cheng, Jinke
中科院分区：
文献类型：
--
作者：
Jiang, Zhou;Fan, Qiuju;Cheng, Jinke
转录因子X盒结合蛋白1（XBP 1）是内质网（ER）应激反应的关键组分。最近，有报道称，剪接的XBP 1（XBP 1 s），在ER应激过程中被激活的XBP 1，可以被SUMO化。在这里，我们将Sentrin/SUMO特异性蛋白酶1（SENP 1）鉴定为XBP 1的特异性去SUMO化蛋白酶。SENP 1可以增强XBP 1的转录活性。在Senp 1-/-细胞中，SUMO化的XBP 1积累，并且响应于ER应激，XBP 1靶基因的表达下调。此外，SENP 1缺陷通过积累XBP 1 SUMO化显著增加ER应激诱导的细胞凋亡。这些结果揭示了SENP 1通过调节XBP 1 SUMO化在内质网应激反应中的重要功能。
The transcription factor X box-binding protein 1 (XBP1) is a key component of the endoplasmic reticulum (ER) stress response. Recently, it has been reported that the spliced XBP1 (XBP1s), an activated XBP1 during ER stress, can be SUMOylated. Here, we identify Sentrin/SUMO-specific protease 1 (SENP1) as a specific de-SUMOylation protease for XBP1. SENP1 can increase the transcriptional activity of XBP1. In Senp1-/- cells, the SUMOylated XBP1 is accumulated, and the expression of XBP1 target genes is downregulated in response to ER stress. Moreover, SENP1 deficiency significantly increases ER stress-induced apoptosis through accumulating XBP1 SUMOylation. These results reveal an essential function of SENP1 in ER stress response through regulating XBP1 SUMOylation.