XBP1S protects cells from ER stress-induced apoptosis through Erk1/2 signaling pathway involving CHOP (Retracted Article)
XBP1S protects cells from ER stress-induced apoptosis through Erk1/2 signaling pathway involving CHOP (Retracted Article)
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DOI：
10.1007/s00418-012-0967-7
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发表时间：
2012-09-01
影响因子：
2.3
通讯作者：
Liu, Chuanju
中科院分区：
文献类型：
--
作者：
Guo, Feng-Jin;Liu, Yanna;Liu, Chuanju
哺乳动物未折叠蛋白反应（UPR）保护细胞免受内质网（ER）中错误折叠蛋白的应激，并且已知转录因子X-box结合蛋白1剪接体（X-box binding protein 1 spliced，XBP 1 S）（UPR的调节剂）对于ER应激（ERS）介导的细胞凋亡和细胞生长是重要的，但是这些过程的分子机制仍然未被探索。在这里，我们报告说，敲低XBP 1 S的siRNA沉默方法增加了ERS相关分子的表达。在软骨细胞和软骨肉瘤细胞中，XBP 1 S的过表达刺激细胞增殖，而其敲低抑制细胞增殖;此外，XBP 1 S的过表达抑制软骨细胞和软骨肉瘤细胞中ERS介导的细胞凋亡，而其抑制增强。此外，XBP 1 S通过Erk 1/2信号通路和下调CHOP转录因子介导的ERS诱导的细胞凋亡抑制。CHOP是已知参与ERS介导的细胞凋亡的关键下游分子之一。总的来说，这些发现揭示了一个新的关键作用，在ERS介导的细胞凋亡和相关的分子机制的XBP 1 S。
The mammalian unfolded protein response (UPR) protects the cell against the stress of misfolded proteins in the endoplasmic reticulum (ER), and the transcription factor X-box binding protein 1 spliced (XBP1S), a regulator of the UPR, is known to be important for ER stress (ERS)-mediated apoptosis and cell growth, but the molecular mechanism underlying these processes remains unexplored. Here, we report that knockdown of XBP1S by an siRNA silencing approach increased the expression of ERS-associated molecules. The overexpression of XBP1S stimulated, whereas its knockdown inhibited, cell proliferation in chondrocytes and chondrosarcoma cells; in addition, overexpression of XBP1S inhibited, while its repression enhanced, ERS-mediated apoptosis in chondrocytes and chondrosarcoma cells. Furthermore, XBP1S-mediated inhibition of apoptosis in response to ERS is through the Erk1/2 signaling pathway and down-regulation CHOP transcription factor. CHOP is one of the key downstream molecules known to be involved in ERS-mediated apoptosis. Collectively, these findings reveal a novel critical role of XBP1S in ERS-mediated apoptosis and the molecular mechanisms involved.