| 谷晓峰 邓学峰 马群风 郁苗 Muhammad Arshad 周林康.RNF13通过IRE1/XBP-1 通路调控内质网应激介导的细胞凋亡[J].,2016,16(5):801-805 |
| RNF13通过IRE1/XBP-1 通路调控内质网应激介导的细胞凋亡 |
| RNF13 Mediates ER Stress induced Apoptosis through IRE1/XBP-1Pathway |
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| DOI： |
| 中文关键词: 内质网应激 细胞凋亡 RNF13 IRE1 XBP1 |
| 英文关键词: ER stress Apoptosis RNF13 IRE1 XBP1 |
| 基金项目:中国博士后科学基金资助项目（2013T60103，2012M520249） |
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| 中文摘要: |
| 目的：在研究内质网应激介导的细胞凋亡过程中，我们发现Ring finger protein13(RNF13)具有促进细胞凋亡的功能。我们拟
研究沉默RNF13 后细胞对Tunicamycin 等引起的细胞凋亡的影响，以及RNF13 对活性形式的caspase3，XBP1（X-box binding
protein 1）的剪切以及IRE1（Endoplasmic reticulum to nucleus signaling 1）磷酸化的影响以有助于了解RNF13 促进细胞凋亡的信
号通路的研究。方法：基因沉默RNF13，利用MTT方法研究RNF13 沉默后对细胞增殖的影响，RNF13基因沉默后对XBP1剪切
的影响，免疫印迹观察RNF13 对IRE1 磷酸化的影响。结果：RNF13 基因沉默效率在80%以上。RNF13基因沉默后明显抑制细胞
凋亡；敲低RNF13 的细胞可抵抗衣霉素以及毒胡萝卜素的诱导的细胞凋亡。Caspase-3 是细胞凋亡的关键蛋白。敲低RNF13 后
caspase-3 的活性形式明显降低（降低70%，P<0.001）。在加入衣霉素引起内质网应激的情况下，敲除RNF13的细胞XBP1 的切割
活性明显降低。敲除RNF13 的细胞中IREl的磷酸化明显降低（降低90%，P<0.001）。结论：RNF13 通过IRE1-XBP1信号通路调节
细胞凋亡。 |
| 英文摘要: |
| Objective:While studying ER stress，we found that Ring finger protein 13 (RNF13) have some functions related to
apoptosis. Here, we want to investigate the molecular mechanism that how RNF13 regulate apoptosis. We want to check the expression
level of active caspase3, XBP1 splicing and IRE1 phosphorylation level after RNF13 was knockdown.Methods:RNA extraction were
performed using siNC and siRNF13 cells. Cells were treated with Tunicamycin and MTT experiment was performed to measure cell
growth. Caspase3 protein level were tested in RNF13 knockdown. Next, XBP1 cleavage and IRE1 phosphorylation were tested in control
and RNF13 knockdown cells.Results:RNF13 stable knockdown cell line were obtained, the knockdown efficiency was good (80% reduction).
RNF13 knockdown cells were resistant to Tunicamycin and staurosporine induced apoptosis. The expression level cleavaged
caspase 3 was reduced dramatically when RNF13 was knockdown compared with that of control cells, indicating reduced cell apoptosis
in RNF13 depletion condition. RNF13 knockdown cells showed lower activity of XBP1 splicing. The phosporylation of IRE1 was dramatically
reduced when RNF13 was knockdown. RNF13 depletion dramatically downregulated the IRE1-XBP1 signalling pathway.Conclusion:RNF13 regulates ER stress induced apoptosis through IRE1-XBP1 signal pathway. |
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