RIP3/MLKL通过激活4EBP1-eIF4E通路来调节亡
1Center for Medical Research, Second Xiangya Hospital, Central South University, Changsha 410011. wangshuchao@csu.edu.cn.
概括
细胞转化启动因子4E-结合蛋白1 (4EBP1) -细胞转化启动因子4E (eIF4E) 途径在受体相互作用蛋白3 (RIP3) /混合系基因酶域样蛋白 (MLKL) 介导的亡过程中被激活. 这项研究研究了这种途径在亡中的作用.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 亡是细胞死亡的一个规范形式.
- 受体相互作用蛋白3 (RIP3) 和混合基因酶域样蛋白 (MLKL) 介导死亡.
- 哺乳动物的拉巴胺素 (mTOR) 途径的标通过真核转化启动因子4E结合蛋白1 (4EBP1) -真核启动因子4E (eIF4E) 轴调节亡.
研究的目的:
- 为了调查4EBP1-eIF4E途径在亡中的参与.
- 为了确定在RIP3/MLKL介导的亡过程中4EBP1和eIF4E表达的变化.
主要方法:
- 在L929细胞中使用TNF-α/SM-164/Z-VAD-FMK (TSZ) 诱导了亡.
- 使用RIP3和MLKL基因淘汰L929细胞来确认特异性.
- 细胞亡通过光学显微镜和酸 (PI) 染色来评估.
- 使用实时PCR和西式涂抹测量了4EBP1和eIF4E的mRNA和蛋白质表达量.
主要成果:
- 治疗TSZ增加了亡,降低了4EBP1的调节,并提高了eIF4E的调节.
- 4EBP1和eIF4E的酸化在死亡诱导时增加.
- 在RIP3/MLKL淘汰赛细胞中,死亡细胞减少,4EBP1表达增加,eIF4E表达减少.
结论:
- 在RIP3/MLKL介导的亡过程中,4EBP1-eIF4E通路被激活.
- 这一途径在死细胞的生长过程中起着重要作用.
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