温度依赖的Per2蛋白表达的升调是由eIF2α激酶PERK和PKR通过PI3K激活介导的
Xinyan Shao1, Takahito Miyake1, Yuichi Inoue1
1Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University.
Biological & pharmaceutical bulletin
|March 6, 2024
概括
温暖的温度变化通过新型中介来调节核心时钟基因Per2. 蛋白激酶R (PKR) 和类似PKR的内细胞网膜激酶 (PERK) 激活了独立于eIF2α的酸丁醇3-激酶 (PI3K),以控制Per2的表达.
科学领域:
- 循环节生物学 日间生物
- 分子生物学分子生物学
- 细胞信号传输 细胞信号传输
背景情况:
- 昼夜时钟与人体温度周期同步,核心时钟基因Per2对于这一过程至关重要.
- 众所周知,酸丁3-酶 (PI3K) 在温暖温度变化 (WTS) 后调解Per2蛋白表达.
- 除了PI3K之外,控制WTS诱导的Per2表达的精确信号通路仍然在很大程度上未被阐明.
研究的目的:
- 识别参与Per2基因WTS依赖表达的新型信号分子.
- 为了阐明新发现的激酶,PI3K和下游目标eIF2α在WTS的背景下之间的关系.
主要方法:
- 研究了真核启动因子2α (eIF2α) 激酶,特别是蛋白激酶R (PKR) 和PKR类内网膜激酶 (PERK) 在WTS诱导的Per2表达中的作用.
- 通过评估PI3K的激活和eIF2α对WTS的反应的参与来检查信号级联.
主要成果:
- 确定了PKR和PERK作为WTS依赖的Per2蛋白表达的新媒体.
- 证明PERK和PKR激活PI3K在Per2的上游,独立于正规下游目标eIF2α.
- 提供了 PERK/PKR 激活 PI3K 的新信号通路的证据,有助于昼夜时钟的携带.
结论:
- PKR和PERK是Per2表达的WTS响应途径中的关键调节者.
- 这些发现揭示了PERK和PKR在激活PI3K中的非正规作用,与它们已知的eIF2α调节不同.
- 这项研究通过PERK/PKR-PI3K轴将温度传感与Per2调节联系起来,扩大了我们对昼夜时钟引进机制的理解.
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