NEMO/NLK酸化物周期启动时间延迟酸化电路,设置昼夜时钟速度
Joanna C Chiu1, Hyuk Wan Ko, Isaac Edery
1Department of Molecular Biology and Biochemistry, Rutgers University, Center for Advanced Biotechnology and Medicine, Piscataway, NJ 08854, USA.
Cell
|April 26, 2011
概括
动物的昼夜时钟速度是由PERIOD蛋白质的等级酸化调节的. 这项研究揭示了一个时间延迟电路控制蛋白质降解,设置日常生物节奏的节奏.
科学领域:
- 时间生物学 时间生物学
- 分子和细胞生物学分子和细胞生物学
- 生物化学 生物化学
背景情况:
- 动物的循环时钟速度是由PERIOD (PER) 蛋白质的复杂酸化调节的.
- 每日PER蛋白水平的周期对于维持生物节奏至关重要.
研究的目的:
- 为了阐明控制PER蛋白丰富度每日下降的时间延迟电路.
- 确定NEMO/NLK激酶在PER蛋白的酸化级联中的作用.
主要方法:
- 研究了Drosophila中PER蛋白的层次酸化.
- 分析了多站位酸化的空间和分级性质.
- 研究了酸化后PER蛋白的结构变化.
主要成果:
- 确定了一种涉及PER蛋白质等级酸化的时间延迟电路.
- NEMO/NLK激酶在特定部位刺激双倍时间 (DBT) 酸化.
- 渐进酸化增加了PER蛋白对蛋白质体降解的敏感性,控制了时钟速度.
结论:
- NEMO被确定为一个关键的时钟激酶.
- 层次酸化和远程聚物相互作用调节昼夜时钟速度.
- 这项研究提供了关于昼夜节律计时的基础分子机制的见解.
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