翻译后机制调节哺乳动物的昼夜时钟
C Lee1, J P Etchegaray, F R Cagampang
1Department of Neurobiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Cell
|January 10, 2002
概括
鼠肝时钟蛋白 (mPER1, mPER2, CLOCK, BMAL1) 显示每天的酸化变化. 密码染色体 (mCRY1,mCRY2) 对于稳定这些蛋白质和确保为昼夜节律调节核积累至关重要.
科学领域:
- 时间生物学 时间生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 循环节律是内生生物过程,在约24小时内振荡.
- 核心分子时钟机械涉及转录-翻译反循环.
- 翻译后的修改,如酸化,在调节时钟蛋白的稳定性和功能的过程中起着至关重要的作用.
研究的目的:
- 研究小鼠肝脏中核心时钟蛋白的翻译后调节.
- 阐明加密染色体 (mCRY1,mCRY2) 在时钟蛋白的稳定性和局部化中的作用.
- 为了识别参与时钟蛋白的昼夜调节的激酶.
主要方法:
- 在小鼠肝脏中钟表蛋白酸化的体内分析.
- 同免疫沉研究蛋白质复合体的形成.
- 在密码色素缺陷小鼠中分析时钟蛋白的行为.
主要成果:
- 鼠标的PERIOD蛋白 (mPER1,mPER2),CLOCK和BMAL1都表现出日间依赖的酸化.
- CLOCK:BMAL1异构体在整个昼夜循环中结合DNA.
- 加密染色体 (mCRY1,mCRY2) 对于稳定化mPER2和促进mPER1,mPER2和CKIepsilon的核进入至关重要.
- 氨酸激酶I delta被确定为一种新的时钟相关激酶.
结论:
- 翻译后调节,特别是酸化,是控制小鼠肝脏昼夜时钟功能的关键机制.
- 加密染色体对于PERIOD蛋白和CKIepsilon的稳定性和核定位至关重要.
- 氨酸激酶I三角体代表了对已知的激酶调节哺乳动物昼夜时钟的显著增加.
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