TRAF7通过DBP的无处不在和降解来确定昼夜周期
Shusaku Masuda1, Nobuhiro Kurabayashi2, Rina Nunokawa1
1Department of Biological Sciences, School of Science, The University of Tokyo, Tokyo, Japan.
Communications biology
|October 8, 2024
概括
瘤亡因子受体相关因子7 (TRAF7) 通过无素-蛋白酶体通路破坏D位结合蛋白 (DBP) 的稳定,调节昼夜节律. 这项研究揭示了控制日常生理过程的关键机制.
科学领域:
- 循环节生物学 循环节生物学
- 循环时钟的分子机制
- 翻译后修改 翻译后修改
背景情况:
- D位点结合蛋白 (DBP) 是一个关键的转录因子,通过D盒基因调节日常生理节奏.
- DBP表现出强大的昼夜振荡,但控制其时间模式的翻译后机制仍然不清楚.
研究的目的:
- 阐明DBP蛋白水平的翻译后调节及其在昼夜钟功能中的作用.
- 确定负责DBP降解的E3结合酶及其对昼夜振荡的影响.
主要方法:
- 使用主导负E2酶来识别DBP降解中的UBE2G1和UBE2T.
- 进行蛋白质组分析和数据库选,以确定TRAF7是与DBP相互作用的E3结合酶.
- 在NIH3T3细胞中进行了ubiquitination测定,细胞培养实验和TRAF7淘汰研究.
主要成果:
- TRAF7增强了K48相关的多比基化和DBP的降解.
- 在TRAF7中,过度表达降低了DBP的水平,而在TRAF7中降低了DBP的水平.
- TRAF7淘汰破坏了依赖于一天时间的DBP调节,并缩短了细胞时钟周期.
结论:
- TRAF7是DBP蛋白稳定性和昼夜时钟振荡的关键调节者.
- 由TRAF7,UBE2G1和UBE2T介导的泛素-蛋白酶体通路控制着DBP水平.
- 在维持昼夜节律的稳定性和定时性方面,TRAF7起着至关重要的作用.
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