乳酸通过重塑促复合体来调节细胞循环
Weihai Liu1,2,3, Yun Wang1,2,4, Luiz H M Bozi1,2
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Nature
|March 15, 2023
概括
累积的乳酸通过抑制SENP1直接调节细胞分裂,该SENP1通过SENP1重塑亚纳促进复合体 (APC/C). 这种机制控制了快速分裂的人类细胞的细胞周期进展和增殖.
科学领域:
- 生物化学
- 细胞生物学
- 癌症研究
背景情况:
- 由于高葡萄糖代谢,乳酸在增殖细胞中很丰富.
- 蓄积的乳酸在调节细胞增殖中的作用尚不清楚.
研究的目的:
- 研究人类蛋白质中的乳酸依赖性调节.
- 通过乳酸影响细胞周期进展的机制.
主要方法:
- 系统的蛋白质组分析以确定乳酸调节蛋白.
- 生物化学测试以阐明乳酸,SENP1和APC之间的相互作用.
主要成果:
- 乳酸积累通过抑制SUMO蛋白酶SENP1来重塑亚纳促进复合体 (APC/C).
- 乳酸在SENP1活性部位结合,稳定APC4的SUMOylation,并驱动UBE2C与APC的结合.
- 这种乳酸介导的APC/C调节促进了细胞循环蛋白及时降解和线粒脱落.
结论:
- 乳酸直接调节蛋白质功能以控制细胞循环和增殖.
- 异常的乳酸积累可能导致异常的APC/C重塑和线粒体滑动,可能会克服抗线粒体药物.
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