经营ER的贩运触发了NRF1的无处不在,以促进其蛋白质溶解活性
Claire Chavarria1, Léa Zaffalon1, Sérgio T Ribeiro1
1Department of Immunobiology, University of Lausanne, 155 Ch. des Boveresses, 1066 Epalinges, Switzerland.
iScience
|September 18, 2023
概括
细胞内膜网膜 (ER) 调节转录因子NRF1 (核因素红色素2相关因子1) 通过编排其无处不在. 这一过程对于NRF1激活和蛋白酶体功能恢复至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 蛋白质调节的分子机制
- 蛋白质稳定和细胞应激反应
背景情况:
- 核因子红色素2相关因子1 (NRF1) 是一种转录因子,局部存在于内分泌网膜 (ER).
- NRF1通常被蛋白质酶体降解,但在蛋白质酶体功能障碍时逃脱了降解.
- 激活的NRF1恢复蛋白质稳定,包括蛋白质酶功能,但调节机制尚不清楚.
研究的目的:
- 阐明控制NRF1蛋白质分解活性和转录潜力的调节机制.
- 为了研究内细胞网膜 (ER) 在NRF1调节中的作用.
- 确定参与NRF1处理和激活的关键蛋白质.
主要方法:
- 在细胞模型中研究了NRF1由E3泛素酶HRD1的泛素化.
- 评估了HRD1介导的全方位化对于DDI2介导的NRF1处理的必要性.
- 研究了RAD23A和RAD23B缺陷对DDI2介导的NRF1处理的影响.
主要成果:
- 该ER在NRF1功能中发挥着至关重要的作用,通过HRD1.1编排其无处不在.
- 为了使NRF1由蛋白酶DDI2.2进行处理,需要HRD1介导的NRF1的泛化.
- 在RAD23A和RAD23B中缺陷会损害DDI2介导的NRF1处理,突出显示它们在DDI2机制中的作用.
结论:
- ER是NRF1激活的关键调节者,通过HRD1-介导的全方位激活.
- 通过HRD1进行乌比基化对于DDI2依赖的裂变和NRF1.1的激活至关重要.
- RAD23A和RAD23B是用于NRF1处理的DDI2蛋白质溶解系统的组成部分,协调细胞适应反应.
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