依赖ATG结合的/独立的机制是溶酶体压力诱导的TFEB调节的基础
Shiori Akayama1,2, Takayuki Shima2,3, Tatsuya Kaminishi4
1Graduate School of Frontier Biosciences, Osaka University , Suita, Japan.
The Journal of cell biology
|August 29, 2025
概括
这项研究揭示了细胞应激过程中TFEB (转录因子EB) 调节的两种新模式. 模式I涉及TFEB稳定性的APEX1,而模式II使用CCT7/TRIP6来阻止激活,提供TFEB控制的统一视图.
科学领域:
- 细胞生物学
- 分子生物学
- 生物化学
背景情况:
- 转录因子EB (TFEB) 是自和溶酶生物发生的关键调节剂.
- TFEB的激活是由细胞应激引起的,包括 lysosomal损伤,但其调节机制仍然不完全理解.
- 现有知识将在 lysosomal 损伤期间的 TFEB 激活与修改 ATG8 蛋白质的 ATG 结合系统联系起来.
研究的目的:
- 阐明细胞应激过程中TFEB激活的潜在机制.
- 确定涉及TFEB监管的新型监管者和途径.
- 建立对各种细胞应激反应的TFEB调节机制的统一理解.
主要方法:
- 研究了在溶酶体损伤期间的TFEB调节,区分了ATG结合依赖和独立的通路.
- 鉴定和描述了新的TFEB调节剂:APEX1 (模式I) 和CCT7/TRIP6 (模式II).
- 使用生物化学测定和基于细胞的研究来分析蛋白质相互作用和TFEB稳定性/激活性.
主要成果:
- 发现了一种ATG结合独立的TFEB调节 (模式I) 涉及APEX1,增强了TFEB稳定性.
- 通过CCT7和/或TRIP6介导的ATG结合依赖TFEB调节 (模式II) 被发现,这些调节似乎阻断了TFEB激活.
- 证明I模式和II模式都参与各种细胞应激的TFEB激活,这表明它们具有更广泛的调节作用.
结论:
- TFEB 监管至少涉及两种不同的模式,一种是独立的,另一种是依赖于 ATG 连接系统的.
- 在不同的压力条件下,APEX1,CCT7和TRIP6被确定为TFEB监管的新关键参与者.
- 这些发现为了解TFEB在细胞应激反应中的作用提供了更全面的框架.
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