一个全基因组屏幕将过氧体调节与通过RNF146和TNKS/2的Wnt信号连接起来
Jonathan T Vu1, Katherine U Tavasoli2, Connor J Sheedy1
1Biomolecular Science and Engineering Program, University of California, Santa Barbara , Santa Barbara, CA, USA.
The Journal of cell biology
|July 5, 2024
概括
研究人员确定了RNF146作为Peroxisome蛋白质进口的关键调节器. 这种E3结合酶与TNKS/2一起,影响过氧体恒常,并将过氧体功能与Wnt/β-catenin信号联系起来.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 过氧体是人类发育必不可少的器官,但控制其功能的遗传因素尚未完全理解.
- 识别氧体平衡的新型调节剂对于理解细胞过程和发育至关重要.
研究的目的:
- 通过全基因组的CRISPRi屏幕来识别新型基因和调节Peroxisomal稳态的通路.
- 阐明RNF146在过氧体蛋白进口中的作用及其与其他细胞信号通路的联系.
主要方法:
- 全基因组CRISPR干扰 (CRISPRi) 查,以确定影响过氧体功能的因素.
- 生物化学试验用于研究蛋白质-蛋白质相互作用和酶活性.
- 与Wnt/β-catenin信号传递相关的蛋白质降解和基因转录的分析.
主要成果:
- 抑制RNF146,一个聚基 (ADP-ribose) 激活的E3酶,损害了蛋白质进口到Peroxisomes.
- RNF146对过氧体进口的影响取决于与PEX14相互作用的TNKS和TNKS2的稳定和活性.
- 通过 RNF146 和 TNKS/2 的 PARsylation 调节过氧体进口效率.
- 过氧体的损失增强了RNF146 / TNKS / 2依赖的AXIN1降解,影响β-catenin转录.
结论:
- RNF146在调节过氧酶体功能和蛋白质进口方面发挥着重要的,以前未知的作用.
- 通过RNF146和TNKS/2调节的过氧体平衡与发育过程中的Wnt/β-catenin信号通路之间存在一种新的联系.
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