TECPR1是由损伤诱导的基米林暴露中介于非正规的自细胞激活的
Namrita Kaur1,2, Laura Rodriguez de la Ballina1,3, Håvard Styrkestad Haukaas1,2
1Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Oslo, Norway.
The EMBO journal
|July 6, 2023
概括
含有TECPR1的E3复合体是非正规自的关键媒介 (CASM),标记受损的细胞区域. 这一过程是通过对ATG16L1独立的髓暴露激活的,揭示了一个新的信号通路.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 自学研究 自学研究
背景情况:
- 非正规的自,或ATG8与单膜的结合 (CASM),标记受损的细胞区域以信号危险.
- CASM利用E3复合体来感知膜损伤,以前只有ATG16L1含有复合体被理解,与质子梯度损失有关.
研究的目的:
- 调查TECPR1-含有E3复合体在CASM中的作用.
- 阐明TECPR1调解CASM激活的机制.
主要方法:
- 用各种药理剂对细胞进行处理,包括纳米颗粒,转染试剂和洗剂.
- 在沙门氏菌Typhimurium病原性因子SopF的存在下调查TECPR1活动.
- 在体外测试中使用纯化的人类TECPR1-ATG5-ATG12和ATG16L1-ATG5-ATG12复合体.
主要成果:
- 含有TECPR1的E3复合体被确定为CASM在各种细胞攻击中的关键调解者.
- 即使ATG16L1CASM活性受到抑制,TECPR1也保留了E3活性.
- 通过损伤诱导的髓 (SM) 暴露,TECPR1被招募并激活,导致ATG8脂化.
- 实验室研究证实,SM直接激活了TECPR1 E3活动,而ATG16L1 E3活动不受SM的影响.
结论:
- TECPR1是CASM的关键激活剂,在暴露于髓后下游运作.
- 这一发现扩大了对CASM调节及其对细胞损伤的反应的理解.
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