UBE3C通过ATG4B无处不在调节自
Chaonan Sun1, Yuxin Chen1, Qianqian Gu1
1School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Autophagy
|December 26, 2023
概括
研究人员将UBE3C确定为一种E3结合酶,该结合酶特别在ATG4B上无处不在,ATG4B是自的一个关键蛋白质. 这种无处不在的微调调整了ATG4B的活动,并调节了自流,而不会导致蛋白质降解.
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:
- 自是一种由ATG4B等蛋白调节的关键细胞过程.
- ATG4B的稳定性和活性是通过翻译后的修改来调节的,特别是无处不在.
- 控制ATG4B无处不在的具体机制在很大程度上是未知的.
研究的目的:
- 为了确定调节ATG4B无处不在的新型E3链酶.
- 阐明UBE3C在ATG4B修饰中的作用及其对自的影响.
- 为了研究ATG4B无处不在如何影响在不同的细胞条件下自流.
主要方法:
- 质谱法用于识别潜在的ATG4B相互作用的E3链酶.
- 进行了ubiquitination测试,以通过UBE3C分析ATG4B上的ubiquitination的类型和位置.
- 自流被评估在细胞改变了UBE3C或ATG4B表达/突变.
- 免疫沉被用于在饥饿条件下研究蛋白质与蛋白质相互作用.
主要成果:
- UBE3C被确定为ATG4B的新型E3结合酶,在Lys119.9.中催化K33分支的泛素链组合.
- 通过UBE3C介导的ATG4B的泛基化通过降低ATG4B的活性及其与LC3.3的相互作用来抑制自流.
- 这种抑制作用可以通过将ATG4B的Lys119突变为阿金来逆转.
- 在饥饿状态下,UBE3C与ATG4B的相互作用减少,导致K33分支 ubiquitin链的去除和部分抑制饥饿诱导的自.
结论:
- UBE3C通过特定的无处不在调节ATG4B活动,调节自而不会诱导ATG4B降解.
- 这项研究揭示了一种新的自的调节机制,涉及UBE3C介导的ATG4B无处不在.
- 这些发现为通过特定的无处不在模式对自流动的动态调节提供了新的见解.
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