TDRD3-USP9X复合体和MIB1调节TOP3B的平衡,并防止有害的TOP3B裂解复合体
Sourav Saha1, Shar-Yin Naomi Huang1, Xi Yang1
1Developmental Therapeutics Branch & Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.
Nature communications
|November 18, 2023
概括
TDRD3通过招募USP9X来稳定TOP3B,以防止其退化. 丢失TDRD3导致TOP3B积累和DNA损伤,突出了TDRD3的存在.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- TOP3B 是一种关键的蛋白质,与DNA拓有关.
- 众所周知,TDRD3可以稳定TOP3B.
- 通过TDRD3稳定TOP3B的精确机制尚未完全理解.
研究的目的:
- 阐明TDRD3稳定TOP3B的分子机制.
- 调查二维基基因酶在TOP3B调控中的作用.
- 了解细胞中TOP3B积累的后果.
主要方法:
- 同免疫沉以研究蛋白质相互作用.
- 西方涂抹以评估蛋白质水平和无处不在.
- 通过siRNA介导的基因枯竭.
- 测量TOP3B-DNA/RNA结合体 (TOP3Bccs) 的情况.
- 对DNA损伤标记物 (γH2AX) 和R循环形成的分析.
主要成果:
- TDRD3将USP9X招募到TOP3B,调解其二维化和稳定.
- MIB1在TOP3B上无处不在,导致其蛋白质体降解,独立于TDRD3.
- TDRD3和USP9X的耗尽不会增加TOP3B的无处不在.
- 失去TDRD3会增加TOP3Bccs,诱导R循环和γH2AX,并导致生长缺陷.
- TDRD3促进了TOP3B的循环,保护细胞免受有害的TOP3Bccs的影响.
结论:
- 该TDRD3-USP9X复合物对TOP3B进行二氧化和稳定,抵消MIB1介导的降解.
- TDRD3对于防止TOP3Bccs的积累至关重要,从而保持基因组稳定性和细胞生长.
- TRIM41参与了TOP3Bccs的去除工作.
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