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在应对氧化应激的过程中,TRIM44通过SQSTM1的寡合化增强了自
Yuqin Wang1, Lin Lyu1, Trung Vu1
1Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM), The University of Texas-Health Science Center at Houston, 1825 Pressler St., IMM-630A, Houston, TX, 77030, USA.
Scientific reports
|August 16, 2024
概括
含有44 (TRIM44) 的三部分基因在氧化应激下增强了自,减少了癌细胞死亡. 它调节了顺序素-1 (SQSTM1) 酸化,影响了氧化应激反应.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 含有44 (TRIM44) 的三部分基因是一种二基因酶,对于将蛋白质毒性压力与自性降解联系起来至关重要.
- TRIM44是癌症的预后标记物,但它在氧化应激诱导的自中所起的作用尚未完全理解.
研究的目的:
- 阐明TRIM44在氧化应激下促进自的分子机制.
- 研究TRIM44在调节序列酶-1 (SQSTM1) 的作用及其对癌细胞存活率的影响.
主要方法:
- 研究了TRIM44对暴露于氧化应激 (三氧化) 的癌细胞自的作用.
- 分析了TRIM44介导的SQSTM1.4的翻译后修饰和寡合化.
- 研究了TRIM44,蛋白激酶A和SQSTM1之间的相互作用,包括SQSTM1在S349.9的酸化.
- 评估了NFE2L2 (核因子红色素2相关因子2) 的激活,以应对TRIM44活动.
主要成果:
- 在氧化应激下,TRIM44显著增强了自,并降低了癌细胞在氧化应激下的细胞毒性.
- TRIM44通过PB1域和氧化依赖途径促进SQSTM1的寡合化.
- TRIM44放大蛋白激酶A与SQSTM1的相互作用,增强SQSTM1在S349.9的酸化.
- 化SQSTM1激活NFE2L2,表明TRIM44在氧化应激反应调节中的作用.
结论:
- TRIM44在调节对氧化应激的自敏感性方面发挥着关键作用.
- TRIM44对SQSTM1酸化的调节是其在氧化应激反应和自的功能中的关键.
- 这些发现对癌症,衰老,与衰老相关的疾病和神经退行性疾病有影响.
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