氨基-tRNA合成酶通过一种非翻译机制激活STAT3
Pallob Barai1, Reean Abdullah1, Shruti V Bendre2
1Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
The Journal of biological chemistry
|December 11, 2025
概括
信号转换器和转录3激活器 (STAT3) 是由氨酸-tRNA合成酶1 (TARS1) 激活的,这是一种与肺癌存活率差相关的蛋白质. TARS1充当了支架,将STAT3和JAK结合在一起,促进癌细胞的增殖.
科学领域:
- 分子生物学分子生物学
- 癌症生物学 癌症生物学
- 生物化学 生物化学
背景情况:
- 信号转换器和转录3激活器 (STAT3) 是细胞生长和存活的关键调节器,在各种癌症中经常失调.
- 异常的STAT3激活是许多恶性瘤的标志,推动瘤的进展和对治疗的抵抗.
研究的目的:
- 为了确定癌症中STAT3激活的新型调节者.
- 为了研究三烯-tRNA合成酶1 (TARS1) 在STAT3信号和非小细胞肺癌 (NSCLC) 中的作用.
主要方法:
- 对TARS1表达与肺癌患者存活率的相关性分析.
- 在体外研究评估TARS1过度表达对NSCLC细胞增殖的影响.
- 在活体外移植小鼠模型中,评估TARS1对瘤形成的影响.
- 生物化学测试以确定TARS1,STAT3和Janus激酶 (JAK) 之间的相互作用.
- 在非癌细胞中进行复制实验.
主要成果:
- 肺癌中TARS1表达升高与患者存活率降低相关.
- 过度表达TARS1增强NSCLC细胞增殖,异种移植瘤生长和STAT3过活.
- 在催化上不活跃的TARS1保留了激活STAT3和促进细胞增殖的能力,这表明它具有非翻译功能.
- TARS1与STAT3和JAK进行物理相互作用,需要基底JAK活性才能激活STAT3.
- 提出了一个支架模型,TARS1促进了STAT3-JAK的接近,从而导致STAT3的酸化.
结论:
- 在癌症中,TARS1是STAT3的新型非正规激活剂.
- TARS1的支架功能促进STAT3介导的细胞增殖和瘤生长.
- 针对TARS1的非翻译性作用,为肺癌提供了潜在的治疗策略.
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