JMJD6和YBX1在物理上相互作用并调节HOTAIR近位促进物
Aritra Gupta1,2, Siddharth Bhardwaj1, Kartiki V Desai1,2
1Biotechnology Research Innovation Council-National Institute of Biomedical Genomics (BRIC-NIBMG), Kalyani, West Bengal, India.
The Biochemical journal
|August 26, 2025
概括
Y盒子相互作用蛋白1 (YBX1) 将含有蛋白6 (JMJD6) 的jumonji域与HOTAIR促进体相连接,从而推动瘤的进展. 这种相互作用创造了一个积极的反循环,增强了乳腺癌中的HOTAIR表达.
科学领域:
- 分子生物学
- 癌症研究
- 表观遗传学
背景情况:
- 之前的研究发现了含有与HOTAIR促进体结合的 jumonji 域.
- 进一步的调查显示,在JMJD6结合地点上游还有一个监管区域.
- 在Silico和ENCODE数据表明Y盒相互作用蛋白1 (YBX1) 与上游区域结合.
研究的目的:
- 在乳腺癌细胞系中验证JMJD6和YBX1之间的相互作用.
- 阐明JMJD6-YBX1相互作用对HOTAIR表达的功能后果.
- 确定YBX1对HOTAIR发起人的JMJD6招募的影响机制.
主要方法:
- 共同免疫沉测试以确认蛋白质与蛋白质的相互作用.
- 使用删除构造进行域映射.
- 路西法雷斯的记者测量来评估主办人的活动.
- 通过siRNA介导的衰减和基因淘汰 (YKO) 来研究功能性影响.
- 染色体免疫沉 (ChIP和ChIP-re-ChIP) 和电泳运动转移测试 (EMSA).
主要成果:
- JMJD6和YBX1直接相互作用,YBX1的A/P域与JMJD6的JMJC域结合.
- YBX1增强了HOTAIR促进剂的活性,而YBX1相互作用区域 (YIR) 的枯竭或突变降低了活性.
- JMJD6和YBX1都是HOTAIR的发起人,而YBX1对JMJD6的招募至关重要.
- 在JMJD6和YBX1相互调节对方的表达时,存在一个正向输入循环,导致HOTAIR诱导的增加.
结论:
- 在乳腺癌细胞中,YBX1对于JMJD6的HOTAIR促进剂的招募至关重要.
- JMJD6-YBX1相互作用和它们的正反循环驱动HOTAIR表达.
- 这种机制有助于瘤的进展,强调JMJD6和YBX1作为潜在的治疗点.
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