通过JNK开关进行酸化,使BRD4功能发挥作用
Ballachanda N Devaiah1, Amit Kumar Singh1, Jie Mu1
1Experimental Immunology Branch, NCI, NIH, Bethesda, MD 20892, USA.
Molecular cell
|October 25, 2024
概括
odomain 4 (BRD4) 开关通过JNK酸化起作用,从染色质释放以激活转录. 这种开关是免疫反应和癌症进展的关键.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- odomain 4 (BRD4) 是癌症和细胞压力的关键调节剂.
- BRD4具有双重作用:通过HAT活性重塑染色质,通过激酶活性调节转录.
- BRD4的活性取决于环境,在与染色质相结合时具有不同的功能,而不是促进剂.
研究的目的:
- 阐明BRD4在染色质调节和转录激活之间的功能切换背后的机制.
- 调查c-Jun N-终端激酶 (JNK) 在调解BRD4功能转换中的作用.
主要方法:
- 人类BRD4.4的酸化部位映射.
- 在刺激时从染色质中释放BRD4的分析.
- 对RNA聚合酶II (RNA Pol II),PTEFb和c-Myc.的BRD4激酶活性的评估.
- 在胸细胞和前列腺癌细胞中评估BRD4介导的基因表达变化.
主要成果:
- 在Thr1186和Thr1212的BRD4的JNK介导酸化诱导其从染色质释放.
- 释放的BRD4表现出增强的激酶活性,酸化RNA Pol II,PTEFb和c-Myc.
- 这种功能性开关促进了免疫/炎症基因的转录,胸细胞中的CD8表达,以及前列腺癌中的上皮转介质过渡 (EMT).
结论:
- 通过JNK介导的酸化是BRD4功能切换的关键机制.
- 通过JNK信号传递,BRD4从染色质修饰剂过渡到转录激活剂.
- 这种开关对免疫反应和癌症的发展,特别是前列腺癌,有重大影响.
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