对JMJD2B表观遗传调节器的甲基化不同影响其协同激活ETV1和JUN转录因子的能力
Tae-Dong Kim1, Ruicai Gu1, Ralf Janknecht1,2,3
1Department of Cell Biology, University of Oklahoma Health Sciences Center Oklahoma, OK, USA.
International journal of biochemistry and molecular biology
|January 12, 2024
概括
由SET7/9对含有2B Jumonji C域 (JMJD2B) 的氨酸甲基化影响其在前列腺癌中的功能. 这种修改影响了与JUN等特定转录因子的合作,这表明它在瘤发生过程中发挥了作用.
科学领域:
- 表观遗传学和癌症生物学
- 后翻译修改 后翻译修改
- 转录条例 转录条例 转录条例
背景情况:
- 含有C域2B的Jumonji (JMJD2B) 是一种基因素脱甲基酶和转录辅因子,涉及前列腺癌.
- 通过翻译后修改,特别是氨酸甲基化来调节JMJD2B功能以前没有被描述.
研究的目的:
- 调查JMJD2B是否通过氨酸甲基化进行调节.
- 确定负责JMJD2B甲基化的甲基转移酶,并评估这种修饰的功能后果.
主要方法:
- 在体外甲基化试验和使用甲基-氨酸特异性抗体检测JMJD2B甲基化.
- 鉴定出氨酸残留物对氨酸和记者基因分析的局部定向突变发生,以测量LNCaP前列腺癌细胞中的转录活性.
主要成果:
- 发现JMJD2B在多达六个氨酸残留物上被甲基化,其中SET7/9被确定为负责的甲基转移酶.
- 甲基化位点的突变降低了JMJD2B对瘤转录因子JUN的同激活,但不是ETV1.
- 在人类前列腺瘤中,JMJD2B,SET7/9和JUN表达水平与正相关.
结论:
- 通过SET7/9介导的JMJD2B甲基化影响其与特定的转录因子的相互作用,影响前列腺癌细胞的功能.
- 这种甲基化也可能在其他癌症,肥胖和与JMJD2B活性相关的发育迟缓中发挥作用.
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