同一个在menin中的口袋绑定了MLL和JUND,但对转录有相反的影响
Jing Huang1, Buddha Gurung, Bingbing Wan
1Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Nature
|February 14, 2012
概括
梅宁蛋白质是一种蛋白质.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 梅宁是一种瘤抑制蛋白,与多重内分泌瘤1 (MEN1) 有关.
- 梅宁与JUND和MLL1等蛋白质的相互作用对细胞过程至关重要.
- 了解menin的多种蛋白质相互作用是其瘤抑制功能的关键.
研究的目的:
- 阐明men与MLL1和JUND的相互作用背后的结构机制.
- 了解menin对不同合作伙伴的约束如何影响转录调节.
- 提供关于男性在MEN1和白血病发生中的作用的结构性见解.
主要方法:
- 使用X射线晶体学来确定人体脑膜的结构.
- 结构是免费获得的,并与MLL1,JUND和MLL1-LEDGF异构体复合.
- 对这些结构的分析揭示了男性功能的约束模式和结构基础.
主要成果:
- 梅宁有一个深层口袋,可以类似地从MLL1和JUND结合.
- 梅宁与JUND结合,通过阻断JNK介导的酸化来抑制其转录活性.
- 梅宁作为MLL1的辅因子,通过将MLL1与染色质上的LEDGF架桥来促进转录.
结论:
- 梅宁的结构性适应性使其能够与多种合作伙伴相互作用,从而导致对立的转录结果.
- 阴阴-JUND相互作用抑制转录,而阴阴-MLL1-LEDGF相互作用促进它.
- 这些发现澄清了menin作为分子适应器在瘤抑制和瘤发生中的作用.
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