53受 lysine 脱甲基酶 LSD1 的调节
Jing Huang1, Roopsha Sengupta, Alexsandra B Espejo
1The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
Nature
|September 7, 2007
概括
瘤抑制剂p53通过氨酸甲基化和脱甲基化进行调节. 脱甲基酶LSD1通过逆转特定的甲基化标记来控制p53的活性,从而影响基因激活和亡.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症研究 癌症研究
背景情况:
- p53是一种关键的瘤抑制剂,通过像氨酸甲基化这样的翻译后修饰来调节.
- 已知基因组 lysine 甲基化是可逆的,但对非基因组蛋白的可逆性尚未确立.
- 特定甲基化标记对p53功能及其与协活性剂相互作用的作用尚不清楚.
研究的目的:
- 为了调查素氨酸特异性去甲基酶LSD1是否去甲基化瘤抑制剂p53.
- 确定LSD1与p53相互作用对p53介导的转录激活和亡的影响.
- 阐明不同甲基化状态在p53.5的K370中的不同作用.
主要方法:
- 在体外和体内测试,以研究LSD1和p53.3之间的相互作用.
- 在K370.0处分析p53的甲基化和脱甲基化.
- 在LSD的存在下对p53的转录活性和亡促进的评估1.1.
- 研究p53与协同激活剂53BP1的关联.
主要成果:
- LSD1与p53相互作用,抑制其转录激活和促进亡的功能.
- 在体外,LSD1在K370中消除p53的单甲基化 (K370me1) 和二甲基化 (K370me2),而在体内更喜欢K370me2.
- K370me1抑制了p53的功能,而K370me2促进了p53与53BP1.1的关联.
- 通过阻止其与53BP1的相互作用,LSD1抑制了p53的功能.
结论:
- 通过氨酸甲基化和脱甲基化,p53被动态调节,类似于组织蛋白.
- p53在K370的甲基化状态决定了不同的监管结果.
- LSD1在通过脱甲基化调节p53活性方面发挥着关键作用,在癌症中提供了潜在的治疗点.
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