2-HG Inhibits Necroptosis by Stimulating DNMT1-Dependent Hypermethylation of the RIP3 Promoter

Abstract

异柠檬酸脱氢酶IDH1第132位的突变高发于神经胶质瘤和急性髓性白血病等疾病中,突变型的IDH1可以产生一种新的代谢产物2-HG,已有研究证明,2-HG会抑制α-酮戊二酸依赖型的双加氧酶TET2的活性,这种抑制现象会导致IDH1突变细胞中DNA甲基化水平的上升。 然而,在本论文中,我们发现了一种新的2-HG调控细胞内DNA甲基化水平的方式——通过调节DNA甲基转移酶DNMT1。2-HG的处理会促进DNMT1与RIP3启动子区域的结合,导致RIP3启动子上DNA甲基化水平的提升及RIP3表达量的下调,最终抑制细胞坏死的发生。除此之外,在本论文中,我们还证明了2-HG对RIP3表达量和对细胞坏死...The mutation in isocitrate dehydrogenases 1 (IDH1) at R132 confers a new function to this enzyme, which can produce a new metabolite named 2-hydroxyglutarate (2-HG). It has been proved that 2-HG can inhibit the activity of α-KG-dependent ten eleven translocation dioxygenases (TET2) due to the similar structure between 2-HG and α-KG. And this kind of inhibition will lead to DNA hypermethylation in ...学位:理学硕士院系专业:生命科学学院_生物化学与分子生物学学号:2162014115256

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