Ubiquitination of Lysine 867 of the Human SETDB1 Protein Upregulates Its Histone H3 Lysine 9 (H3K9) Methyltransferase Activity.
Ubiquitination of Lysine 867 of the Human SETDB1 Protein Upregulates Its Histone H3 Lysine 9 (H3K9) Methyltransferase Activity.
复制标题
DOI：
10.1371/journal.pone.0165766
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Doi T
中科院分区：
文献类型：
--
作者：
Ishimoto K;Kawamata N;Uchihara Y;Okubo M;Fujimoto R;Gotoh E;Kakinouchi K;Mizohata E;Hino N;Okada Y;Mochizuki Y;Tanaka T;Hamakubo T;Sakai J;Kodama T;Inoue T;Tachibana K;Doi T
蛋白质的翻译后修饰(PTM)在调节蛋白质之间的相互作用、酶活性、亚细胞定位和蛋白质的稳定性方面起着至关重要的作用。SET结构域，分支1(SETDB1)是一种组蛋白甲基转移酶，它调节组蛋白H3在赖氨酸9(H3K9)上的甲基化、基因沉默和转录抑制。SETDB1的C末端区域是PTMS的关键部位，对其在哺乳动物和昆虫细胞中的酶活性是必不可少的。在这项研究中，我们旨在更准确地评估PTMS对SETDB1的H3K9甲基转移酶活性的影响。通过质谱分析，我们发现从昆虫细胞中提纯的人SETDB1的C-末端区域是泛素化的。我们还证明，人SETDB1赖氨酸867的泛素化是哺乳动物细胞充分发挥H3K9甲基转移酶活性所必需的。最后，我们证明了SETDB1泛素化通过甲基化H3K9来调节其靶基因丝氨酸肽酶抑制剂，分支E，成员1(SERPINE1)的表达。这些结果表明，SETDB1赖氨酸867位的泛素化通过激活其H3K9甲基转移酶活性来控制其目标基因的表达。
Posttranslational modifications (PTMs) of proteins play a crucial role in regulating protein-protein interactions, enzyme activity, subcellular localization, and stability of the protein. SET domain, bifurcated 1 (SETDB1) is a histone methyltransferase that regulates the methylation of histone H3 on lysine 9 (H3K9), gene silencing, and transcriptional repression. The C-terminal region of SETDB1 is a key site for PTMs, and is essential for its enzyme activity in mammalian and insect cells. In this study, we aimed to evaluate more precisely the effect of PTMs on the H3K9 methyltransferase activity of SETDB1. Using mass spectrometry analysis, we show that the C-terminal region of human SETDB1 purified from insect cells is ubiquitinated. We also demonstrate that the ubiquitination of lysine 867 of the human SETDB1 is necessary for full H3K9 methyltransferase activity in mammalian cells. Finally, we show that SETDB1 ubiquitination regulates the expression of its target gene, serpin peptidase inhibitor, clade E, member 1 (SERPINE1) by methylating H3K9. These results suggest that the ubiquitination of SETDB1 at lysine 867 controls the expression of its target gene by activating its H3K9 methyltransferase activity.
登录
查看更多内容
甲基-CPG结合结构域蛋白的比较研究。
影响因子：
4.4
作者：
Roloff, TC;Ropers, HH;Nuber, UA
通讯作者：
Nuber, UA
影响因子：
8
作者：
通讯作者：
--
影响因子：
4.8
作者：
Carro, S;Bergo, A;Landsberger, N
通讯作者：
Landsberger, N
影响因子：
3.8
作者：
Hashimoto H;Vertino PM;Cheng X
通讯作者：
Cheng X
影响因子：
4.1
作者：
Ishimoto, Kenji;Tachibana, Keisuke;Doi, Takefumi
通讯作者：
Doi, Takefumi