VprBP has intrinsic kinase activity targeting histone H2A and represses gene transcription.
VprBP has intrinsic kinase activity targeting histone H2A and represses gene transcription.
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DOI：
10.1016/j.molcel.2013.09.017
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发表时间：
2013-11-07
期刊：
影响因子：
16
通讯作者：
An, Woojin
中科院分区：
文献类型：
--
作者：
Kim, Kyunghwan;Kim, Jin-Man;Kim, Joong-Sun;Choi, Jongkyu;Lee, Yong Suk;Neamati, Nouri;Song, Jin Sook;Heo, Kyu;An, Woojin
组蛋白修饰在基因表达和染色质组织的调控中起着重要的作用。VprBP与转录沉默的染色质形成和细胞周期调控有关，但这种作用的分子基础尚不清楚。在这里，我们报告说，VprBP具有内在的蛋白激酶活性，并能够磷酸化组蛋白H2A的苏氨酸120（H2AT120 p）在核小体的情况下。VprBP定位于大量的肿瘤抑制基因，并以依赖于其对H2AT120的激酶活性的方式阻断其转录。VprBP介导的H2AT120 p的功能意义进一步强调了RNAi敲除和VprBP的小分子抑制重新激活生长调节基因并阻碍肿瘤生长的事实。我们的研究结果建立了VprBP作为一个主要的激酶负责H2AT120 p在癌细胞中，并表明，VprBP抑制可能是一个新的策略，为发展抗癌治疗。
Histone modifications play important roles in the regulation of gene expression and chromatin organization. VprBP has been implicated in transcriptionally silent chromatin formation and cell cycle regulation, but the molecular basis underlying such effects remains unclear. Here we report that VprBP possesses an intrinsic protein kinase activity and is capable of phosphorylating histone H2A on threonine 120 (H2AT120p) in a nucleosomal context. VprBP is localized to a large set of tumor suppressor genes and blocks their transcription, in a manner that is dependent on its kinase activity toward H2AT120. The functional significance of VprBP-mediated H2AT120p is further underscored by the fact that RNAi knockdown and small-molecule inhibition of VprBP reactivate growth regulatory genes and impede tumor growth. Our findings establish VprBP as a major kinase responsible for H2AT120p in cancer cells and suggest that VprBP inhibition could be a new strategy for the development of anticancer therapeutics.
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影响因子：
64.5
作者：
Li W;You L;Cooper J;Schiavon G;Pepe-Caprio A;Zhou L;Ishii R;Giovannini M;Hanemann CO;Long SB;Erdjument-Bromage H;Zhou P;Tempst P;Giancotti FG
通讯作者：
Giancotti FG
影响因子：
5.6
作者：
Lowary, PT;Widom, J
通讯作者：
Widom, J
影响因子：
5.3
作者：
McCall, Chad M.;de Marval, Paula L. Miliani;Xiong, Yue
通讯作者：
Xiong, Yue
影响因子：
64.5
作者：
Shimada, Midori;Niida, Hiroyuki;Nakanishi, Makoto
通讯作者：
Nakanishi, Makoto
DOI：
10.1073/pnas.0711310105
发表时间：
2008-04-29
影响因子：
11.1
作者：
Casas-Mollano, J. Armando;Jeong, Byeong-Ryool;Cerutti, Heriberto
通讯作者：
Cerutti, Heriberto