NatD promotes lung cancer progression by preventing histone H4 serine phosphorylation to activate Slug expression.
NatD promotes lung cancer progression by preventing histone H4 serine phosphorylation to activate Slug expression.
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NatD 通过阻止组蛋白 H4 丝氨酸磷酸化激活 Slug 表达来促进肺癌进展
DOI：
10.1038/s41467-017-00988-5
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发表时间：
2017-10-13
影响因子：
16.6
通讯作者：
Zhao Q
中科院分区：
文献类型：
--
作者：
Ju J;Chen A;Deng Y;Liu M;Wang Y;Wang Y;Nie M;Wang C;Ding H;Yao B;Gui T;Li X;Xu Z;Ma C;Song Y;Kvansakul M;Zen K;Zhang CY;Luo C;Fang M;Huang DCS;Allis CD;Tan R;Zeng CK;Wei J;Zhao Q
N-α-乙酰转移酶D （NatD）介导组蛋白H4的N-α-末端乙酰化（nt -乙酰化），已知其参与细胞生长。在这里，我们报道了NatD在体外和体内促进肺癌细胞的迁移和侵袭能力。NatD的缺失通过直接抑制转录因子Slug的表达来抑制肺癌细胞上皮-间质转化（EMT），而转录因子Slug是EMT的关键调节因子。我们发现组蛋白H4的nt -乙酰化可拮抗组蛋白H4丝氨酸1磷酸化（H4S1ph），而组蛋白H4的nt -乙酰化下调可促进肺癌细胞中CK2α与组蛋白H4的结合，导致H4S1ph升高和表观遗传重编程，从而抑制Slug转录，从而抑制EMT。重要的是，NatD在原发性人肺癌组织中普遍上调，其表达水平与Slug表达、侵袭性增强和不良临床结果相关。这些发现表明，NatD是肺癌进展过程中细胞侵袭的重要表观遗传调节剂。NatD是一种乙酰转移酶，负责组蛋白H4和H2A的N-α-末端乙酰化，并与细胞生长有关。作者发现，natd介导的组蛋白H4丝氨酸1的乙酰化与CK2α在相同残基上的磷酸化相互竞争，从而导致Slug和肿瘤进展的上调。
N-α-acetyltransferase D (NatD) mediates N-α-terminal acetylation (Nt-acetylation) of histone H4 known to be involved in cell growth. Here we report that NatD promotes the migratory and invasive capabilities of lung cancer cells in vitro and in vivo. Depletion of NatD suppresses the epithelial-to-mesenchymal transition (EMT) of lung cancer cells by directly repressing the expression of transcription factor Slug, a key regulator of EMT. We found that Nt-acetylation of histone H4 antagonizes histone H4 serine 1 phosphorylation (H4S1ph), and that downregulation of Nt-acetylation of histone H4 facilitates CK2α binding to histone H4 in lung cancer cells, resulting in increased H4S1ph and epigenetic reprogramming to suppress Slug transcription to inhibit EMT. Importantly, NatD is commonly upregulated in primary human lung cancer tissues where its expression level correlates with Slug expression, enhanced invasiveness, and poor clinical outcomes. These findings indicate that NatD is a crucial epigenetic modulator of cell invasion during lung cancer progression. NatD is an acetyltransferase responsible for N-α-terminal acetylation of the histone H4 and H2A and has been linked to cell growth. Here the authors show that NatD-mediated acetylation of histone H4 serine 1 competes with the phosphorylation by CK2α at the same residue thus leading to the upregulation of Slug and tumor progression.
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影响因子：
16.8
作者：
Iwase, Shigeki;Xiang, Bin;Ghosh, Sharmistha;Ren, Ting;Lewis, Peter W.;Cochrane, Jesse C.;Allis, C. David;Picketts, David J.;Patel, Dinshaw J.;Li, Haitao;Shi, Yang
通讯作者：
Shi, Yang
遗传变异对中国人群血脂参数和血脂异常的影响
影响因子：
6.5
作者：
Liu, Yun;Zhou, Daizhan;He, Lin
通讯作者：
He, Lin
影响因子：
64.8
作者：
Fischer KR;Durrans A;Lee S;Sheng J;Li F;Wong ST;Choi H;El Rayes T;Ryu S;Troeger J;Schwabe RF;Vahdat LT;Altorki NK;Mittal V;Gao D
通讯作者：
Gao D
影响因子：
9.8
作者：
Forte GM;Pool MR;Stirling CJ
通讯作者：
Stirling CJ
影响因子：
5.6
作者：
Ermakova, I;Boldyreff, B;Niefind, K
通讯作者：
Niefind, K