A potential role for protein palmitoylation and zDHHC16 in DNA damage response.
A potential role for protein palmitoylation and zDHHC16 in DNA damage response.
复制标题
蛋白质棕榈酰化和 zDHHC16 在 DNA 损伤反应中的潜在作用
DOI：
10.1186/s12867-016-0065-9
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发表时间：
2016-05-10
影响因子：
--
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Cao N;Li JK;Rao YQ;Liu H;Wu J;Li B;Zhao P;Zeng L;Li J
细胞对DNA损伤的反应是通过激活磷脂酰肌醇-3激酶相关激酶、p53和其他途径来促进细胞周期阻滞、细胞凋亡和/或DNA修复。在这里，我们报道了蛋白棕榈酰化，一种由带有锌指和Asp-His-His-Cys结构域（zDHHC）的蛋白酰基转移酶进行的修饰，是适当的DNA损伤反应所必需的。结果抑制蛋白棕榈酰化可抑制DNA损伤诱导的Atm激活、p53的诱导和激活、细胞周期阻滞在G2/M期和DNA损伤灶的组装/拆卸。此外，敲除zDHHC16（一种棕榈酰转移酶基因，被鉴定为参与DNA损伤反应的c-Abl的相互作用蛋白，c-Abl是一种非受体酪氨酸激酶，参与DNA损伤反应），再现了由于抑制蛋白棕榈酰化而产生的DNA损伤反应中的大多数缺陷。结论研究结果揭示了棕榈酰化蛋白和棕榈酰转移酶zDHHC16在DNA损伤早期反应和调控Atm活化中起关键作用。
BackgroundCells respond to DNA damage by activating the phosphatidylinositol-3 kinase-related kinases, p53 and other pathways to promote cell cycle arrest, apoptosis, and/or DNA repair. Here we report that protein palmitoylation, a modification carried out by protein acyltransferases with zinc-finger and Asp-His-His-Cys domains (zDHHC), is required for proper DNA damage responses.ResultsInhibition of protein palmitoylation compromised DNA damage-induced activation of Atm, induction and activation of p53, cell cycle arrest at G2/M phase, and DNA damage foci assembly/disassembly in primary mouse embryonic fibroblasts. Furthermore, knockout of zDHHC16, a palmitoyltransferase gene identified as an interacting protein for c-Abl, a non-receptor tyrosine kinase involved in DNA damage response, reproduced most of the defects in DNA damage responses produced by the inhibition of protein palmitoylation.ConclusionsOur results revealed critical roles for protein palmitoylation and palmitoyltransferase zDHHC16 in early stages of DNA damage responses and in the regulation of Atm activation.