The cytoskeleton adaptor protein ankyrin-1 is upregulated by p53 following DNA damage and alters cell migration.
The cytoskeleton adaptor protein ankyrin-1 is upregulated by p53 following DNA damage and alters cell migration.
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DOI：
10.1038/cddis.2016.91
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发表时间：
2016-04-07
影响因子：
9
通讯作者：
Bushell M
中科院分区：
文献类型：
--
作者：
Hall AE;Lu WT;Godfrey JD;Antonov AV;Paicu C;Moxon S;Dalmay T;Wilczynska A;Muller PA;Bushell M
基因组的完整性是由一系列对细胞功能至关重要的监视和修复机制来维持的。肿瘤抑制蛋白p53是DNA损伤反应途径的主要组成部分，在维持细胞周期检查点中起着至关重要的作用。在这里，我们表明，一个microRNA，miR-486，和它的宿主基因锚蛋白-1（ANK 1）诱导p53后DNA损伤。引人注目的是，细胞骨架衔接蛋白锚蛋白-1诱导超过80倍的DNA损伤后。ANK 1在一系列细胞类型中响应于多种DNA损伤剂而上调。我们证明，miR-486- 5 p参与控制DNA损伤后的G1/S转换，而锚蛋白-1蛋白的诱导改变了肌动蛋白细胞骨架的结构，并在DNA损伤期间维持有限的细胞迁移。重要的是，我们发现ANK 1的高表达与癌症患者的生存率降低相关。因此，这些观察结果突出了ANK 1作为p53通路下游的重要效应子。
The integrity of the genome is maintained by a host of surveillance and repair mechanisms that are pivotal for cellular function. The tumour suppressor protein p53 is a major component of the DNA damage response pathway and plays a vital role in the maintenance of cell-cycle checkpoints. Here we show that a microRNA, miR-486, and its host gene ankyrin-1 (ANK1) are induced by p53 following DNA damage. Strikingly, the cytoskeleton adaptor protein ankyrin-1 was induced over 80-fold following DNA damage. ANK1 is upregulated in response to a variety of DNA damage agents in a range of cell types. We demonstrate that miR-486-5p is involved in controlling G1/S transition following DNA damage, whereas the induction of the ankyrin-1 protein alters the structure of the actin cytoskeleton and sustains limited cell migration during DNA damage. Importantly, we found that higher ANK1 expression correlates with decreased survival in cancer patients. Thus, these observations highlight ANK1 as an important effector downstream of the p53 pathway.