Departments of Biochemistry and Molecular Biology and Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
PLoS One. 2012;7(11):e50591. doi: 10.1371/journal.pone.0050591. Epub 2012 Nov 30.
Annexin A2 is an abundant cellular protein that is mainly localized in the cytoplasm and plasma membrane, however a small population has been found in the nucleus, suggesting a nuclear function for the protein. Annexin A2 possesses a nuclear export sequence (NES) and inhibition of the NES is sufficient to cause nuclear accumulation. Here we show that annexin A2 accumulates in the nucleus in response to genotoxic agents including gamma-radiation, UV radiation, etoposide and chromium VI and that this event is mediated by the nuclear export sequence of annexin A2. Nuclear accumulation of annexin A2 is blocked by the antioxidant agent N-acetyl cysteine (NAC) and stimulated by hydrogen peroxide (H₂O₂), suggesting that this is a reactive oxygen species dependent event. In response to genotoxic agents, cells depleted of annexin A2 show enhanced phospho-histone H2AX and p53 levels, increased numbers of p53-binding protein 1 nuclear foci and increased levels of nuclear 8-oxo-2'-deoxyguanine, suggesting that annexin A2 plays a role in protecting DNA from damage. This is the first report showing the nuclear translocation of annexin A2 in response to genotoxic agents and its role in mitigating DNA damage.
膜联蛋白 A2 是一种丰富的细胞蛋白，主要定位于细胞质和质膜，但一小部分存在于核内，表明该蛋白具有核功能。膜联蛋白 A2 具有核输出序列 (NES)，抑制 NES 足以导致核内积累。在这里，我们表明，膜联蛋白 A2 在受到包括γ射线、紫外线、依托泊苷和六价铬在内的遗传毒性剂的刺激下在核内积累，并且该事件是通过膜联蛋白 A2 的核输出序列介导的。抗氧化剂 N-乙酰半胱氨酸 (NAC) 阻断膜联蛋白 A2 的核积累，并刺激过氧化氢 (H₂O₂)，表明这是一个依赖活性氧的事件。在响应遗传毒性剂时，耗尽膜联蛋白 A2 的细胞显示出增强的磷酸组蛋白 H2AX 和 p53 水平、增加的 p53 结合蛋白 1 核焦点数量和增加的核 8-氧-2'-脱氧鸟嘌呤水平，表明膜联蛋白 A2 在保护 DNA 免受损伤方面发挥作用。这是第一个报道膜联蛋白 A2 响应遗传毒性剂发生核易位及其在减轻 DNA 损伤中的作用的报告。
