The PHD finger of the chromatin-associated protein ING2 functions as a nuclear phosphoinositide receptor
The PHD finger of the chromatin-associated protein ING2 functions as a nuclear phosphoinositide receptor
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DOI：
10.1016/s0092-8674(03)00480-x
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发表时间：
2003-07-11
期刊：
影响因子：
64.5
通讯作者：
Yuan, JY
中科院分区：
文献类型：
--
作者：
Gozani, O;Karuman, P;Yuan, JY
磷酸肌醇（PtdInsPs）在细胞质信号转导途径中起着重要作用。然而，它们在细胞核中的功能尚不清楚，因为PtdInsPs的特异性核受体尚未鉴定。在这里，我们表明，ING 2，一个候选的肿瘤抑制蛋白，是一个核PtdInsP受体。ING 2含有一个植物同源结构域（PHD）指，这是许多染色质调节蛋白共有的基序。我们发现ING 2的PHD指和其他不同的核蛋白在体外与PtdInsP结合，包括罕见的PtdInsP种类，磷脂酰肌醇5-磷酸（PtdIns（5）P）。此外，我们证明ING 2 PHD指与PtdIns（5）P在体内相互作用，并提供证据表明这种相互作用调节ING 2激活p53和p53依赖性凋亡途径的能力。总之，我们的数据确定PHD手指作为一个磷酸肌醇结合模块和核PtdInsP受体，并建议PHD-磷酸肌醇相互作用直接调节核反应的DNA损伤。
Phosphoinositides (PtdInsPs) play critical roles in cytoplasmic signal transduction pathways. However, their functions in the nucleus are unclear, as specific nuclear receptors for PtdInsPs have not been identified. Here, we show that ING2, a candidate tumor suppressor protein, is a nuclear PtdInsP receptor. ING2 contains a plant homeodomain (PHD) finger, a motif common to many chromatin-regulatory proteins. We find that the PHD fingers of ING2 and other diverse nuclear proteins bind in vitro to PtdInsPs, including the rare PtdInsP species, phosphatidylinositol 5-phosphate (PtdIns(5)P). Further, we demonstrate that the ING2 PHD finger interacts with PtdIns(5)P in vivo and provide evidence that this interaction regulates the ability of ING2 to activate p53 and p53-dependent apoptotic pathways. Together, our data identify the PHD finger as a phosphoinositide binding module and a nuclear PtdInsP receptor, and suggest that PHD-phosphoinositide interactions directly regulate nuclear responses to DNA damage.