Plakophilin-1 Localizes to the Nucleus and Interacts with Single-Stranded DNA
Plakophilin-1 Localizes to the Nucleus and Interacts with Single-Stranded DNA
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DOI：
10.1038/jid.2010.191
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发表时间：
2010-11-01
影响因子：
6.5
通讯作者：
Wahl, James K., III
中科院分区：
文献类型：
--
作者：
Sobolik-Delmaire, Tammy;Reddy, Roopa;Wahl, James K., III
亲血小板蛋白（Pkp-1， -2和-3）包括一个含有犰狳重复蛋白的蛋白家族，最初被鉴定为桥粒斑块成分，其中它们将桥粒斑块与桥粒钙粘蛋白连接起来。除了它们在桥粒细胞-细胞粘附中的作用，Pkps也定位于细胞核，在那里它们执行未知的功能。在三种Pkps中，Pkp-1最容易在细胞核中检测到，它定位于核质。在A431细胞中，含有Pkp-1头结构域和Pkp-3犰狳重复结构域的Pkp嵌合体定位于细胞核，而含有Pkp-3头结构域和Pkp-1犰狳重复结构域的Pkp嵌合体定位于桥粒和细胞质。在培养细胞中，dna酶I对染色质的消化导致核Pkp-1的丢失，这表明Pkp-1与核成分特异性相关。此外，体外实验显示Pkps-1和-2的氨基末端头部结构域足以结合单链DNA。DNA损伤诱导Pkp-1蛋白部分重新分布到核仁，Pkp-1的缺失导致DNA损伤后存活率的增加。这些数据表明，除了介导桥粒组装外，Pkp核库还可以通过与DNA的相互作用影响细胞存活。
Plakophilins (Pkp-1, -2, and -3) comprise a family of armadillo repeat-containing proteins first identified as desmosomal plaque components, in which they link desmoplakin to the desmosomal cadherins. In addition to their role in desmosomal cell-cell adhesion, Pkps also localize to the nucleus, where they perform unknown functions. Of the three Pkps, Pkp-1 is most readily detected in the nucleus, where it is localized to the nucleoplasm. Pkp chimeras containing the Pkp-1 head domain and Pkp-3 armadillo repeat domain were localized to the nucleus in A431 cells, whereas Pkp chimeras containing the Pkp-3 head domain and Pkp-1 armadillo repeat domain localized to the desmosome and the cytosol. DNAse I digestion of chromatin in cultured cells results in loss of nuclear Pkp-1, suggesting that Pkp-1 associates specifically with nuclear components. In addition, in vitro assays revealed that the amino-terminal head domains of Pkps-1 and -2 were sufficient to bind single-stranded DNA. Induction of DNA damage induced a partial redistribution of Pkp-1 protein to the nucleolus, and depletion of Pkp-1 resulted in increased survival in response to DNA damage. These data suggest that in addition to mediating desmosome assembly, the nuclear pool of Pkp can influence cell survival by interactions with DNA.