The inherited blindness associated protein AIPL1 interacts with the cell cycle regulator protein NUB1
The inherited blindness associated protein AIPL1 interacts with the cell cycle regulator protein NUB1
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DOI：
10.1093/hmg/11.22.2723
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发表时间：
2002-10-15
影响因子：
3.5
通讯作者：
Sohocki, MM
中科院分区：
文献类型：
--
作者：
Akey, DT;Zhu, XM;Sohocki, MM
芳烃受体相互作用蛋白样1 （AlPL1）基因突变已在Leber先天性黑朦（LCA）患者中发现，LCA是一种严重的早发性视网膜变性。为了确定AlPL1的正常功能并更好地了解该基因突变如何导致疾病，我们进行了酵母双杂交筛选，以鉴定视网膜中AlPL1相互作用蛋白。其中一个鉴定的相互作用蛋白对应于NUB1 (NEDD8 Ultimate Buster 1)，该蛋白被认为通过下调NEDD8的表达来控制许多生物事件，特别是细胞周期进程。在Y79视网膜母细胞瘤细胞中的共免疫沉淀研究证实了AlPL1-NUB1相互作用，表明这种相互作用发生在与视网膜祖细胞具有许多共同特征的细胞内。此外，我们检查了AlPL1蛋白在发育和成人视网膜中的定位，发现AlPL1存在于人类视网膜的发育感光层和成人视网膜的感光层中。与AlPL1类似，NUB1也在发育和成人视网膜中表达。因此，在AlPL1突变的LCA患者中看到的早发性视网膜变性可能是由于光感受器成熟过程中细胞周期进程的调节缺陷所致。这些数据提出了一种可能性，即AlPL1在发育和/或分化后的生存过程中对适当的光感受器形成很重要。
Mutations in the aryl hydrocarbon receptor-interacting protein-like 1 (AlPL1) gene have been found in patients with Leber congenital amaurosis (LCA), a severe, early-onset form of retinal degeneration. To determine the normal function of AlPL1 and to better understand how mutations in this gene cause disease, we performed a yeast two-hybrid screen to identify AlPL1-interacting proteins in the retina. One of the identified interacting proteins corresponds to NUB1 (NEDD8 Ultimate Buster 1), which is thought to control many biological events, especially cell cycle progression, by downregulating NEDD8 expression. The AlPL1-NUB1 interaction was verified by co-immunoprecipitation studies in Y79 retinoblastoma cells, demonstrating that this interaction occurs within cells that share a number of features with retinal progenitor cells. Furthermore, we examined the localization of the AlPL1 protein within developing and adult retinas, and found that AlPL1 is present in the developing photoreceptor layer of the human retina and within the photoreceptors of the adult retina. Similar to AlPL1, NUB1 is also expressed in the developing and adult retina. Therefore, it is possible that the early-onset form of retinal degeneration seen in LCA patients with AlPL1 mutations may be due to a defect in the regulation of cell cycle progression during photoreceptor maturation. These data raise the possibility that AlPL1 is important for appropriate photoreceptor formation during development and/or survival following differentiation.