Depletion of PKD1 by an antisense oligodeoxynucleotide induces premature G1/S-phase transition
Depletion of PKD1 by an antisense oligodeoxynucleotide induces premature G1/S-phase transition
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DOI：
10.1038/sj.ejhg.5201136
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发表时间：
2004-06-01
影响因子：
5.2
通讯作者：
Kang, SM
中科院分区：
文献类型：
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作者：
Kim, H;Bae, Y;Kang, SM
常染色体显性遗传性多囊肾病（ADPKD）的特征是上皮细胞生长和囊液内流。多囊肾病基因PKD 1的14 kb mRNA编码多囊蛋白-1蛋白，其功能尚不清楚。在本研究中，我们观察到多囊蛋白-1定位于293细胞的上皮细胞-细胞接触。我们发现，通过溴脱氧尿苷（BrdU）掺入实验和蛋白质印迹分析的S期特异性细胞周期蛋白，多囊蛋白-1的耗竭导致细胞增殖率增加，并引起过早的G1/S期转变。此外，我们发现，多囊蛋白-1的耗竭减少了紫外线照射的293细胞中p53的量，表明多囊蛋白-1作为G1检查点的调节剂，其控制进入S期并防止受损DNA的复制。我们的研究结果可能会提供一个深入了解ADPKD囊肿的形成和发展。
Autosomal dominant polycystic kidney disease ( ADPKD) is characterized by the growth of epithelial cells and the influx of cyst fluid. The 14-kb mRNA of the polycystic kidney disease gene, PKD1, encodes the polycystin-1 protein, whose function remains unknown. In this study, we observed that polycystin-1 localized in epithelial cell - cell contacts of 293 cells. We found, by bromodeoxyuridine ( BrdU) incorporation experiments and Western blot analysis of S-phase-specific cyclins, that the depletion of polycystin-1 led to an increased cell proliferation rate and caused a premature G1/S-phase transition. In addition, we showed that the depletion of polycystin-1 reduced the amount of p53 in 293 cells irradiated by UV light, suggesting that polycystin-1 acts as a regulator of G1 checkpoint, which controls entry into the S phase and prevents the replication of damaged DNA. Our results might provide an insight into the formation and progression of ADPKD cysts.