Polycystin-1 and polycystin-2 regulate the cell cycle through the helix-loop-helix inhibitor ld2
Polycystin-1 and polycystin-2 regulate the cell cycle through the helix-loop-helix inhibitor ld2
复制标题
DOI：
10.1038/ncb1326
复制
发表时间：
2005-12-01
影响因子：
21.3
通讯作者：
Zhou, J
中科院分区：
文献类型：
--
作者：
Li, XG;Luo, Y;Zhou, J
常染色体显性遗传性多囊肾病（ADPKD）是最常见的遗传性肾病，其特征是进行性囊肿形成和最终肾功能丧失。细胞增殖增加是该疾病的一个关键特征。在这里，我们表明，ADPKD蛋白多囊蛋白-2（PC 2）调节细胞周期，通过直接与Id 2，一个成员的螺旋-环-螺旋（HLH）蛋白家族，已知调节细胞增殖和分化。Id 2表达抑制多囊蛋白-1（PC 1）或PC 2对细胞周期蛋白依赖性激酶抑制剂p21的诱导。PC 2-Id 2相互作用受PC 1依赖的PC 2磷酸化调节。增强的Id 2核定位在人类和小鼠囊性肾中可见。通过RNA干扰抑制Id 2表达可纠正PC 1突变细胞的过度增殖表型。我们认为Id 2在PC 1和PC 2介导的细胞周期调节中发挥着至关重要的作用。
Autosomal-dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and is characterized by progressive cyst formation and ultimate loss of renal function. Increased cell proliferation is a key feature of the disease. Here, we show that the ADPKD protein polycystin-2 (PC2) regulates the cell cycle through direct interaction with Id2, a member of the helix-loop-helix (HLH) protein family that is known to regulate cell proliferation and differentiation. Id2 expression suppresses the induction of a cyclin-dependent kinase inhibitor, p21, by either polycystin-1 (PC1) or PC2. The PC2-Id2 interaction is regulated by PC1-dependent phosphorylation of PC2. Enhanced Id2 nuclear localization is seen in human and mouse cystic kidneys. Inhibition of Id2 expression by RNA interference corrects the hyperproliferative phenotype of PC1 mutant cells. We propose that Id2 has a crucial role in cell-cycle regulation that is mediated by PC1 and PC2.