Nek1 and TAZ interact to maintain normal levels of polycystin 2.
Nek1 and TAZ interact to maintain normal levels of polycystin 2.
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DOI：
10.1681/asn.2010090992
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发表时间：
2011-05
期刊：
影响因子：
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通讯作者：
H. Yim;C. Sung;J. You;Yu Tian;T. Benjamin
中科院分区：
文献类型：
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作者：
H. Yim;C. Sung;J. You;Yu Tian;T. Benjamin
小鼠的多囊肾病（PKD）可由参与纤毛发生的Nek激酶缺陷引起。PKD也可以由蛋白TAZ的损失引起，TAZ是E3泛素连接酶复合物中的衔接蛋白，其靶向纤毛蛋白多囊蛋白2（PC2）进行降解，但Nek和TAZ是否有助于相同的生化途径尚不清楚。在这里，我们报告说，nimA相关的蛋白激酶Nek 1磷酸化TAZ在一个网站的泛素化和蛋白酶体降解的PC 2。Nek 1的缺失导致TAZ磷酸化不足，从而促进PC 2的异常积累。此外，TAZ靶向Nek1进行降解。这些数据表明，TAZ和Nek 1构成了一个负反馈环，通过磷酸化和泛素化连接，Nek 1和TAZ的相互作用维持PC2在适当的纤毛发生所需的水平。
Polycystic kidney disease (PKD) in mice can arise from defects in Nek kinases, which participate in ciliogenesis. PKD can also arise from loss of the protein TAZ, an adaptor protein in the E3 ubiquitin ligase complex that targets the ciliary protein polycystin 2 (PC2) for degradation, but whether Nek and TAZ contribute to the same biochemical pathway is unknown. Here, we report that the nimA-related protein kinase Nek1 phosphorylates TAZ at a site essential for the ubiquitination and proteasomal degradation of PC2. Loss of Nek1 leads to underphosphorylation of TAZ, thereby promoting the abnormal accumulation of PC2. Furthermore, TAZ targets Nek1 for degradation. These data suggest that TAZ and Nek1 constitute a negative feedback loop linked through phosphorylation and ubiquitination and that the interaction of Nek1 and TAZ maintain PC2 at the level needed for proper ciliogenesis.