The ciliary protein cystin forms a regulatory complex with necdin to modulate Myc expression.
The ciliary protein cystin forms a regulatory complex with necdin to modulate Myc expression.
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DOI：
10.1371/journal.pone.0083062
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Guay-Woodford LM
中科院分区：
文献类型：
--
作者：
Wu M;Yang C;Tao B;Bu S;Guay-Woodford LM
Cystin 是一种新型纤毛相关蛋白，在 cpk 小鼠中被破坏，cpk 小鼠是一种典型的常染色体隐性多囊肾病 (ARPKD) 小鼠模型。有趣的是，Myc 基因的过度表达在 ARPKD 动物模型中很明显，并且被认为与肾囊性表型有关。使用酵母双杂交方法，发现生长抑制蛋白 necdin（已知可调节 Myc 表达）是胱氨酸的相互作用伙伴。缺失图谱表明胱氨酸的 C 末端和 necdin 的两个末端是它们相互作用所必需的。推测这两种蛋白可能具有调节基因表达的功能，我们开发了一种荧光素酶报告基因检测，并观察到 necdin 强烈激活 Myc P1 启动子，而胱氨酸则较为温和。有趣的是，当共转染胱氨酸时，necdin 效应显着消除。染色质免疫沉淀和电泳迁移率变动分析揭示了 necdin 和胱氨酸以及 Myc P1 启动子以及这些蛋白质之间的物理相互作用。数据表明这些蛋白质可能在调节复合体中发挥作用。因此，我们推测 cpk 肾脏中 Myc 的过度表达是由胱氨酸-necdin 调节复合物和 c-Myc 的失调引起的，反过来，导致 cpk 小鼠的囊肿发生。
Cystin is a novel cilia-associated protein that is disrupted in the cpk mouse, a well-characterized mouse model of autosomal recessive polycystic kidney disease (ARPKD). Interestingly, overexpression of the Myc gene is evident in animal models of ARPKD and is thought to contribute to the renal cystic phenotype. Using a yeast two-hybrid approach, the growth suppressor protein necdin, known to modulate Myc expression, was found as an interacting partner of cystin. Deletion mapping demonstrated that the C-terminus of cystin and both termini of necdin are required for their mutual interaction. Speculating that these two proteins may function to regulate gene expression, we developed a luciferase reporter assay and observed that necdin strongly activated the Myc P1 promoter, and cystin did so more modestly. Interestingly, the necdin effect was significantly abrogated when cystin was co-transfected. Chromatin immunoprecipitation and electrophoretic mobility shift assays revealed a physical interaction with both necdin and cystin and the Myc P1 promoter, as well as between these proteins. The data suggest that these proteins likely function in a regulatory complex. Thus, we speculate that Myc overexpression in the cpk kidney results from the dysregulation of the cystin-necdin regulatory complex and c-Myc, in turn, contributes to cystogenesis in the cpk mouse.
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影响因子：
3
作者：
Goilav, Beatrice;Satlin, Lisa M.;Wilson, Patricia D.
通讯作者：
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DOI：
10.2215/cjn.05611207
发表时间：
2008-07-01
影响因子：
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