Regulation of Ripply1 expression in MDCK organoids.
Regulation of Ripply1 expression in MDCK organoids.
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MDCK 类器官中 Ripply1 表达的调节。
DOI：
10.1016/j.bbrc.2015.10.099
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发表时间：
2015
影响因子：
3.1
通讯作者：
E. Kiyokawa
中科院分区：
文献类型：
--
作者：
H. Yoshizaki;Y. Kuwajima;H. Minato;E. Kiyokawa
上皮器官是由极化良好的单层上皮细胞构成的，必须保持它们的形态才能正常发挥作用。为了检测在成囊后期特异表达的与维持成熟包囊形态相关的基因，我们用微阵列技术比较了马丁达比犬肾(MDCK)成囊早期和成囊晚期的mRNA表达。我们发现，其中一个候选基因Ripply1在后期表达较高，在早期也有短暂的高表达。尽管Ripply1的蛋白表达表现出相似的动力学，但Ripply1的缺失对类器官的生长只有轻微的影响。出乎意料的是，我们发现Ripply1蛋白被蛋白酶体系统降解。突变分析表明，Ripply1不是直接泛素化的，而是只有在与转录抑制因子Split(TLE)1的转导素样增强子结合后才被降解。Ripply1在细胞核中被降解，这种降解在有丝分裂期间被抑制。这些数据首次表明Ripply1的表达在蛋白质水平上受到调控。
Epithelial organs are made of a well-polarized monolayer of epithelial cells, and their morphology must be maintained for their proper function. To examine the genes that are specifically expressed in the late stages of cystogenesis and are involved in maintaining the morphology of the mature cysts, we performed a microarray analysis comparing the mRNA expression between the early and late stages of Madin–Darby Canine Kidney (MDCK) cystogenesis. We found that one of the gene candidates, Ripply1, was expressed higher in the late stages, and its expression was also transiently much higher in the early stages. Although the protein expression showed similar kinetics, depletion of Ripply1 had only a slight effect on organoid growth. Unexpectedly, we found that the Ripply1 protein is degraded by the proteasome system. Mutant analysis suggests that Ripply1 is not ubiquitinated directly, but rather is degraded only after binding to Transducin-like Enhancer of Split (TLE)1, a transcriptional repressor. Ripply1 is degraded in the nucleus, and this degradation is inhibited during the mitosis. These data indicate for the first time that Ripply1 expression is regulated at the protein level.
影响因子：
2.7
作者：
Pollack, AL;Runyan, RB;Mostov, KE
通讯作者：
Mostov, KE