CYLD negatively regulates Hippo signaling by limiting Hpo phosphorylation in Drosophila
CYLD negatively regulates Hippo signaling by limiting Hpo phosphorylation in Drosophila
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CYLD 通过限制果蝇中的 Hpo 磷酸化来负调节 Hippo 信号传导
DOI：
10.1016/j.bbrc.2014.09.005
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发表时间：
2014-09-26
影响因子：
3.1
通讯作者：
Wu, Shian
中科院分区：
文献类型：
--
作者：
Chen, Yan;Wang, Zaizhu;Wu, Shian
柱状细胞瘤（CYLD）是一种去泛素酶和微管动力学调节剂，在炎症、免疫反应、细胞凋亡、有丝分裂、细胞迁移和肿瘤发生的调节中具有重要作用。尽管CYLD的生化和细胞功能已取得巨大进展，但其在动物发育中的作用仍然难以捉摸。在这项研究中，我们确定果蝇 CYLD (dCYLD) 是体内 Hippo 通路的负调节因子。 dCYLD 与细胞质中 Hippo 途径的核心成分 Hpo 结合并共定位，并通过限制其在 T195 的磷酸化来降低 Hpo 活性。我们还表明，dCYLD 限制 Hippo 信号转导，这通过降低磷酸化从而增加 Yki（Hippo 途径的关键下游效应子）的活性来证明。这些发现揭示了 dCYLD 作为 Hippo 通路的负调节因子，并为 dCYLD 在动物发育中的生理功能提供了新的见解。 (C) 2014 Elsevier Inc. 保留所有权利。
Cylindromatosis (CYLD), a deubiquitinase and regulator of microtubule dynamics, has important roles in the regulation of inflammation, immune response, apoptosis, mitosis, cell migration and tumorigenesis. Although great progress has been made in the biochemical and cellular functions of CYLD, its role in animal development remains elusive. In this study, we identified Drosophila CYLD (dCYLD) as a negative regulator of the Hippo pathway in vivo. dCYLD associates and colocalizes with Hpo, a core component of the Hippo pathway, in the cytoplasm, and decreases Hpo activity through limiting its phosphorylation at T195. We also showed that dCYLD limits Hippo signal transduction as evidenced by decreasing phosphorylation and thereby increasing activity of Yki, the key downstream effector of the Hippo pathway. These findings uncover dCYLD as a negative regulator of the Hippo pathway and provide new insights into the physiological function of dCYLD in animal development. (C) 2014 Elsevier Inc. All rights reserved.