State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, PR China.
State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300071, PR China.
Biochem Biophys Res Commun. 2014 Sep 26;452(3):808-12. doi: 10.1016/j.bbrc.2014.09.005. Epub 2014 Sep 6.
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.
圆柱瘤病（CYLD）是一种去泛素化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。尽管在 CYLD 的生化和细胞功能方面已经取得了很大进展，但它在动物发育中的作用仍然难以捉摸。在这项研究中，我们鉴定了果蝇 CYLD（dCYLD）作为体内 Hippo 通路的负调节剂。dCYLD 与 Hippo 通路的核心组成部分 Hpo 在细胞质中结合并共定位，并通过限制其在 T195 处的磷酸化来降低 Hpo 的活性。我们还表明，dCYLD 限制 Hippo 信号转导，这可以通过减少磷酸化并从而增加 Hippo 通路的关键下游效应物 Yki 的活性来证明。这些发现揭示了 dCYLD 是 Hippo 通路的负调节剂，并为 dCYLD 在动物发育中的生理功能提供了新的见解。
