The deubiquitinating enzyme CYLD controls apical docking of basal bodies in ciliated epithelial cells
The deubiquitinating enzyme CYLD controls apical docking of basal bodies in ciliated epithelial cells
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DOI：
10.1038/ncomms5585
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发表时间：
2014-08-01
影响因子：
16.6
通讯作者：
Tassin, Anne-Marie
中科院分区：
文献类型：
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作者：
Eguether, Thibaut;Ermolaeva, Maria A.;Tassin, Anne-Marie
CYLD是一种在家族性圆柱瘤病中突变的肿瘤抑制基因，这是一种导致皮肤附件肿瘤发展的遗传性疾病。它编码一种去泛素化酶，去除Lys 63或线性连接的泛素链。CYLD显示通过各种信号传导途径调节细胞增殖、细胞存活和炎症反应。在这里，我们表明，CYLD定位在中心体和基体通过与中心体蛋白CAP 350的相互作用，并证明CYLD必须在中心体和催化活性，以促进独立的NF-κ B的纤毛发生。在经工程改造以模拟圆柱瘤病患者中发现的最小截短的转基因小鼠中，CYLD与CAP 350的相互作用丧失，破坏CYLD中心体定位，这导致由于基体迁移和对接受损而导致纤毛形成缺陷。这些结果指出了一个未被发现的调节纤毛Lys 63泛素化，并提供了新的观点，CYLD的功能，应考虑在圆柱瘤病的背景下。
CYLD is a tumour suppressor gene mutated in familial cylindromatosis, a genetic disorder leading to the development of skin appendage tumours. It encodes a deubiquitinating enzyme that removes Lys63-or linear-linked ubiquitin chains. CYLD was shown to regulate cell proliferation, cell survival and inflammatory responses, through various signalling pathways. Here we show that CYLD localizes at centrosomes and basal bodies via interaction with the centrosomal protein CAP350 and demonstrate that CYLD must be both at the centrosome and catalytically active to promote ciliogenesis independently of NF-kB. In transgenic mice engineered to mimic the smallest truncation found in cylindromatosis patients, CYLD interaction with CAP350 is lost disrupting CYLD centrosome localization, which results in cilia formation defects due to impairment of basal body migration and docking. These results point to an undiscovered regulation of ciliogenesis by Lys63 ubiquitination and provide new perspectives regarding CYLD function that should be considered in the context of cylindromatosis.