CYLD is a deubiquitylase with tumor suppressor functions, first identified in patients with familial cylindromatosis. Despite many molecular mechanisms in which a function of CYLD was reported, affected patients only develop skin appendage tumors, and their precise pathogenesis remains enigmatic. To elucidate how CYLD contributes to tumor formation, we aimed to identify molecular partners in keratinocytes. By using yeast two-hybrid, coprecipitation, and proximity ligation experiments, we identified CENPV as a CYLD-interacting partner. CENPV, a constituent of mitotic chromosomes associating with cytoplasmic microtubules, interacts with CYLD through the region between the third cytoskeleton-associated protein-glycine domain and the active site. CENPV is deubiquitylated by CYLD and localizes in interphase to primary cilia where it increases the ciliary levels of acetylated α-tubulin. CENPV is overexpressed in basal cell carcinoma. Our results support the notion that centromeric proteins have functions in ciliogenesis.

中文翻译：

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CENPV是一种调节CYLD相互作用的分子，调节睫状乙酰化α-微管蛋白。

CYLD是一种具有肿瘤抑制功能的去泛素化酶，最早是在家族性圆柱状增生病患者中发现的。尽管有许多分子机制报道了CYLD的功能，但受影响的患者仅会出现皮肤附件肿瘤，其确切的发病机理仍是难以捉摸的。为了阐明CYLD如何促进肿瘤形成，我们旨在鉴定角质形成细胞中的分子伴侣。通过使用酵母双杂交，共沉淀和邻近连接实验，我们确定了CENPV为CYLD相互作用的伙伴。CENPV是与细胞质微管相关的有丝分裂染色体的组成部分，通过第三个与细胞骨架相关的蛋白质-甘氨酸结构域和活性位点之间的区域与CYLD相互作用。CENPV被CYLD去泛素化，并在相间定位于原发纤毛，在纤毛中增加了乙酰化α-微管蛋白的纤毛水平。CENPV在基底细胞癌中过表达。我们的研究结果支持着丝粒蛋白在纤毛发生中具有功能的观点。