CENPV Is a CYLD-Interacting Molecule Regulating Ciliary Acetylated α-Tubulin

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.