*3.3. CYLD and MIB1*

Cylindromatosis (CYLD) is a member of the USP family of proteins and is expressed in centriolar satellites [148]. CYLD stimulates ciliogenesis by stabilizing centrosomal protein 70 (CEP70) and pericentriolar material 1 (PCM1) [132,133]. Stabilization of PCM1 by CYLD is mediated by deubiquitination of mindbomb E3 ubiquitin protein ligase 1 (MIB1), which is activated by ubiquitination on lysine 63 [133]. Lysine 63-ubiquitinated MIB1 then ubiquitinates PCM1 and stimulates its degradation in proteasomes. CYLD antagonizes the degradation of PCM1 by suppressing the activity of MIB1. MIB1 also ubiquitinates KIAA0586, a centrosomal protein also known as Talpid3, thereby stimulating its degradation and inhibiting ciliogenesis [136]. These findings sugges<sup>t</sup> that CYLD and MIB1 positively and negatively, respectively, regulate ciliogenesis. Loss-of-function mutations in CYLD are associated with familial cylindromatosis, a condition involving multiple skin tumors [135]. MIB1 is oncogenic in upper urinary tract urothelial carcinomas [137]. Knockout or knockdown of CYLD in mice and zebrafish show phenotypes related to ciliopathy [134,149]. PCM1 and KIAA0586, both substrates of MIB1, are also associated with ciliopathies [149,150].
