CYLD Regulates Centriolar Satellites Proteostasis by Counteracting the E3 Ligase MIB1

Abstract

Summary: The tumor suppressor CYLD is a deubiquitinating enzyme that removes non-degradative ubiquitin linkages bound to a variety of signal transduction adaptors. CYLD participates in the formation of primary cilia, a microtubule-based structure that protrudes from the cell body to act as a “sensing antenna.” Yet, how exactly CYLD regulates ciliogenesis is not fully understood. Here, we conducted an unbiased proteomic screen of CYLD binding partners and identified components of the centriolar satellites. These small granular structures, tethered to the scaffold protein pericentriolar matrix protein 1 (PCM1), gravitate toward the centrosome and orchestrate ciliogenesis. CYLD knockdown promotes PCM1 degradation and the subsequent dismantling of the centriolar satellites. We found that CYLD marshals the centriolar satellites by deubiquitinating and preventing the E3 ligase Mindbomb 1 (MIB1) from marking PCM1 for proteasomal degradation. These results link CYLD to the regulation of centriolar satellites proteostasis and provide insight into how reversible ubiquitination finely tunes ciliogenesis. : Douanne et al. find that a subset of the deubiquitinating enzyme CYLD is part of the centriolar satellites and controls their proteostasis, therefore allowing the formation of primary cilia. They show that CYLD removes ubiquitin from the E3 ligase MIB1 and prevents MIB1-mediated dismantlement of centriolar satellites. Keywords: CYLD, centriolar satellites, PCM1, proteostasis, MIB1, ciliogenesis, ubiquitin