A new cellular stress response that triggers centriolar satellite reorganization and ciliogenesis

Research output: Contribution to journalJournal articleResearchpeer-review

Bine H Villumsen, Jannie R Danielsen, Lou Povlsen, Kathrine B Sylvestersen, Andreas Merdes, Petra Beli, Yun-Gui Yang, Chuna Ram Choudhary, Michael L Nielsen, Niels Mailand, Simon Bekker-Jensen

Centriolar satellites are small, granular structures that cluster around centrosomes, but whose biological function and regulation are poorly understood. We show that centriolar satellites undergo striking reorganization in response to cellular stresses such as UV radiation, heat shock, and transcription blocks, invoking acute and selective displacement of the factors AZI1/CEP131, PCM1, and CEP290 from this compartment triggered by activation of the stress-responsive kinase p38/MAPK14. We demonstrate that the E3 ubiquitin ligase MIB1 is a new component of centriolar satellites, which interacts with and ubiquitylates AZI1 and PCM1 and suppresses primary cilium formation. In response to cell stress, MIB1 is abruptly inactivated in a p38-independent manner, leading to loss of AZI1, PCM1, and CEP290 ubiquitylation and concomitant stimulation of ciliogenesis, even in proliferating cells. Collectively, our findings uncover a new two-pronged signalling response, which by coupling p38-dependent phosphorylation with MIB1-catalysed ubiquitylation of ciliogenesis-promoting factors plays an important role in controlling centriolar satellite status and key centrosomal functions in a cell stress-regulated manner.
Original languageEnglish
JournalE M B O Journal
Volume32
Issue number23
Pages (from-to)3029-3040
ISSN0261-4189
DOIs
Publication statusPublished - 11 Oct 2013

ID: 57413093