A new cellular stress response that triggers centriolar satellite reorganization and ciliogenesis.
Bine H VillumsenJannie R DanielsenLou PovlsenKathrine B SylvestersenAndreas MerdesPetra BeliYun-Gui YangChunaram ChoudharyMichael L NielsenNiels MailandSimon Bekker-JensenPublished in: The EMBO journal (2013)
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.
Keyphrases
- heat shock
- single cell
- cell therapy
- heat stress
- induced apoptosis
- stress induced
- transcription factor
- liver failure
- protein kinase
- high resolution
- cell cycle arrest
- heat shock protein
- endoplasmic reticulum stress
- oxidative stress
- cell death
- radiation therapy
- mesenchymal stem cells
- cell proliferation
- room temperature
- tyrosine kinase
- extracorporeal membrane oxygenation
- drug delivery