title: A new cellular stress response that triggers centriolar satellite reorganization and ciliogenesis.
abstract: 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.
authors.affiliation: Ubiquitin Signaling Group, Department of Disease Biology, The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Bine H
authors.initials: BH
authors.lastname: Villumsen
authors.forename: Jannie R
authors.initials: JR
authors.lastname: Danielsen
authors.forename: Lou
authors.initials: L
authors.lastname: Povlsen
authors.forename: Kathrine B
authors.initials: KB
authors.lastname: Sylvestersen
authors.forename: Andreas
authors.initials: A
authors.lastname: Merdes
authors.forename: Petra
authors.initials: P
authors.lastname: Beli
authors.forename: Yun-Gui
authors.identifier: 0000000228218541
authors.initials: YG
authors.lastname: Yang
authors.forename: Chunaram
authors.initials: C
authors.lastname: Choudhary
authors.forename: Michael L
authors.initials: ML
authors.lastname: Nielsen
authors.forename: Niels
authors.initials: N
authors.lastname: Mailand
authors.forename: Simon
authors.initials: S
authors.lastname: Bekker-Jensen
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D001324:Autoantigens / Q000378:metabolism*; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002502:Centrioles / Q000502:physiology*; D018385:Centrosome / Q000502:physiology; D002923:Cilia / Q000502:physiology*; D003598:Cytoskeletal Proteins; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D008868:Microtubule Proteins / Q000378:metabolism*; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation; D013312:Stress, Physiological; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D001324:Autoantigens; C578334:CEP131 protein, human; D018797:Cell Cycle Proteins; C493903:Cep290 protein, human; D003598:Cytoskeletal Proteins; D008868:Microtubule Proteins; D009363:Neoplasm Proteins; C086074:PCM1 protein, human; C513496:MIB1 ligase, human; D044767:Ubiquitin-Protein Ligases; D048308:Mitogen-Activated Protein Kinase 14; D048051:p38 Mitogen-Activated Protein Kinases