A new cellular stress response that triggers centriolar satellite reorganization and ciliogenesis
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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A new cellular stress response that triggers centriolar satellite reorganization and ciliogenesis. / Villumsen, Bine H; Danielsen, Jannie R; Povlsen, Lou; Sylvestersen, Kathrine B; Merdes, Andreas; Beli, Petra; Yang, Yun-Gui; Choudhary, Chuna Ram; Nielsen, Michael L; Mailand, Niels; Bekker-Jensen, Simon.
I: E M B O Journal, Bind 32, Nr. 23, 11.10.2013, s. 3029-3040.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - A new cellular stress response that triggers centriolar satellite reorganization and ciliogenesis
AU - Villumsen, Bine H
AU - Danielsen, Jannie R
AU - Povlsen, Lou
AU - Sylvestersen, Kathrine B
AU - Merdes, Andreas
AU - Beli, Petra
AU - Yang, Yun-Gui
AU - Choudhary, Chuna Ram
AU - Nielsen, Michael L
AU - Mailand, Niels
AU - Bekker-Jensen, Simon
PY - 2013/10/11
Y1 - 2013/10/11
N2 - 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.
AB - 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.
U2 - 10.1038/emboj.2013.223
DO - 10.1038/emboj.2013.223
M3 - Journal article
C2 - 24121310
VL - 32
SP - 3029
EP - 3040
JO - E M B O Journal
JF - E M B O Journal
SN - 0261-4189
IS - 23
ER -
ID: 57413093