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

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

doi:10.1038/emboj.2013.223

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

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

73 Citations (Scopus)

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.

Original language	English
Journal	E M B O Journal
Volume	32
Issue number	23
Pages (from-to)	3029-3040
ISSN	0261-4189
DOIs	https://doi.org/10.1038/emboj.2013.223
Publication status	Published - 27 Nov 2013

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@article{1ce122b469b740b4ad39553022a8b317,

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.",

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

year = "2013",

month = nov,

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doi = "10.1038/emboj.2013.223",

language = "English",

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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 - 2013/11/27

Y1 - 2013/11/27

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

SN - 0261-4189

VL - 32

SP - 3029

EP - 3040

JO - E M B O Journal

JF - E M B O Journal

IS - 23

ER -

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

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