2. Academic Validation
  3. p38- and MK2-dependent signalling promotes stress-induced centriolar satellite remodelling via 14-3-3-dependent sequestration of CEP131/AZI1

p38- and MK2-dependent signalling promotes stress-induced centriolar satellite remodelling via 14-3-3-dependent sequestration of CEP131/AZI1

  • Nat Commun. 2015 Nov 30;6:10075. doi: 10.1038/ncomms10075.
Maxim A X Tollenaere 1,  Bine H Villumsen 1,  Melanie Blasius 2,  Julie C Nielsen 1,  Sebastian A Wagner 3,  Jiri Bartek 2 4,  Petra Beli 5,  Niels Mailand 1,  Simon Bekker-Jensen 1
Affiliations

Affiliations

  • 1 Ubiquitin Signaling Group, Protein Signaling Program, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen DK-2200, Denmark.
  • 2 Danish Cancer Society Research Center, Strandboulevarden 49, Copenhagen DK-2100, Denmark.
  • 3 Department of Medicine, Hematology/Oncology, Goethe University Medical School, Theodor-Stern-Kai 7, Frankfurt DE-60590, Germany.
  • 4 Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm SE-17176, Sweden.
  • 5 Institute of Molecular Biology, Ackermannweg 4, Mainz DE-55128, Germany.
PMID: 26616734 DOI: 10.1038/ncomms10075
Abstract

Centriolar satellites (CS) are small granular structures that cluster in the vicinity of centrosomes. CS are highly susceptible to stress stimuli, triggering abrupt displacement of key CS factors. Here we discover a linear p38-MK2-14-3-3 signalling pathway that specifically targets CEP131 to trigger CS remodelling after cell stress. We identify CEP131 as a substrate of the p38 effector kinase MK2 and pinpoint S47 and S78 as critical MK2 phosphorylation sites in CEP131. Ultraviolet-induced phosphorylation of these residues generates direct binding sites for 14-3-3 proteins, which sequester CEP131 in the cytoplasm to block formation of new CS, thereby leading to rapid depletion of these structures. Mutating S47 and S78 in CEP131 is sufficient to abolish stress-induced CS reorganization, demonstrating that CEP131 is the key regulatory target of MK2 and 14-3-3 in these structures. Our findings reveal the molecular mechanism underlying dynamic CS remodelling to modulate centrosome functions on cell stress.

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