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

• Published in: Nature communications 2015-11, Vol.6 (1), p.10075-10075, Article 10075
• Main Authors: Tollenaere, Maxim A. X., Villumsen, Bine H., Blasius, Melanie, Nielsen, Julie C., Wagner, Sebastian A., Bartek, Jiri, Beli, Petra, Mailand, Niels, Bekker-Jensen, Simon
• Format: Article
• Language: English
• Subjects: 13/89; 14-3-3 Proteins - genetics; 14-3-3 Proteins - metabolism; 631/80/458/1733; 631/80/642; 631/80/86/2366; 82/58; 82/80; 96/106; 96/109; 96/34; 96/35; 96/95; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Centrioles - enzymology; Centrioles - genetics; Centrioles - metabolism; Humanities and Social Sciences; Humans; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Medicin och hälsovetenskap; Microtubule Proteins - genetics; Microtubule Proteins - metabolism; multidisciplinary; p38 Mitogen-Activated Protein Kinases - genetics; p38 Mitogen-Activated Protein Kinases - metabolism; Protein Binding; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Science; Science (multidisciplinary); Signal Transduction
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms10075

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. Centriolar satellites (CS) dynamically remodel in response to cellular stress. Here the authors describe a mechanism for stress-mediated remodelling, whereby CEP131 is phosphorylated downstream of p38, creating binding sites for 14-3-3 that lead to the sequestration of CEP131 in the cytoplasm and disassembly of CS.