Centriolar distal appendages activate the centrosome-PIDDosome-p53 signalling axis via ANKRD26

Burigotto, Matteo and Mattivi, Alessia and Migliorati, Daniele and Magnani, Giovanni and Valentini, Chiara and Roccuzzo, Michela and Offterdinger, Martin and Pizzato, Massimo and Schmidt, Alexander and Villunger, Andreas and Maffini, Stefano and Fava, Luca L.. (2021) Centriolar distal appendages activate the centrosome-PIDDosome-p53 signalling axis via ANKRD26. The EMBO journal, 40 (4). e104844.

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Official URL: https://edoc.unibas.ch/87230/

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Centrosome amplification results into genetic instability and predisposes cells to neoplastic transformation. Supernumerary centrosomes trigger p53 stabilization dependent on the PIDDosome (a multiprotein complex composed by PIDD1, RAIDD and Caspase-2), whose activation results in cleavage of p53's key inhibitor, MDM2. Here, we demonstrate that PIDD1 is recruited to mature centrosomes by the centriolar distal appendage protein ANKRD26. PIDDosome-dependent Caspase-2 activation requires not only PIDD1 centrosomal localization, but also its autoproteolysis. Following cytokinesis failure, supernumerary centrosomes form clusters, which appear to be necessary for PIDDosome activation. In addition, in the context of DNA damage, activation of the complex results from a p53-dependent elevation of PIDD1 levels independently of centrosome amplification. We propose that PIDDosome activation can in both cases be promoted by an ANKRD26-dependent local increase in PIDD1 concentration close to the centrosome. Collectively, these findings provide a paradigm for how centrosomes can contribute to cell fate determination by igniting a signalling cascade.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Proteomics (Schmidt)
UniBasel Contributors:Schmidt, Alexander
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Embo press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Jan 2022 12:35
Deposited On:22 Jan 2022 12:35

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