Centriolar distal appendages activate the centrosome-PIDDosome-p53 signalling axis via ANKRD26
Matteo Burigotto,Alessia Mattivi,Daniele Migliorati,Giovanni Magnani,Chiara Valentini,Michela Roccuzzo,Martin Offterdinger,Massimo Pizzato,Alexander Schmidt,Andreas Villunger,Andreas Villunger,Stefano Maffini,Luca L. Fava +12 more
TL;DR: In this paper, the authors demonstrate that PIDD1 is recruited to mature centrosomes by the centriolar distal appendage protein ANKRD26, which can be used to promote PIDDosome-dependent Caspase-2 activation.
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Abstract: 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.
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Centriolar distal appendages activate the centrosome-PIDDosome-p53 signalling axis via ANKRD26
Matteo Burigotto,Alessia Mattivi,Daniele Migliorati,Giovanni Magnani,Chiara Valentini,Michela Roccuzzo,Martin Offterdinger,Massimo Pizzato,Alexander Schmidt,Andreas Villunger,Andreas Villunger,Stefano Maffini,Luca L. Fava +12 more
TL;DR: In this paper, the authors demonstrate that PIDD1 is recruited to mature centrosomes by the centriolar distal appendage protein ANKRD26, which can be used to promote PIDDosome-dependent Caspase-2 activation.
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References
Flexible stoichiometry and asymmetry of the PIDDosome core complex by heteronuclear NMR spectroscopy and mass spectrometry.
Lily A. Nematollahi,Acely Garza-Garcia,Cherine Bechara,Diego Esposito,Nina Morgner,Carol V. Robinson,Paul C. Driscoll +6 more
TL;DR: The NMR data for this system are consistent with the formation of a structure homologous to the PIDDosome core and suggest that the crystal structure is representative of only the heaviest species in solution and that two RAIDD-DDs are loosely attached to the 5:5 core.
The Centrosome, a Multitalented Renaissance Organelle
TL;DR: New roles for the centrosome are reviewed in directing membrane traffic, the immunological synapse, and the stress response, including those related to the immune response and cell cycle arrest.
The autoregulated instability of Polo-like kinase 4 limits centrosome duplication to once per cell cycle
Andrew J. Holland,Daniele Fachinetti,Quan Zhu,Manuel Bauer,Inder M. Verma,Erich A. Nigg,Don W. Cleveland +6 more
TL;DR: It is demonstrated that this autoregulated instability controls the abundance of endogenous Plk4, which guards against genome instability by limiting centrosome duplication to once per cell cycle.
p53 mitotic centrosome localization preserves centrosome integrity and works as sensor for the mitotic surveillance pathway
Claudia Contadini,Laura Monteonofrio,Ilaria Virdia,Andrea Prodosmo,Davide Valente,Luciana Chessa,Antonio Musio,Luca L. Fava,Cinzia Rinaldo,Giuliana Di Rocco,Silvia Soddu +10 more
TL;DR: Findings indicate that, in nontransformed human cells, centrosomal p53 contributes to safeguard genome integrity by working as sensor for the mitotic surveillance pathway.
The Cilium: Cellular Antenna and Central Processing Unit
Jarema Malicki,Colin A. Johnson +1 more
TL;DR: An integrated view of these regulatory inputs will be necessary to understand ciliogenesis and its wider relevance to human biology.