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.
read more
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.
read more
Chat with Paper
AI Agents for this Paper
Find similar papers on Google Scholar, PubMed and Arxiv
Write a critical review of this paper
Analyze citations of this paper to find unaddressed research gaps
Citations
Human centrosome organization and function in interphase and mitosis.
TL;DR: In this article, the authors summarize the current knowledge about the centriole and centrosome architecture and discuss the structured organization of centrosomes in interphase, focusing on localization/function relationship.
63
The evolution of regulated cell death pathways in animals and their evasion by pathogens
Bart Tummers,Douglas R. Green +1 more
TL;DR: The molecular pathways of regulated cell death, their roles in infection, and how they are perturbed by viruses and bacteria are reviewed, providing insights into the coevolution of host-pathogen interactions and cell death pathways.
63
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.
59
The p53-caspase-2 axis in the cell cycle and DNA damage response.
TL;DR: Caspase-2 plays an important role in the regulation of p53 in response to cellular stress and DNA damage to prevent the proliferation and accumulation of damaged or aberrant cells as discussed by the authors.
When cell death goes wrong: inflammatory outcomes of failed apoptosis and mitotic cell death
Florian J. Bock,Joel S. Riley +1 more
TL;DR: In this article , the authors discuss how the death receptor and mitochondrial pathways of apoptosis can activate inflammation and highlight how cell death due to mitotic stress might be a special case when it comes to cell death and the induction of inflammation.
References
E2F-Family Members Engage the PIDDosome to Limit Hepatocyte Ploidy in Liver Development and Regeneration.
Valentina C. Sladky,Katja Knapp,Claudia Soratroi,Julia Heppke,Felix Eichin,Lourdes Rocamora-Reverte,Tamas G. Szabo,Laura Bongiovanni,Bart Westendorp,Eva Moreno,Elsbeth A. van Liere,Bjorn Bakker,Diana C.J. Spierings,René Wardenaar,David Pereyra,Patrick Starlinger,Simon Schultze,Michael Trauner,Tatjana Stojakovic,Hubert Scharnagl,Luca L. Fava,Floris Foijer,Alain de Bruin,Alain de Bruin,Andreas Villunger,Andreas Villunger +25 more
TL;DR: It is shown that the PIDDosome, a signaling platform essential for caspase-2-activation, limits hepatocyte ploidy and is instructed by the E2F network to control p53 in the developing as well as regenerating liver.
58
BubR1 Promotes Bub3-Dependent APC/C Inhibition during Spindle Assembly Checkpoint Signaling
Katharina Overlack,Tanja Bange,Florian Weissmann,Alex C. Faesen,Stefano Maffini,Ivana Primorac,Franziska Müller,Jan-Michael Peters,Andrea Musacchio,Andrea Musacchio +9 more
TL;DR: Small sequence differences in Bub1 and BubR1 direct Bub3 to different phosphorylated targets in the SAC signaling cascade, suggesting that BubR 1:Bub3 recognition and inhibition of APC/C requires phosphorylation.
45
Human cytomegalovirus glycoprotein B variants affect viral entry, cell fusion, and genome stability
TL;DR: It is shown that HCMV activates caspase-2, an apoptosis-related enzyme activated by DNA damage and abnormal mitosis, in a strain-specific manner, and that specific glycoprotein B variants with increased fusogenicity might affect H CMV transmission and pathogenicity.
32
Potent and selective caspase-2 inhibitor prevents MDM-2 cleavage in reversine-treated colon cancer cells.
Marcin Poreba,Wioletta Rut,Katarzyna Groborz,Katarzyna Groborz,Scott J. Snipas,Guy S. Salvesen,Marcin Drag,Marcin Drag +7 more
TL;DR: The champion inhibitor (NH-23-C2) is used in reversine-treated HCT-116 colon cancer cells to selectively block caspase-2 activity and caspases-2-mediated MDM-2 cleavage, and it is shown that NH-23 -C2 does not block cospase-3 or caspas-8, which makes it a powerful chemical tool to dissect the true role of casp enzyme-2 in various biological setups.
Pericentriolar material analyses in normal esophageal mucosa, Barrett's metaplasia and adenocarcinoma.
Daniela Segat,Mauro Cassaro,Emanuela Dazzo,Lucia Cavallini,Chiara Romualdi,Renato Salvador,Maria Pia Vitale,Libero Vitiello,Matteo Fassan,Massimo Rugge,Giovanni Zaninotto,Ermanno Ancona,Maurizio David Baroni +12 more
TL;DR: Findings strongly support the hypothesis that the three esophageal histotypes (one being pathological, one being pathological) can have a common progenitor, and suggest PCM as a possible prognostic marker for tumor relapse.
19