AI Article Synopsis
- * The study shows that the protein ANKRD26 helps recruit another protein, PIDD1, to mature centrosomes, which is crucial for activating the PIDDosome and the associated response.
- * The activation of this complex is influenced by factors like cytokinesis failure and DNA damage, highlighting how centrosomes can impact a cell’s fate through signaling pathways.
Article 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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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883297 | PMC |
| http://dx.doi.org/10.15252/embj.2020104844 | DOI Listing |
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