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.

中文翻译：

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中心粒远端附属物通过 ANKRD26 激活中心体-PIDDosome-p53 信号轴

中心体扩增导致遗传不稳定并使细胞易于发生肿瘤转化。多余的中心体触发 p53 的稳定依赖于 PIDDosome（一种由 PIDD1、RAIDD 和 Caspase-2 组成的多蛋白复合物），其激活导致 p53 的关键抑制剂 MDM2 裂解。在这里，我们证明 PIDD1 被中心粒远端附属物蛋白 ANKRD26 招募到成熟中心体。PIDDosome 依赖性 Caspase-2 激活不仅需要 PIDD1 中心体定位，还需要其自身蛋白水解。胞质分裂失败后，多余的中心体形成簇，这似乎是 PIDDosome 激活所必需的。此外，在 DNA 损伤的情况下，复合物的激活是由 p53 依赖性的 PIDD1 水平升高引起的，与中心体扩增无关。我们提出，在这两种情况下，PIDD1 浓度靠近中心体的 ANKRD26 依赖性局部增加都可以促进 PIDDosome 激活。总的来说，这些发现为中心体如何通过启动信号级联反应来决定细胞命运提供了范例。