Figure 7.

Proposed model of PIDDosome-mediated cell cycle arrest in response to supernumerary centrosomes. Cycling somatic cells carry one centrosome in G1, composed of one mother centriole (1)—decorated by appendages (triangles) and positive for PIDD1 (red)—and one daughter centriole (2). Both centrioles are connected by a flexible linker. During S phase, each centriole nucleates one procentriole (3 and 4). Upon mitotic traverse, the daughter centriole matures to mother and acquires appendages and PIDD1 positivity (2). In the absence of cytokinesis, the two mother centrioles (1 and 2) that would normally be inherited by the two daughter cells undergo clustering and promote PIDDosome assembly. This promotes Caspase-2 activation, which results in MDM2 cleavage at D367. The N-terminal fragment of MDM2 binds p53, leading to its stabilization and p21 transcription-dependent cell cycle arrest.