The PIDDosome activates p53 in response to supernumerary centrosomes

Fava, Luca L. and Schuler, Fabian and Sladky, Valentina and Haschka, Manuel D. and Soratroi, Claudia and Eiterer, Lisa and Demetz, Egon and Weiss, Guenter and Geley, Stephan and Nigg, Erich A. and Villunger, Andreas. (2017) The PIDDosome activates p53 in response to supernumerary centrosomes. Genes & Development, 31 (1). pp. 34-45.

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Centrosomes, the main microtubule-organizing centers in animal cells, are replicated exactly once during the cell division cycle to form the poles of the mitotic spindle. Supernumerary centrosomes can lead to aberrant cell division and have been causally linked to chromosomal instability and cancer. Here, we report that an increase in the number of mature centrosomes, generated by disrupting cytokinesis or forcing centrosome overduplication, triggers the activation of the PIDDosome multiprotein complex, leading to Caspase-2-mediated MDM2 cleavage, p53 stabilization, and p21-dependent cell cycle arrest. This pathway also restrains the extent of developmentally scheduled polyploidization by regulating p53 levels in hepatocytes during liver organogenesis. Taken together, the PIDDosome acts as a first barrier, engaging p53 to halt the proliferation of cells carrying more than one mature centrosome to maintain genome integrity.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Cell Biology (Nigg)
UniBasel Contributors:Nigg, Erich A.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Cold Spring Harbor Laboratory Press
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:19 Oct 2017 08:55
Deposited On:19 Oct 2017 08:55

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