The PIDDosome activates p53 in response to supernumerary centrosomes.

Genes Dev 2017 01;31(1):34-45

Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria.

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.

Download full-text PDF

Source
http://genesdev.cshlp.org/lookup/doi/10.1101/gad.289728.116
Publisher Site
http://dx.doi.org/10.1101/gad.289728.116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5287111PMC
January 2017
32 Reads

Publication Analysis

Top Keywords

supernumerary centrosomes
8
cell division
8
leading caspase-2-mediated
4
caspase-2-mediated mdm2
4
complex leading
4
multiprotein complex
4
mdm2 cleavage
4
cleavage p53
4
cell cycle
4
cycle arrest
4
p21-dependent cell
4
stabilization p21-dependent
4
p53 stabilization
4
piddosome multiprotein
4
triggers activation
4
number mature
4
mature centrosomes
4
increase number
4
report increase
4
cancer report
4

References

(Supplied by CrossRef)

Similar Publications