Multipolar mitosis of tetraploid cells: Inhibition by p53 and dependency on Mos

Ilio Vitale, Laura Senovilla, Mohamed Jema, Mickaël Michaud, Lorenzo Galluzzi, Oliver Kepp, Lisa Nanty, Alfredo Criollo, Santiago Rello-Varona, Gwenola Manic, Didier Métivier, Sonia Vivet, Nicolas Tajeddine, Nicholas Joza, Alexander Valent, Maria Castedo, Guido Kroemer

Research output: Contribution to journalArticlepeer-review

Abstract

Tetraploidy can constitute a metastable intermediate between normal diploidy and oncogenic aneuploidy. Here, we show that the absence of p53 is not only permissive for the survival but also for multipolar asymmetric divisions of tetraploid cells, which lead to the generation of aneuploid cells with a near-to-diploid chromosome content. Multipolar mitoses (which reduce the tetraploid genome to a sub-tetraploid state) are more frequent when p53 is downregulated and the product of the Mos oncogene is upregulated. Mos inhibits the coalescence of supernumerary centrosomes that allow for normal bipolar mitoses of tetraploid cells. In the absence of p53, Mos knockdown prevents multipolar mitoses and exerts genome-stabilizing effects. These results elucidate the mechanisms through which asymmetric cell division drives chromosomal instability in tetraploid cells.

Original languageEnglish
Pages (from-to)1272-1284
Number of pages13
JournalEMBO Journal
Volume29
Issue number7
DOIs
Publication statusPublished - Apr 2010

Keywords

  • Aneuploidy
  • Apoptosis
  • Centrosome
  • Colon carcinoma
  • Mitotic catastrophe

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Fingerprint

Dive into the research topics of 'Multipolar mitosis of tetraploid cells: Inhibition by p53 and dependency on Mos'. Together they form a unique fingerprint.

Cite this