TAp73α binds the kinetochore proteins Bub1 and Bub3 resulting in polyploidy

Patrizia Vernole, Michael H. Neale, Daniela Barcaroli, Eliana Munarriz, Richard A. Knight, Richard Tomasini, Tak W. Mak, Gerry Melino, Vincenzo De Laurenzi

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Aneuploidy is a characteristic of most solid tumors, often associated with negative prognosis. It can arise from two principal mechanisms: from a tetraploid intermediate state, or directly from errors at cell division. The control of cell division, crucial to maintain genomic stability, is still poorly understood in its relationship to aneuploidy. Here we show that the TAp73α isoform induces polyploidy when overexpressed. This is possibly due to the interaction of TAp73α with kinetochore-related proteins leading to the alteration of mitotic checkpoint abilities. TAp73α but not p53 or any of the other p73 isoforms binds Bub1 and Bub3. Since TAp73α is frequently overexpressed in cancer, this interaction may contribute to the aneuploidy observed in cancer progression. Our results suggest a novel molecular mechanism leading to aneuploidy involving interference of TAp73α with Bub1 and Bub3 resulting in an altered mitotic checkpoint.

Original languageEnglish
Pages (from-to)421-429
Number of pages9
JournalCell Cycle
Volume8
Issue number3
Publication statusPublished - Feb 1 2009

Fingerprint

Kinetochores
Polyploidy
Aneuploidy
M Phase Cell Cycle Checkpoints
Cell Division
Protein Isoforms
Proteins
Neoplasms
Tetraploidy
Genomic Instability

Keywords

  • Aneuploidy
  • Bub1
  • Bub3
  • c-anaphases
  • p53
  • p73
  • Polyploidy

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology
  • Medicine(all)

Cite this

Vernole, P., Neale, M. H., Barcaroli, D., Munarriz, E., Knight, R. A., Tomasini, R., ... De Laurenzi, V. (2009). TAp73α binds the kinetochore proteins Bub1 and Bub3 resulting in polyploidy. Cell Cycle, 8(3), 421-429.

TAp73α binds the kinetochore proteins Bub1 and Bub3 resulting in polyploidy. / Vernole, Patrizia; Neale, Michael H.; Barcaroli, Daniela; Munarriz, Eliana; Knight, Richard A.; Tomasini, Richard; Mak, Tak W.; Melino, Gerry; De Laurenzi, Vincenzo.

In: Cell Cycle, Vol. 8, No. 3, 01.02.2009, p. 421-429.

Research output: Contribution to journalArticle

Vernole, P, Neale, MH, Barcaroli, D, Munarriz, E, Knight, RA, Tomasini, R, Mak, TW, Melino, G & De Laurenzi, V 2009, 'TAp73α binds the kinetochore proteins Bub1 and Bub3 resulting in polyploidy', Cell Cycle, vol. 8, no. 3, pp. 421-429.
Vernole P, Neale MH, Barcaroli D, Munarriz E, Knight RA, Tomasini R et al. TAp73α binds the kinetochore proteins Bub1 and Bub3 resulting in polyploidy. Cell Cycle. 2009 Feb 1;8(3):421-429.
Vernole, Patrizia ; Neale, Michael H. ; Barcaroli, Daniela ; Munarriz, Eliana ; Knight, Richard A. ; Tomasini, Richard ; Mak, Tak W. ; Melino, Gerry ; De Laurenzi, Vincenzo. / TAp73α binds the kinetochore proteins Bub1 and Bub3 resulting in polyploidy. In: Cell Cycle. 2009 ; Vol. 8, No. 3. pp. 421-429.
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