TAp73alpha binds the kinetochore proteins Bub1 and Bub3 resulting in polyploidy.
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 TAp73alpha isoform induces polyploidy when overexpressed. This is possibly due to the interaction of TAp73alpha with kinetochore-related proteins leading to the alteration of mitotic checkpoint abilities. TAp73alpha but not p53 or any of the other p73 isoforms binds Bub1 and Bub3. Since TAp73alpha 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 TAp73alpha with Bub1 and Bub3 resulting in an altered mitotic checkpoint.
Vernole
Patrizia
P
Department of Public Health and Cell Biology, University of Rome Tor Vergata, Rome, Italy.
Neale
Michael H
MH
Barcaroli
Daniela
D
Munarriz
Eliana
E
Knight
Richard A
RA
Tomasini
Richard
R
Mak
Tak W
TW
Melino
Gerry
G
De Laurenzi
Vincenzo
V
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018386:Kinetochores / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D011123:Polyploidy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
C489444:BUB3 protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases