Mad2 Is a Critical Mediator of the Chromosome Instability Observed upon Rb and p53 Pathway Inhibition

Schvartzman, Juan-Manuel, Duijf, Pascal H. G., Sotillo, Rocio, Coker, Courtney and Benezra, Robert (2011) Mad2 Is a Critical Mediator of the Chromosome Instability Observed upon Rb and p53 Pathway Inhibition. Cancer Cell, 19 6: 701-714. doi:10.1016/j.ccr.2011.04.017


Author Schvartzman, Juan-Manuel
Duijf, Pascal H. G.
Sotillo, Rocio
Coker, Courtney
Benezra, Robert
Title Mad2 Is a Critical Mediator of the Chromosome Instability Observed upon Rb and p53 Pathway Inhibition
Journal name Cancer Cell   Check publisher's open access policy
ISSN 1535-6108
1878-3686
Publication date 2011-06
Year available 2011
Sub-type Article (original research)
DOI 10.1016/j.ccr.2011.04.017
Volume 19
Issue 6
Start page 701
End page 714
Total pages 14
Place of publication Cambridge, MA United States
Publisher Cell Press
Collection year 2012
Language eng
Formatted abstract
Multiple mechanisms have been proposed to explain how Rb and p53 tumor suppressor loss lead to chromosome instability (CIN). It was recently shown that Rb pathway inhibition causes overexpression of the mitotic checkpoint gene Mad2, but whether Mad2 overexpression is required to generate CIN in this context is unknown. Here, we show that CIN in cultured cells lacking Rb family proteins requires Mad2 upregulation and that this upregulation is also necessary for CIN and tumor progression in vivo. Mad2 is also repressed by p53 and its upregulation is required for CIN in a p53 mutant tumor model. These results demonstrate that Mad2 overexpression is a critical mediator of the CIN observed upon inactivation of two major tumor suppressor pathways.
Keyword Cel -Cycle Progression
Genomic Instability
Mammalian Cells
DNA damage
Cancer
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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Created: Thu, 12 Dec 2013, 09:10:19 EST by Pascal Duijf on behalf of UQ Diamantina Institute