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Publication : Mad2 is a critical mediator of the chromosome instability observed upon Rb and p53 pathway inhibition.

First Author  Schvartzman JM Year  2011
Journal  Cancer Cell Volume  19
Issue  6 Pages  701-14
PubMed ID  21665145 Mgi Jnum  J:173563
Mgi Id  MGI:5014455 Doi  10.1016/j.ccr.2011.04.017
Citation  Schvartzman JM, et al. (2011) Mad2 Is a Critical Mediator of the Chromosome Instability Observed upon Rb and p53 Pathway Inhibition. Cancer Cell 19(6):701-14
abstractText  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.
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