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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: MPI-CBG Publications 2012-arch     Display Documents



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ID: 645204.0, MPI für molekulare Zellbiologie und Genetik / MPI-CBG Publications 2012-arch
Tpx2 controls spindle integrity, genome stability, and tumor development.
Authors:Aguirre-Portolés, Cristina; Bird, Alexander W.; Hyman, Anthony A.; Cañamero, Marta; Castro, Ignacio Pérez de; Malumbres, Marcos
Date of Publication (YYYY-MM-DD):2012
Title of Journal:Cancer Research
Volume:72
Issue / Number:6
Start Page:1518
End Page:1528
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Tpx2 is a microtubule-associated protein that activates the cell-cycle kinase Aurora A and regulates the mitotic spindle. Overexpression of Tpx2 is associated with the development of different human tumors and strongly correlates with chromosomal instability. By analyzing a conditional null mutation in the mouse Tpx2 gene, we show here that Tpx2 expression is essential for spindle function and chromosome segregation in the mouse embryo. Conditional genetic ablation of Tpx2 in primary cultures resulted in deficient microtubule nucleation from DNA and aberrant spindles during prometaphase. These cells eventually exited from mitosis without chromosome segregation. In addition, Tpx2 haploinsufficiency led to the accumulation of aneuploidies in vivo and increased susceptibility to spontaneous lymphomas and lung tumors. Together, our findings indicate that Tpx2 is essential for maintaining genomic stability through its role in spindle regulation. Subtle changes in Tpx2 expression may favor tumor development in vivo.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:nn
Affiliations:MPI für molekulare Zellbiologie und Genetik
Identifiers:LOCALID:4895
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