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Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells
Published on: July 30, 2020
Aurora B hyperactivation by Bub1 overexpression promotes chromosome missegregation
Robin M Ricke1, Jan M van Deursen
1Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA.
Cell Cycle (Georgetown, Tex.)
|October 29, 2011
Summary
Overexpression of the mitotic kinase Bub1 drives cancer by causing aneuploidization, leading to tumor development. This process involves increased Aurora B activity and chromosome missegregation, highlighting Bub1
Area of Science:
- Cell Biology
- Cancer Biology
- Genetics
Background:
- High expression of the mitotic kinase Bub1 is linked to various human cancers and poor clinical prognosis.
- The specific role of Bub1 in driving tumorigenesis independently was previously unknown.
Purpose of the Study:
- To investigate the oncogenic properties of Bub1 and its role in driving tumorigenesis.
- To elucidate the mechanisms by which Bub1 overexpression leads to cancer development.
Main Methods:
- Generation of transgenic mice overexpressing Bub1 in multiple tissues.
- Analysis of aneuploidization, chromosome alignment, and mitotic checkpoint function in Bub1 transgenic mice.
- Assessment of spontaneous tumor development and Myc-induced lymphomagenesis.
Main Results:
- Bub1 overexpression in transgenic mice resulted in widespread aneuploidization.
- These mice developed spontaneous tumors and showed accelerated Myc-induced lymphomagenesis.
- Chromosome misalignment and lagging chromosomes were observed, linked to increased Aurora B activity.
Conclusions:
- Bub1 possesses oncogenic properties and can drive tumorigenesis.
- Aneuploidization and tumor formation are consequences of Aurora B-dependent chromosome missegregation mediated by Bub1.
- Bub1-dependent Aurora B activation plays a crucial role in cancer development by affecting error correction during mitosis.
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