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THE REGULATION OF BubR1 EXPRESSION BY p53: A ROLE FOR p53 IN THE MITOTIC SPINDLE CHECKPOINT AND CHROMOSOME INSTABILITY

STUABACH, AMY ELIZABETH
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1100831777

Abstract Details

2004, MS, University of Cincinnati, Medicine : Cell and Molecular Biology.
During mitosis, chromosomes must segregate equally to daughter cells thus ensuring genomic stability. The tumor suppressor protein, p53, plays a key role in maintaining a stable genome; cells lacking p53 display an increased frequency of chromosome segregation errors and an abnormal amplification of centrosomes. It had been reported that while early passage p53-/- mouse cells in culture are karyotypically heterogeneous, on prolonged culture they undergo karyotypic convergence. These late passage cells are aneuploid yet karyotypically homogeneous and contain numerically normal centrosomes. Microarray analysis has identified the spindle checkpoint protein, BuBR1 as a protein that is expressed at a higher level in late passage p53 -/- mouse cells. We have shown that BubR1 expression is significantly higher in p53 +/+ mouse fibroblasts as compared to p53 -/- mouse fibroblasts. In order to determine the p53 responsive element within the BubR1 promoter we have amplified a 2 kb portion of the mouse BubR1 promoter and cloned this portion as well as 2 other smaller portions of the promoter into a luciferase expression vector. We have shown that the transcriptonal activity of the BubR1 promoter is upregulated at a higher level in p53 +/+ cells as compared to p53 -/- cells and this upregulation is enhanced by the addition of the microtubule inhibitor, nocodazole. The transcriptional activity of this promoter is also increasingly upregulated in the presence of increasing levels of p53. The functional significance of the regulation of BubR1 expression by p53 was ascertained by determining that BubR1 is the critical component missing in p53 -/- cells causing them to be unable to halt the re-replication of the genome and to stop the development of polyploidy when these cells were cultured in the presence of nocodazole.
Dr. Kenji Fukasawa (Advisor)
75 p.
BubR1; p53; mitotic spindle checkpoint; chromosome instability; aneuploidy; cancer

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Citations

  • STUABACH, A. E. (2004). THE REGULATION OF BubR1 EXPRESSION BY p53: A ROLE FOR p53 IN THE MITOTIC SPINDLE CHECKPOINT AND CHROMOSOME INSTABILITY [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1100831777

    APA Style (7th edition)

  • STUABACH, AMY. THE REGULATION OF BubR1 EXPRESSION BY p53: A ROLE FOR p53 IN THE MITOTIC SPINDLE CHECKPOINT AND CHROMOSOME INSTABILITY. 2004. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1100831777.

    MLA Style (8th edition)

  • STUABACH, AMY. "THE REGULATION OF BubR1 EXPRESSION BY p53: A ROLE FOR p53 IN THE MITOTIC SPINDLE CHECKPOINT AND CHROMOSOME INSTABILITY." Master's thesis, University of Cincinnati, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1100831777

    Chicago Manual of Style (17th edition)

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© 2004, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.