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

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

Bibliographic Details
Main Author: STUABACH, AMY ELIZABETH
Language:English
Published: University of Cincinnati / OhioLINK 2004
Subjects:
BubR1
p53
mitotic spindle checkpoint
chromosome instability
aneuploidy
cancer
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=ucin1100831777
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-ucin11008317772021-08-03T06:10:00Z THE REGULATION OF BubR1 EXPRESSION BY p53: A ROLE FOR p53 IN THE MITOTIC SPINDLE CHECKPOINT AND CHROMOSOME INSTABILITY STUABACH, AMY ELIZABETH BubR1 p53 mitotic spindle checkpoint chromosome instability aneuploidy cancer 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. 2004 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1100831777 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1100831777 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic BubR1
p53
mitotic spindle checkpoint
chromosome instability
aneuploidy
cancer
spellingShingle BubR1
p53
mitotic spindle checkpoint
chromosome instability
aneuploidy
cancer
STUABACH, AMY ELIZABETH
THE REGULATION OF BubR1 EXPRESSION BY p53: A ROLE FOR p53 IN THE MITOTIC SPINDLE CHECKPOINT AND CHROMOSOME INSTABILITY
author STUABACH, AMY ELIZABETH
author_facet STUABACH, AMY ELIZABETH
author_sort STUABACH, AMY ELIZABETH
title THE REGULATION OF BubR1 EXPRESSION BY p53: A ROLE FOR p53 IN THE MITOTIC SPINDLE CHECKPOINT AND CHROMOSOME INSTABILITY
title_short THE REGULATION OF BubR1 EXPRESSION BY p53: A ROLE FOR p53 IN THE MITOTIC SPINDLE CHECKPOINT AND CHROMOSOME INSTABILITY
title_full THE REGULATION OF BubR1 EXPRESSION BY p53: A ROLE FOR p53 IN THE MITOTIC SPINDLE CHECKPOINT AND CHROMOSOME INSTABILITY
title_fullStr THE REGULATION OF BubR1 EXPRESSION BY p53: A ROLE FOR p53 IN THE MITOTIC SPINDLE CHECKPOINT AND CHROMOSOME INSTABILITY
title_full_unstemmed THE REGULATION OF BubR1 EXPRESSION BY p53: A ROLE FOR p53 IN THE MITOTIC SPINDLE CHECKPOINT AND CHROMOSOME INSTABILITY
title_sort regulation of bubr1 expression by p53: a role for p53 in the mitotic spindle checkpoint and chromosome instability
publisher University of Cincinnati / OhioLINK
publishDate 2004
url http://rave.ohiolink.edu/etdc/view?acc_num=ucin1100831777
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