p53 dependent centrosome clustering prevents multipolar mitosis in tetraploid cells.
BACKGROUND: p53 abnormality and aneuploidy often coexist in human tumors, and tetraploidy is considered as an intermediate between normal diploidy and aneuploidy. The purpose of this study was to investigate whether and how p53 influences the transformation from tetraploidy to aneuploidy. PRINCIPAL...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3208627?pdf=render |
| _version_ | 1811264663929749504 |
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| author | Qiyi Yi Xiaoyu Zhao Yun Huang Tieliang Ma Yingyin Zhang Heli Hou Howard J Cooke Da-Qing Yang Mian Wu Qinghua Shi |
| author_facet | Qiyi Yi Xiaoyu Zhao Yun Huang Tieliang Ma Yingyin Zhang Heli Hou Howard J Cooke Da-Qing Yang Mian Wu Qinghua Shi |
| author_sort | Qiyi Yi |
| collection | DOAJ |
| description | BACKGROUND: p53 abnormality and aneuploidy often coexist in human tumors, and tetraploidy is considered as an intermediate between normal diploidy and aneuploidy. The purpose of this study was to investigate whether and how p53 influences the transformation from tetraploidy to aneuploidy. PRINCIPAL FINDINGS: Live cell imaging was performed to determine the fates and mitotic behaviors of several human and mouse tetraploid cells with different p53 status, and centrosome and spindle immunostaining was used to investigate centrosome behaviors. We found that p53 dominant-negative mutation, point mutation, or knockout led to a 2∼ 33-fold increase of multipolar mitosis in N/TERT1, 3T3 and mouse embryonic fibroblasts (MEFs), while mitotic entry and cell death were not significantly affected. In p53-/- tetraploid MEFs, the ability of centrosome clustering was compromised, while centrosome inactivation was not affected. Suppression of RhoA/ROCK activity by specific inhibitors in p53-/- tetraploid MEFs enhanced centrosome clustering, decreased multipolar mitosis from 38% to 20% and 16% for RhoA and ROCK, respectively, while expression of constitutively active RhoA in p53+/+ tetraploid 3T3 cells increased the frequency of multipolar mitosis from 15% to 35%. CONCLUSIONS: p53 could not prevent tetraploid cells entering mitosis or induce tetraploid cell death. However, p53 abnormality impaired centrosome clustering and lead to multipolar mitosis in tetraploid cells by modulating the RhoA/ROCK signaling pathway. |
| first_indexed | 2024-04-12T20:08:26Z |
| format | Article |
| id | doaj.art-c2aa906043bb4bd69e8b5bda0884adf1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T20:08:26Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c2aa906043bb4bd69e8b5bda0884adf12022-12-22T03:18:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01611e2730410.1371/journal.pone.0027304p53 dependent centrosome clustering prevents multipolar mitosis in tetraploid cells.Qiyi YiXiaoyu ZhaoYun HuangTieliang MaYingyin ZhangHeli HouHoward J CookeDa-Qing YangMian WuQinghua ShiBACKGROUND: p53 abnormality and aneuploidy often coexist in human tumors, and tetraploidy is considered as an intermediate between normal diploidy and aneuploidy. The purpose of this study was to investigate whether and how p53 influences the transformation from tetraploidy to aneuploidy. PRINCIPAL FINDINGS: Live cell imaging was performed to determine the fates and mitotic behaviors of several human and mouse tetraploid cells with different p53 status, and centrosome and spindle immunostaining was used to investigate centrosome behaviors. We found that p53 dominant-negative mutation, point mutation, or knockout led to a 2∼ 33-fold increase of multipolar mitosis in N/TERT1, 3T3 and mouse embryonic fibroblasts (MEFs), while mitotic entry and cell death were not significantly affected. In p53-/- tetraploid MEFs, the ability of centrosome clustering was compromised, while centrosome inactivation was not affected. Suppression of RhoA/ROCK activity by specific inhibitors in p53-/- tetraploid MEFs enhanced centrosome clustering, decreased multipolar mitosis from 38% to 20% and 16% for RhoA and ROCK, respectively, while expression of constitutively active RhoA in p53+/+ tetraploid 3T3 cells increased the frequency of multipolar mitosis from 15% to 35%. CONCLUSIONS: p53 could not prevent tetraploid cells entering mitosis or induce tetraploid cell death. However, p53 abnormality impaired centrosome clustering and lead to multipolar mitosis in tetraploid cells by modulating the RhoA/ROCK signaling pathway.http://europepmc.org/articles/PMC3208627?pdf=render |
| spellingShingle | Qiyi Yi Xiaoyu Zhao Yun Huang Tieliang Ma Yingyin Zhang Heli Hou Howard J Cooke Da-Qing Yang Mian Wu Qinghua Shi p53 dependent centrosome clustering prevents multipolar mitosis in tetraploid cells. PLoS ONE |
| title | p53 dependent centrosome clustering prevents multipolar mitosis in tetraploid cells. |
| title_full | p53 dependent centrosome clustering prevents multipolar mitosis in tetraploid cells. |
| title_fullStr | p53 dependent centrosome clustering prevents multipolar mitosis in tetraploid cells. |
| title_full_unstemmed | p53 dependent centrosome clustering prevents multipolar mitosis in tetraploid cells. |
| title_short | p53 dependent centrosome clustering prevents multipolar mitosis in tetraploid cells. |
| title_sort | p53 dependent centrosome clustering prevents multipolar mitosis in tetraploid cells |
| url | http://europepmc.org/articles/PMC3208627?pdf=render |
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