Sophisticated framework between cell cycle arrest and apoptosis induction based on p53 dynamics.
The tumor suppressor, p53, regulates several gene expressions that are related to the DNA repair protein, cell cycle arrest and apoptosis induction, which activates the implementation of both cell cycle arrest and induction of apoptosis. However, it is not clear how p53 specifically regulates the im...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2650779?pdf=render |
| _version_ | 1828174348330991616 |
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| author | Hiroyuki Hamada Yoshihiko Tashima Yu Kisaka Kazunari Iwamoto Taizo Hanai Yukihiro Eguchi Masahiro Okamoto |
| author_facet | Hiroyuki Hamada Yoshihiko Tashima Yu Kisaka Kazunari Iwamoto Taizo Hanai Yukihiro Eguchi Masahiro Okamoto |
| author_sort | Hiroyuki Hamada |
| collection | DOAJ |
| description | The tumor suppressor, p53, regulates several gene expressions that are related to the DNA repair protein, cell cycle arrest and apoptosis induction, which activates the implementation of both cell cycle arrest and induction of apoptosis. However, it is not clear how p53 specifically regulates the implementation of these functions. By applying several well-known kinetic mathematical models, we constructed a novel model that described the influence that DNA damage has on the implementation of both the G2/M phase cell cycle arrest and the intrinsic apoptosis induction via its activation of the p53 synthesis process. The model, which consisted of 32 dependent variables and 115 kinetic parameters, was used to examine interference by DNA damage in the implementation of both G2/M phase cell cycle arrest and intrinsic apoptosis induction. A low DNA damage promoted slightly the synthesis of p53, which showed a sigmoidal behavior with time. In contrast, in the case of a high DNA damage, the p53 showed an oscillation behavior with time. Regardless of the DNA damage level, there were delays in the G2/M progression. The intrinsic apoptosis was only induced in situations where grave DNA damage produced an oscillation of p53. In addition, to wreck the equilibrium between Bcl-2 and Bax the induction of apoptosis required an extreme activation of p53 produced by the oscillation dynamics, and was only implemented after the release of the G2/M phase arrest. When the p53 oscillation is observed, there is possibility that the cell implements the apoptosis induction. Moreover, in contrast to the cell cycle arrest system, the apoptosis induction system is responsible for safeguarding the system that suppresses malignant transformations. The results of these experiments will be useful in the future for elucidating of the dominant factors that determine the cell fate such as normal cell cycles, cell cycle arrest and apoptosis. |
| first_indexed | 2024-04-12T04:10:01Z |
| format | Article |
| id | doaj.art-bd086858986b4a93869100f31e76b01f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T04:10:01Z |
| publishDate | 2009-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-bd086858986b4a93869100f31e76b01f2022-12-22T03:48:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0143e479510.1371/journal.pone.0004795Sophisticated framework between cell cycle arrest and apoptosis induction based on p53 dynamics.Hiroyuki HamadaYoshihiko TashimaYu KisakaKazunari IwamotoTaizo HanaiYukihiro EguchiMasahiro OkamotoThe tumor suppressor, p53, regulates several gene expressions that are related to the DNA repair protein, cell cycle arrest and apoptosis induction, which activates the implementation of both cell cycle arrest and induction of apoptosis. However, it is not clear how p53 specifically regulates the implementation of these functions. By applying several well-known kinetic mathematical models, we constructed a novel model that described the influence that DNA damage has on the implementation of both the G2/M phase cell cycle arrest and the intrinsic apoptosis induction via its activation of the p53 synthesis process. The model, which consisted of 32 dependent variables and 115 kinetic parameters, was used to examine interference by DNA damage in the implementation of both G2/M phase cell cycle arrest and intrinsic apoptosis induction. A low DNA damage promoted slightly the synthesis of p53, which showed a sigmoidal behavior with time. In contrast, in the case of a high DNA damage, the p53 showed an oscillation behavior with time. Regardless of the DNA damage level, there were delays in the G2/M progression. The intrinsic apoptosis was only induced in situations where grave DNA damage produced an oscillation of p53. In addition, to wreck the equilibrium between Bcl-2 and Bax the induction of apoptosis required an extreme activation of p53 produced by the oscillation dynamics, and was only implemented after the release of the G2/M phase arrest. When the p53 oscillation is observed, there is possibility that the cell implements the apoptosis induction. Moreover, in contrast to the cell cycle arrest system, the apoptosis induction system is responsible for safeguarding the system that suppresses malignant transformations. The results of these experiments will be useful in the future for elucidating of the dominant factors that determine the cell fate such as normal cell cycles, cell cycle arrest and apoptosis.http://europepmc.org/articles/PMC2650779?pdf=render |
| spellingShingle | Hiroyuki Hamada Yoshihiko Tashima Yu Kisaka Kazunari Iwamoto Taizo Hanai Yukihiro Eguchi Masahiro Okamoto Sophisticated framework between cell cycle arrest and apoptosis induction based on p53 dynamics. PLoS ONE |
| title | Sophisticated framework between cell cycle arrest and apoptosis induction based on p53 dynamics. |
| title_full | Sophisticated framework between cell cycle arrest and apoptosis induction based on p53 dynamics. |
| title_fullStr | Sophisticated framework between cell cycle arrest and apoptosis induction based on p53 dynamics. |
| title_full_unstemmed | Sophisticated framework between cell cycle arrest and apoptosis induction based on p53 dynamics. |
| title_short | Sophisticated framework between cell cycle arrest and apoptosis induction based on p53 dynamics. |
| title_sort | sophisticated framework between cell cycle arrest and apoptosis induction based on p53 dynamics |
| url | http://europepmc.org/articles/PMC2650779?pdf=render |
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