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The circadian mutation PER2(S662G) is linked to cell cycle progression and tumorigenesis

Circadian oscillation and cell cycle progression are the two most essential rhythmic events present in almost all organisms. Circadian rhythms keep track of time and provide temporal regulation with a period of about 24 h. The cell cycle is optimized for growth and division, but not for time keeping...

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Autores principales: Gu, X, Xing, L, Shi, G, Liu, Z, Wang, X, Qu, Z, Wu, X, Dong, Z, Gao, X, Liu, G, Yang, L, Xu, Y
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278723/
https://www.ncbi.nlm.nih.gov/pubmed/21818120
http://dx.doi.org/10.1038/cdd.2011.103
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author Gu, X
Xing, L
Shi, G
Liu, Z
Wang, X
Qu, Z
Wu, X
Dong, Z
Gao, X
Liu, G
Yang, L
Xu, Y
author_facet Gu, X
Xing, L
Shi, G
Liu, Z
Wang, X
Qu, Z
Wu, X
Dong, Z
Gao, X
Liu, G
Yang, L
Xu, Y
author_sort Gu, X
collection PubMed
description Circadian oscillation and cell cycle progression are the two most essential rhythmic events present in almost all organisms. Circadian rhythms keep track of time and provide temporal regulation with a period of about 24 h. The cell cycle is optimized for growth and division, but not for time keeping. Circadian gated cell divisions are observed in nearly all organisms. However, the implications of this coupling to the physiology of mammals are unknown. A mutation (S662G) in the clock protein PERIOD2 (PER2) is responsible for familial advanced sleep phase syndrome in which sleep onset occurs in the early evening and wakefulness occurs in the early morning. Here, we provide evidence that the PER2(S662) mutation leads to enhanced resistance to X-ray-induced apoptosis and increased E1A- and RAS-mediated oncogenic transformation. Accordingly, the PER2(S662) mutation affects tumorigenesis in cancer-sensitized p53(R172H/+) mice. Finally, analyzing the clock-controlled cell cycle genes p21, c-Myc, Cyclin D1 and p27, we found that the relative phases between p21 and Cyclin D expression profiles have been changed significantly in these Per2 allele mutant mouse embryonic fibroblasts. This key role of the Per2-mediated phase alteration of p21 provides what we believe to be a novel mechanism in understanding cell cycle progression, its plasticity and its resistance to interference.
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spelling pubmed-32787232012-03-01 The circadian mutation PER2(S662G) is linked to cell cycle progression and tumorigenesis Gu, X Xing, L Shi, G Liu, Z Wang, X Qu, Z Wu, X Dong, Z Gao, X Liu, G Yang, L Xu, Y Cell Death Differ Original Paper Circadian oscillation and cell cycle progression are the two most essential rhythmic events present in almost all organisms. Circadian rhythms keep track of time and provide temporal regulation with a period of about 24 h. The cell cycle is optimized for growth and division, but not for time keeping. Circadian gated cell divisions are observed in nearly all organisms. However, the implications of this coupling to the physiology of mammals are unknown. A mutation (S662G) in the clock protein PERIOD2 (PER2) is responsible for familial advanced sleep phase syndrome in which sleep onset occurs in the early evening and wakefulness occurs in the early morning. Here, we provide evidence that the PER2(S662) mutation leads to enhanced resistance to X-ray-induced apoptosis and increased E1A- and RAS-mediated oncogenic transformation. Accordingly, the PER2(S662) mutation affects tumorigenesis in cancer-sensitized p53(R172H/+) mice. Finally, analyzing the clock-controlled cell cycle genes p21, c-Myc, Cyclin D1 and p27, we found that the relative phases between p21 and Cyclin D expression profiles have been changed significantly in these Per2 allele mutant mouse embryonic fibroblasts. This key role of the Per2-mediated phase alteration of p21 provides what we believe to be a novel mechanism in understanding cell cycle progression, its plasticity and its resistance to interference. Nature Publishing Group 2012-03 2011-08-05 /pmc/articles/PMC3278723/ /pubmed/21818120 http://dx.doi.org/10.1038/cdd.2011.103 Text en Copyright © 2012 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Original Paper
Gu, X
Xing, L
Shi, G
Liu, Z
Wang, X
Qu, Z
Wu, X
Dong, Z
Gao, X
Liu, G
Yang, L
Xu, Y
The circadian mutation PER2(S662G) is linked to cell cycle progression and tumorigenesis
title The circadian mutation PER2(S662G) is linked to cell cycle progression and tumorigenesis
title_full The circadian mutation PER2(S662G) is linked to cell cycle progression and tumorigenesis
title_fullStr The circadian mutation PER2(S662G) is linked to cell cycle progression and tumorigenesis
title_full_unstemmed The circadian mutation PER2(S662G) is linked to cell cycle progression and tumorigenesis
title_short The circadian mutation PER2(S662G) is linked to cell cycle progression and tumorigenesis
title_sort circadian mutation per2(s662g) is linked to cell cycle progression and tumorigenesis
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278723/
https://www.ncbi.nlm.nih.gov/pubmed/21818120
http://dx.doi.org/10.1038/cdd.2011.103
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