Epigenetic regulation of p16Ink4a and Arf by JDP2 in cellular senescence
In response to accumulating cellular stress, cells protect themselves from abnormal growth by entering the senescent stage. Senescence is controlled mainly by gene products from the p16Ink4a/Arf locus. In mouse cells, the expression of p16Ink4a and Arf increases continuously during proliferation in...
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Format: | Article |
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De Gruyter
2010-05-01
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Series: | Biomolecular Concepts |
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Online Access: | https://doi.org/10.1515/bmc.2010.008 |
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author | Nakade Koji Wasylyk Bohdan Yokoyama Kazunari K. |
author_facet | Nakade Koji Wasylyk Bohdan Yokoyama Kazunari K. |
author_sort | Nakade Koji |
collection | DOAJ |
description | In response to accumulating cellular stress, cells protect themselves from abnormal growth by entering the senescent stage. Senescence is controlled mainly by gene products from the p16Ink4a/Arf locus. In mouse cells, the expression of p16Ink4a and Arf increases continuously during proliferation in cell culture. Transcription from the locus is under complex control. p16Ink4a and Arf respond independently to positive and negative signals, and the entire locus is epigenetically suppressed by histone methylation that depends on the Polycomb repressive complex-1 and -2 (PRC1 and PRC2). In fact, the PRCs associate with the p16Ink4a/Arf locus in young proliferating cells and dissociate in aged senescent cells. Thus, it seems that chromatin-remodeling factors that regulate association and dissociation of PRCs might be important players in the senescence program. Here, we summarize the molecular mechanisms that mediate cellular aging and introduce the Jun dimerization protein 2 (JDP2) as a factor that regulates replicative senescence by mediating dissociation of PRCs from the p16Ink4a/Arf locus. |
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issn | 1868-5021 1868-503X |
language | English |
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spelling | doaj.art-24b0b7de74234e6f9c95e187e1b520522022-12-21T21:49:41ZengDe GruyterBiomolecular Concepts1868-50211868-503X2010-05-0111495810.1515/bmc.2010.008Epigenetic regulation of p16Ink4a and Arf by JDP2 in cellular senescenceNakade Koji0Wasylyk Bohdan1Yokoyama Kazunari K.2Gene Engineering Division, BioResource Center, RIKEN, 3-1-1, Koyadai, Ibaraki 305-0074, JapanInstitut de Génétique et de Biologie Moléculaire et Cellulaire, 1, rue Laurent Fries, Illkirch cedex 67404, FranceCenter of Excellence for Environmental Medicine, Graduate Institute of Medicine, Kaohsiung Medical University, 807 Kaohsiung, TaiwanIn response to accumulating cellular stress, cells protect themselves from abnormal growth by entering the senescent stage. Senescence is controlled mainly by gene products from the p16Ink4a/Arf locus. In mouse cells, the expression of p16Ink4a and Arf increases continuously during proliferation in cell culture. Transcription from the locus is under complex control. p16Ink4a and Arf respond independently to positive and negative signals, and the entire locus is epigenetically suppressed by histone methylation that depends on the Polycomb repressive complex-1 and -2 (PRC1 and PRC2). In fact, the PRCs associate with the p16Ink4a/Arf locus in young proliferating cells and dissociate in aged senescent cells. Thus, it seems that chromatin-remodeling factors that regulate association and dissociation of PRCs might be important players in the senescence program. Here, we summarize the molecular mechanisms that mediate cellular aging and introduce the Jun dimerization protein 2 (JDP2) as a factor that regulates replicative senescence by mediating dissociation of PRCs from the p16Ink4a/Arf locus.https://doi.org/10.1515/bmc.2010.008arfepigeneticjun dimerization protein 2 (jdp2)p16ink4a, senescence |
spellingShingle | Nakade Koji Wasylyk Bohdan Yokoyama Kazunari K. Epigenetic regulation of p16Ink4a and Arf by JDP2 in cellular senescence Biomolecular Concepts arf epigenetic jun dimerization protein 2 (jdp2) p16ink4a, senescence |
title | Epigenetic regulation of p16Ink4a and Arf by JDP2 in cellular senescence |
title_full | Epigenetic regulation of p16Ink4a and Arf by JDP2 in cellular senescence |
title_fullStr | Epigenetic regulation of p16Ink4a and Arf by JDP2 in cellular senescence |
title_full_unstemmed | Epigenetic regulation of p16Ink4a and Arf by JDP2 in cellular senescence |
title_short | Epigenetic regulation of p16Ink4a and Arf by JDP2 in cellular senescence |
title_sort | epigenetic regulation of p16ink4a and arf by jdp2 in cellular senescence |
topic | arf epigenetic jun dimerization protein 2 (jdp2) p16ink4a, senescence |
url | https://doi.org/10.1515/bmc.2010.008 |
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