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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Main Authors: Nakade Koji, Wasylyk Bohdan, Yokoyama Kazunari K.
Format: Article
Language:English
Published: De Gruyter 2010-05-01
Series:Biomolecular Concepts
Subjects:
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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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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