Nakade Koji, Wasylyk Bohdan, Yokoyama Kazunari K
Biomol Concepts. 2010 May 1;1(1):49-58. doi: 10.1515/bmc.2010.008.
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.
作为对不断累积的细胞应激的反应，细胞通过进入衰老阶段来保护自身免受异常生长的影响。衰老主要由p16Ink4a/Arf基因座的基因产物控制。在小鼠细胞中，p16Ink4a和Arf的表达在细胞培养增殖过程中持续增加。该基因座的转录受到复杂的调控。p16Ink4a和Arf对正负信号独立作出反应，并且整个基因座通过依赖于多梳抑制复合物1和2（PRC1和PRC2）的组蛋白甲基化在表观遗传上受到抑制。事实上，PRC在年轻的增殖细胞中与p16Ink4a/Arf基因座结合，而在衰老细胞中解离。因此，似乎调节PRC结合和解离的染色质重塑因子可能是衰老程序中的重要参与者。在这里，我们总结了介导细胞衰老的分子机制，并介绍了Jun二聚化蛋白2（JDP2），它作为一种通过介导PRC从p16Ink4a/Arf基因座解离来调节复制性衰老的因子。
