RRM2B suppresses activation of the oxidative stress pathway and is up-regulated by p53 during senescence.
RRM2B suppresses activation of the oxidative stress pathway and is up-regulated by p53 during senescence.
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DOI：
10.1038/srep00822
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发表时间：
2012
影响因子：
4.6
通讯作者：
Yen, Yun
中科院分区：
文献类型：
--
作者：
Kuo, Mei-Ling;Sy, Alexander J.;Xue, Lijun;Chi, Martin;Lee, Michelle T. -C.;Yen, Terence;Chiang, Mei-Iok;Chang, Lufen;Chu, Peiguo;Yen, Yun
RRM2B是核糖核苷酸还原酶的DNA损伤诱导小亚基，是从头合成脱氧核糖核苷三磷酸的限速酶。尽管RRM2B参与DNA修复和线粒体DNA含量的维持，但RRM2B在衰老中的调控和功能尚未被证实。在这里，我们发现在人原代成纤维细胞IMR90细胞衰老过程中，RRM2B以p53依赖的方式被高度诱导，并且与邻近正常前列腺相比，RRM2B在衰老的人前列腺癌前上皮内肿瘤病变中表达水平更高。矛盾的是，在年轻成纤维细胞中，沉默RRM2B表达会导致活性氧水平增加、线粒体膜去极化和p38MAPK-和p53依赖方式的过早衰老。一致地，Rrm2b缺陷小鼠胚胎成纤维细胞的衰老诱导加速。我们的数据表明，RRM2B在衰老开始前被应激信号诱导，并防止氧化应激诱导的过早衰老。
RRM2B is the DNA damage-inducible small subunit of ribonucleotide reductase, the rate-limiting enzyme in de novo deoxyribonucleoside triphosphate synthesis. Although RRM2B is implicated in DNA repair and the maintenance of mitochondrial DNA content, the regulation and function of RRM2B in senescence have not been previously established. Here, we show that RRM2B is highly induced in a p53-dependent manner during senescence in primary human fibroblast IMR90 cells and is expressed at higher levels in senescent precancerous human prostatic intraepithelial neoplasm lesions compared to adjacent normal prostate glands. Paradoxically, silencing RRM2B expression leads to an increase in the level of reactive oxygen species, mitochondrial membrane depolarization, and premature senescence in a p38MAPK- and p53-dependent manner in young fibroblasts. Consistently, induction of senescence is accelerated in Rrm2b deficient mouse embryo fibroblasts. Our data demonstrate that RRM2B is induced by stress signals prior to the onset of senescence and prevents premature oxidative stress-induced senescence.
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影响因子：
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作者：
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通讯作者：
Rotig, Agnes
影响因子：
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作者：
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