Bach1 inhibits oxidative stress-induced cellular senescence by impeding p53 function on chromatin
Bach1 inhibits oxidative stress-induced cellular senescence by impeding p53 function on chromatin
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DOI：
10.1038/nsmb.1516
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发表时间：
2008-12-01
影响因子：
16.8
通讯作者：
Igarashi, Kazuhiko
中科院分区：
文献类型：
--
作者：
Dohi, Yoshihiro;Ikura, Tsuyoshi;Igarashi, Kazuhiko
细胞衰老是抑制突变细胞扩张的关键策略之一。衰老是对遗传毒性和氧化应激的反应。在这里，我们证明了转录因子Bach1(BTB和Cnc同源1，碱性亮氨酸拉链转录因子1)，它抑制氧化应激诱导基因，是氧化应激诱导细胞衰老的关键负调控因子。与对照野生型细胞相比，Bach1基因缺陷的小鼠胚胎成纤维细胞在氧化应激下表现出更快和更严重的依赖于P53的提前衰老的倾向。Bach1形成一个包含P53、组蛋白脱乙酰酶1和核共抑制物N-COR的复合体。Bach1被招募到P53靶基因的一个子集，并通过促进组蛋白去乙酰化来阻止P53的作用。由于Bach1受氧化应激和血红素的调节，我们的数据表明Bach1作为P53的负调节因子将氧代谢和细胞衰老联系在一起。
Cellular senescence is one of the key strategies to suppress expansion of cells with mutations. Senescence is induced in response to genotoxic and oxidative stress. Here we show that the transcription factor Bach1 (BTB and CNC homology 1, basic leucine zipper transcription factor 1), which inhibits oxidative stress-inducible genes, is a crucial negative regulator of oxidative stress induced cellular senescence. Bach1-deficient murine embryonic fibroblasts showed a propensity to undergo more rapid and profound p53-dependent premature senescence than control wild-type cells in response to oxidative stress. Bach1 formed a complex that contained p53, histone deacetylase 1 and nuclear co-repressor N-coR. Bach1 was recruited to a subset of p53 target genes and contributed to impeding p53 action by promoting histone deacetylation. Because Bach1 is regulated by oxidative stress and heme, our data show that Bach1 connects oxygen metabolism and cellular senescence as a negative regulator of p53.