Histone demethylase Jumonji D3 (JMJD3) as a tumor suppressor by regulating p53 protein nuclear stabilization.
Histone demethylase Jumonji D3 (JMJD3) as a tumor suppressor by regulating p53 protein nuclear stabilization.
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DOI：
10.1371/journal.pone.0051407
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Fine HA
中科院分区：
文献类型：
--
作者：
Ene CI;Edwards L;Riddick G;Baysan M;Woolard K;Kotliarova S;Lai C;Belova G;Cam M;Walling J;Zhou M;Stevenson H;Kim HS;Killian K;Veenstra T;Bailey R;Song H;Zhang W;Fine HA
组蛋白甲基化通过组蛋白甲基转移酶和去甲基酶在谱系特定基因上的协调相互作用来调节正常干细胞的命运决定。恶性转化与抑制性组蛋白修饰的异常积累有关，如多梳介导组蛋白3赖氨酸27(H3K27me3)导致组蛋白甲基化介导的分化受阻。然而，组蛋白去甲基酶与癌症的相关性还不是很清楚。我们报道，JMJD3是一种H3K27me3去甲基酶，在胶质母细胞瘤干细胞(GSCs)分化过程中被诱导，它通过染色质依赖(Ink4a/ARF位点激活)和染色质非依赖(核P53蛋白稳定)机制促进分化样表型。我们的研究结果表明，JMJD3的失控可能通过抑制P53通路导致终末分化受阻而促进神经胶质瘤的发生。
Histone methylation regulates normal stem cell fate decisions through a coordinated interplay between histone methyltransferases and demethylases at lineage specific genes. Malignant transformation is associated with aberrant accumulation of repressive histone modifications, such as polycomb mediated histone 3 lysine 27 (H3K27me3) resulting in a histone methylation mediated block to differentiation. The relevance, however, of histone demethylases in cancer remains less clear. We report that JMJD3, a H3K27me3 demethylase, is induced during differentiation of glioblastoma stem cells (GSCs), where it promotes a differentiation-like phenotype via chromatin dependent (INK4A/ARF locus activation) and chromatin independent (nuclear p53 protein stabilization) mechanisms. Our findings indicate that deregulation of JMJD3 may contribute to gliomagenesis via inhibition of the p53 pathway resulting in a block to terminal differentiation.
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作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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