Glucose metabolism induces mono-ubiquitination of histone H2B in mammalian cells
Glucose metabolism induces mono-ubiquitination of histone H2B in mammalian cells
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DOI：
10.1016/j.bbrc.2010.11.138
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发表时间：
2011-01-07
影响因子：
3.1
通讯作者：
Xu, C. Wilson
中科院分区：
文献类型：
--
作者：
Gao, Zhen;Xu, C. Wilson
组蛋白修饰在转录调控中起重要作用，并且与重要的生物学和疾病过程密切相关。尽管其功能的重要性，细胞外信号是否以及如何调节组蛋白修饰还没有很好的定义。使用组蛋白H2 B的单泛素化作为模型系统，我们先前已经证明组蛋白H2 B的单泛素化是由葡萄糖通过芽殖酵母酿酒酵母中的糖酵解诱导的[1]。由于组蛋白在真核生物中是非常保守的蛋白质，并且糖酵解是最保守的代谢途径，我们推断最初在酵母中发现的葡萄糖-糖酵解-uH 2B信号途径可能在人类细胞中是保守的。使用培养的人脑胶质瘤细胞作为模型，我们在这份报告中显示，细胞外介质调制的组蛋白H2 B在K120（uH 2B）的单泛素化的全球水平。营养剥夺去除了uH 2B的泛素部分。含葡萄糖的培养基在细胞中诱导uH 2B，而不含葡萄糖的培养基对uH 2B的诱导没有影响，表明葡萄糖是诱导uH 2B在细胞中所必需的。相反，非代谢性葡萄糖类似物在诱导uH 2B方面有缺陷，这表明在培养的胶质瘤细胞中葡萄糖诱导的单泛素化需要葡萄糖代谢。此外，PKM 2（恶性肿瘤中糖酵解的必需酶）的shRNA敲低抑制了这些细胞中组蛋白H2 B的单泛素化。综上所述，我们以前和现在的结果表明，新的葡萄糖-糖酵解-uH 2B信号通路是很好的保守从酵母到哺乳动物细胞，提供了一个进化上保守的组蛋白修饰的调节机制。(C)2010年爱思唯尔公司All rights reserved.
Histone modifications play an important role in transcriptional regulation and are intimately involved in important biological and disease processes. Despite their functional significance, whether and how extracellular signals modulate histone modifications are not well defined. Using mono-ubiquitination of histone H2B as a model system, we have previously shown that mono-ubiquitination of histone H2B is induced by glucose through glycolysis in budding yeast Sacchromyces cerevisiae [1]. Because histones are well conserved proteins among eukaryotes and glycolysis is the most conserved metabolic pathway, we reasoned that the glucose-glycolysis-uH2B signal pathway originally discovered in yeast may be conserved in human cells. Using cultured human glioma cells as a model, we show in this report that extracellular media modulated global levels of mono-ubiquitination of histone H2B at K120 (uH2B). Nutrient deprivation removed the ubiquitin moiety of uH2B. Glucose-containing media induced uH2B in the cells while media lacking glucose had no effect on the induction of uH2B, suggesting that glucose was required for inducing uH2B in the cells. In contrast, non-metabolic glucose analogs were defective in inducing uH2B, suggesting that glucose metabolism was required for glucose-induced mono-ubiquitination in the cultured glioma cells. Moreover, shRNA knockdown of PKM2, an essential enzyme for glycolysis in malignant tumors, inhibited mono-ubiquitination of histone H2B in these cells. Taken together, our previous and current results demonstrate that the novel glucose-glycolysis-uH2B signal pathway is well conserved from yeast to mammalian cells, providing an evolutionarily-conserved regulatory mechanism of histone modifications. (C) 2010 Elsevier Inc. All rights reserved.