Sodium butyrate-induced upregulation of p18INK4C gene affects K562 cell G0/G1 arrest and differentiation
Sodium butyrate-induced upregulation of p18INK4C gene affects K562 cell G0/G1 arrest and differentiation
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DOI：
10.1007/s11010-008-9870-x
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发表时间：
2008-12-01
影响因子：
4.3
通讯作者：
Lu, Jun
中科院分区：
文献类型：
--
作者：
Li, Lin;Zhang, Guoping;Lu, Jun
组蛋白脱乙酰酶抑制剂丁酸钠 (NaBu) 可诱导 K562 细胞中 G(0)/G(1) 阻滞和红系分化，但该过程背后的分子机制尚不清楚。在这里，我们发现在 NaBu 诱导的 K562 细胞红系分化过程中，p18(INK4C) mRNA 和蛋白质水平均上调。此外，NaBu 对 p18(INK4C) 的激活依赖于启动子中 Sp1 簇的完整性。 NaBu 引起内源性 p18(INK4C) 启动子上的组蛋白 H3 和 H4 过度乙酰化，并增强体内转录因子 Sp1 的结合。此外，K562 细胞中 p18(INK4C) 的过度表达导致 G(0)/G(1) 停滞和部分红系分化。我们的结果表明 NaBu 介导的 p18(INK4C) 调节在 K562 细胞的细胞周期停滞和红系分化中发挥作用。
Histone deacetylase inhibitor sodium butyrate (NaBu) can induce G(0)/G(1) arrest and erythroid differentiation in K562 cells, but the molecular mechanisms underlying this process are unclear. Here we show that both p18(INK4C) mRNA and protein levels were upregulated during K562 cell erythroid differentiation induced by NaBu. Moreover, the NaBu activation of p18(INK4C) was dependent on the integrity of Sp1 clusters in the promoter. NaBu caused hyperacetylation of histones H3 and H4 on endogenous p18(INK4C) promoter and enhanced binding of transcription factor Sp1 in vivo. Also, overexpression of p18(INK4C) in K562 cells resulted in G(0)/G(1) arrest and partial erythroid differentiation. Our results suggested that NaBumediated p18(INK4C) regulation played a role in cell cycle arrest and erythroid differentiation in K562 cells.