Ikaros induces quiescence and T-cell differentiation in a leukemia cell line
Ikaros induces quiescence and T-cell differentiation in a leukemia cell line
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DOI：
10.1128/mcb.25.5.1645-1654.2005
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发表时间：
2005-03-01
影响因子：
5.3
通讯作者：
Winandy, S
中科院分区：
文献类型：
--
作者：
Kathrein, KL;Lorenz, R;Winandy, S
Ikaros 是一种造血细胞特异性锌指 DNA 结合蛋白，在淋巴细胞发育中发挥重要作用。 Ikaros 的基因破坏导致 T 细胞转化。 Ikaros 缺失小鼠患白血病的外显率达 100%。据推测，Ikaros 通过与染色质重塑复合物的关联来控制基因表达。 Ikaros 缺失小鼠罹患白血病表明 Ikaros 具有抑癌基因的特征。在本报告中，我们表明将 Ikaros 引入已建立的小鼠 Ikaros null T 白血病细胞系会导致细胞周期的 G(0)/G(1) 阶段生长停滞。这种停滞与细胞周期依赖性激酶抑制剂 P27(kip1) 的上调、T 细胞分化标记物表达的诱导以及组蛋白 H3 乙酰化状态的整体和特异性增加有关。这些研究提供了强有力的证据，证明 Ikaros 具有 T 细胞谱系的真正肿瘤抑制基因的特性，并提供了对 Ikaros 肿瘤抑制活性机制的深入了解。
Ikaros is a hematopoietic cell-specific zinc finger DNA binding protein that plays an important role in lymphocyte development. Genetic disruption of Ikaros results in T-cell transformation. Ikaros null mice develop leukemia with 100% penetrance. It has been hypothesized that Ikaros controls gene expression through its association with chromatin remodeling complexes. The development of leukemia in Ikaros null mice suggests that Ikaros has the characteristics of a tumor suppressor gene. In this report, we show that the introduction of Ikaros into an established mouse Ikaros null T leukemia cell line leads to growth arrest at the G(0)/G(1) stage of the cell cycle. This arrest is associated with up-regulation of the cell cycle-dependent kinase inhibitor P27(kip1), the induction of expression of T-cell differentiation markers, and a global and specific increase in histone H3 acetylation status. These studies provide strong evidence that Ikaros possesses the properties of a bona fide tumor suppressor gene for the T-cell lineage and offer insight into the mechanism of Ikaros's tumor suppressive activity.