Kathrein Katie L, Lorenz Rachelle, Innes Angela Minniti, Griffiths Erin, Winandy Susan
Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, 320 E. Superior St., Morton 6-639, Chicago, IL 60611, USA.
Mol Cell Biol. 2005 Mar;25(5):1645-54. doi: 10.1128/MCB.25.5.1645-1654.2005.
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 G0/G1 stage of the cell cycle. This arrest is associated with up-regulation of the cell cycle-dependent kinase inhibitor p27kip1, 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.
Ikaros是一种造血细胞特异性锌指DNA结合蛋白，在淋巴细胞发育中起重要作用。Ikaros的基因破坏导致T细胞转化。Ikaros基因敲除小鼠会100%患白血病。据推测，Ikaros通过与染色质重塑复合物结合来控制基因表达。Ikaros基因敲除小鼠患白血病表明Ikaros具有肿瘤抑制基因的特征。在本报告中，我们表明将Ikaros导入已建立的小鼠Ikaros基因敲除T白血病细胞系会导致细胞周期在G0/G1期停滞。这种停滞与细胞周期依赖性激酶抑制剂p27kip1的上调、T细胞分化标志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细胞谱系真正肿瘤抑制基因的特性，并深入了解了Ikaros肿瘤抑制活性的机制。
