期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 25, 期 5, 页码 1645-1654出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.25.5.1645-1654.2005
关键词
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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.
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