Hes1 expression and CYLD repression are essential events downstream of Notch1 in T-cell leukemia
Hes1 expression and CYLD repression are essential events downstream of Notch1 in T-cell leukemia
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DOI：
10.4161/cc.10.7.15067
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发表时间：
2011-04-01
期刊：
影响因子：
4.3
通讯作者：
Bigas, Anna
中科院分区：
文献类型：
--
作者：
D'Altri, Teresa;Gonzalez, Jessica;Bigas, Anna
Notch激活是T急性淋巴细胞白血病（T-ALL）中的一个当前事件，但能够支持Notch依赖性白血病的下游元件尚未得到很好的表征。我们最近发现Notch-Hes 1-CYLD-NF κ B轴在T-ALL的维持中是至关重要的，但是对这些元件中的每一个的贡献的详细评估仍然缺失。在这里，我们使用Notch 1诱导的白血病体内模型来研究沉默Notch靶基因Hes 1或过表达Hes 1靶基因CYLD的效果。我们在这里表明，这两种策略完全消除了组成型活性Notch 1产生T-ALL的能力。
Notch activation is a current event in T Acute Lymphoblastic Leukemia (T-ALL) but the downstream elements that are able to support Notch-dependent leukemias are not well characterized. We have recently shown that the Notch-Hes1-CYLD-NF kappa B axis is crucial in the maintenance of T-ALL, but detailed evaluation of the contribution of each one of these elements is still missing. Here we use a Notch1-induced leukemia in vivo model to study the effect of silencing the Notch-target gene, Hes1 or overexpressing the Hes1-target, CYLD. We here show that both strategies completely abolish the ability of constitutive active Notch1 to generate T-ALL.