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首页> 外文期刊>Nature immunology >A small molecule Abl kinase inhibitor induces differentiation of Abelson virus-transformed pre-B cell lines.
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A small molecule Abl kinase inhibitor induces differentiation of Abelson virus-transformed pre-B cell lines.

机译:小分子Abl激酶抑制剂可诱导Abelson病毒转化的pre-B细胞系分化。

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摘要

Abelson murine leukemia virus-transformed cell lines have provided a critical model system for studying the regulation of B cell development. However, transformation by v-Abl blocks B cell development, resulting in the arrest of these transformants in an early pre-B cell-like state. We report here that treatment of Abelson virus-transformed pre-B cell lines with the small molecule Abl kinase inhibitor (STI571) results in their differentiation to a late pre-B cell-like state characterized by induction of immunoglobulin (Ig) light chain gene rearrangement. DNA microarray analyses enabled us to identify two genes inhibited by v-Abl that encode the Igk 3' enhancer-binding transcription factors Spi-B and IRF-4. We show that enforced expression of these two factors is sufficient to induce germline Igk transcription in Abelson-transformed pro-B cell lines. This suggests a key role for these factors, and perhaps for c-Abl itself, in the regulated activation of Ig light chain gene rearrangement.
机译:Abelson鼠白血病病毒转化的细胞系为研究B细胞发育的调控提供了关键模型系统。然而,通过v-Abl的转化阻止了B细胞的发育,导致这些转化子以早期的前B细胞样状态被阻滞。我们在此报告,用小分子Abl激酶抑制剂(STI571)治疗Abelson病毒转化的pre-B细胞系,导致其分化为以免疫球蛋白(Ig)轻链基因的诱导为特征的晚期pre-B细胞样状态重排。 DNA微阵列分析使我们能够鉴定出受v-Abl抑制的两个基因,这些基因编码Igk 3'增强子结合转录因子Spi-B和IRF-4。我们显示这两个因素的强制表达足以在Abelson转化的pro-B细胞系中诱导种系Igk转录。这表明这些因素,可能是c-Abl本身,在Ig轻链基因重排的调控激活中起着关键作用。

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