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首页> 外文期刊>Molecular and Cellular Biology >The murine DUB-1 gene is specifically induced by the betac subunit of interleukin-3 receptor.
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The murine DUB-1 gene is specifically induced by the betac subunit of interleukin-3 receptor.

机译：鼠DUB-1基因是由白介素3受体的betac亚基特异性诱导的。

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Cytokines regulate cell growth and differentiation by inducing the expression of specific target genes. We have recently isolated a cytokine-inducible, immediate-early cDNA, DUB-1, that encodes a deubiquitinating enzyme. The DUB-1 mRNA was specifically induced by the receptors for interleukin-3, granulocyte-macrophage colony-stimulating factor, and interleukin-5, suggesting a role for the beta common (betac subunit known to be shared by these receptors. In order to identify the mechanism of cytokine induction, we isolated a murine genomic clone for DUB-1 containing a functional promoter region. The DUB-1 gene contains two exons, and the nucleotide sequence of its coding region is identical to the sequence of DUB-1 cDNA. Various regions of the 5' flanking region of the DUB-1 gene were assayed for cytokine-inducible activity. An enhancer region that retains the beta c-specific inducible activity of the DUB-1 gene was identified. Enhancer activity was localized to a 112-bp fragment located 1.4 kb upstream from the ATG start codon. Gel mobility shift assays revealed two specific protein complexes that bound to this minimal enhancer region. One complex was induced by betac signaling, while the other was noninducible. Finally, the membrane-proximal region of human betac was required for DUB-1 induction. In conclusion, DUB-1 is the first example of an immediate-early gene that is induced by a specific subunit of a cytokine receptor. Further analysis of the DUB-1 enhancer element may reveal specific determinants of a betac-specific signaling pathway.
机译：细胞因子通过诱导特定靶基因的表达来调节细胞的生长和分化。我们最近分离出了一种可诱导细胞因子诱导的立即早期cDNA DUB-1，它编码一种去泛素化酶。 DUB-1 mRNA是由白介素3，粒细胞巨噬细胞集落刺激因子和白介素5的受体特异性诱导的，提示了β共有（已知这些受体共有的betac亚基）的作用。为了确定细胞因子的诱导机制，我们为含有功能性启动子区的DUB-1分离了鼠类基因组克隆，DUB-1基因含有两个外显子，其编码区的核苷酸序列与DUB-1 cDNA的序列相同。测定了DUB-1基因5'侧翼区域的各个区域的细胞因子诱导活性，鉴定了保留了DUB-1基因的βc-特异性诱导活性的增强子区域。位于ATG起始密码子上游1.4 kb处的112 bp片段。凝胶迁移率变动分析揭示了两个与该最小增强子区域结合的特定蛋白质复合物。一种复合物是由betac信号传导诱导的，而另一种则不是诱导的。最后，DUB-1诱导需要人betac的膜近端区域。总之，DUB-1是由细胞因子受体的特定亚基诱导的早期基因的第一个例子。 DUB-1增强子元件的进一步分析可能会揭示betac特异性信号传导途径的特定决定因素。

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