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首页> 外文期刊>Molecular and Cellular Biology >mcl-1 Is an Immediate-Early Gene Activated by the Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Signaling Pathway and Is One Component of the GM-CSF Viability Response
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mcl-1 Is an Immediate-Early Gene Activated by the Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Signaling Pathway and Is One Component of the GM-CSF Viability Response

机译：mcl-1是由粒细胞-巨噬细胞集落刺激因子（GM-CSF）信号通路激活的立即早期基因，并且是GM-CSF活力反应的一个组成部分

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mcl-1, a bcl-2 family member, was originally identified as an early gene induced during differentiation of ML-1 myeloid leukemia cells. In the present study, we demonstrate that Mcl-1 is tightly regulated by the granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling pathway. Upon deprivation of survival factor from TF-1 myeloid progenitor cells, Mcl-1 levels quickly dropped prior to visible detection of apoptosis of these cells. Upon restimulation of these deprived cells with GM-CSF, themcl-1 mRNA was immediately induced and its protein product was accordingly resynthesized. Analysis with Ba/F3 cells expressing various truncation mutants of the GM-CSF receptor revealed that the membrane distal region between amino acids 573 and 755 of the receptor β chain was required for mcl-1 induction. Transient-transfection assays with luciferase reporter genes driven by various regions of the mcl-1 promoter demonstrated that the upstream sequence between ?197 and ?69 is responsible for cytokine activation of the mcl-1 gene. Overexpression ofmcl-1 delayed but did not completely prevent apoptosis of cells triggered by cytokine withdrawal. Its down regulation by antisense constructs overcame, at least partially, the survival activity of GM-CSF and induced the apoptosis of TF-1 cells. Taken together, these results suggest that mcl-1 is an immediate-early gene activated by the cytokine receptor signaling pathway and is one component of the GM-CSF viability response.
机译： mcl-1 ， bcl-2 家族成员，最初被鉴定为在ML-1髓样白血病细胞分化过程中诱导的早期基因。在本研究中，我们证明了Mcl-1受到粒细胞-巨噬细胞集落刺激因子（GM-CSF）信号通路的严格调控。从TF-1髓样祖细胞中剥夺生存因子后，Mcl-1水平迅速下降，然后可见这些细胞的凋亡。用GM-CSF重新刺激这些被剥夺的细胞后，立即诱导 mcl-1 mRNA并相应地重新合成其蛋白质产物。对表达各种GM-CSF受体截短突变体的Ba / F3细胞的分析表明， mcl-1 诱导需要受体β链氨基酸573和755之间的膜远端区域。由 mcl-1 启动子的各个区域驱动的荧光素酶报道基因的瞬时转染试验表明，？197和？69之间的上游序列负责 mcl-1 < / em>基因。 mcl-1 的过表达延迟但不能完全阻止细胞因子撤药触发的细胞凋亡。其反义构建体的下调至少部分克服了GM-CSF的存活活性并诱导了TF-1细胞的凋亡。综上所述，这些结果表明 mcl-1 是一种由细胞因子受体信号传导途径激活的立即早期基因，并且是GM-CSF生存力反应的一个组成部分。

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