Characterization of A1, a novel hemopoietic-specific early-response gene with sequence similarity to bcl-2.
Characterization of A1, a novel hemopoietic-specific early-response gene with sequence similarity to bcl-2.
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DOI：
10.4049/jimmunol.151.4.1979
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发表时间：
1993-08
影响因子：
4.4
通讯作者：
E. Lin;A. Orlofsky;M. Berger;M. Prystowsky
中科院分区：
文献类型：
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作者：
E. Lin;A. Orlofsky;M. Berger;M. Prystowsky
粒细胞-巨噬细胞集落刺激因子（GM-CSF）通过诱导特定基因的表达来刺激造血细胞增殖、分化和功能活化。作为GM-CSF基因表达调控研究的一部分，我们以前已经确定了一个新的小鼠GM-CSF诱导基因，A1。在这份报告中，我们提出了完整的核苷酸序列的A1 mRNA以及部分的5'侧翼区，并描述了基因的表达模式。结果表明，A1是一个造血组织特异性基因，表达在几个造血细胞谱系，包括T辅助淋巴细胞，巨噬细胞和中性粒细胞。在小鼠骨髓源性巨噬细胞中，A1基因表达被GM-CSF快速且瞬时地诱导，并且该诱导不依赖于从头蛋白质合成。除GM-CSF外，在巨噬细胞中观察到响应于LPS的A1 mRNA积累的瞬时诱导。这种诱导不是由IL-1 α或IL-6介导的，它们都不刺激A1。在髓样前体细胞系中，32 D cl 3，A1基因表达在粒细胞集落刺激因子刺激的髓样细胞分化期间被稳定诱导。A1信息编码预测的多肽，其M（r）为20，024，并且没有信号肽。该肽序列包含一个80个氨基酸的区域，该区域与bcl-2和最近描述的bcl-2相关基因MCL 1相似。这些数据表明，A1是一种新的早期反应基因，其表达与各种刺激有关，并发生在几种造血细胞类型。
Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates hemopoietic cell proliferation, differentiation, and functional activation by inducing the expression of specific genes. As part of an investigation of the regulation of gene expression by GM-CSF, we have previously identified a novel murine GM-CSF-inducible gene, A1. In this report, we present the complete nucleotide sequence of the A1 mRNA as well as a portion of the 5' flanking region, and describe the expression pattern of the gene. The results demonstrate that A1 is a hemopoietic tissue-specific gene that is expressed in several hemopoietic cell lineages, including T-helper lymphocytes, macrophages, and neutrophils. In murine bone marrow-derived macrophages, A1 gene expression is rapidly and transiently induced by GM-CSF, and the induction was independent of de novo protein synthesis. In addition to GM-CSF, a transient induction of A1 mRNA accumulation was observed in response to LPS in macrophages. This induction is not mediated by IL-1 alpha or IL-6, neither of which stimulate A1. In the myeloid precursor cell line, 32D cl3, A1 gene expression is stably induced during granulocyte colony-stimulating factor-stimulated myeloid cell differentiation. The A1 message encodes a predicted polypeptide with an M(r) of 20,024 and no signal peptide. The peptide sequence contains a region of 80 amino acids that shows similarity to bcl-2 and to the recently described bcl-2-related gene, MCL1. These data demonstrate that A1 is a novel early-response gene whose expression is associated with a variety of stimuli and occurs in several hemopoietic cell types.