Opposing actions of c-ets/PU.1 and c-myb protooncogene products in regulating the macrophage-specific promoters of the human and mouse colony-stimulating factor-1 receptor (c-fms) genes.

Opposing actions of c-ets/PU.1 and c-myb protooncogene products in regulating the macrophage-specific promoters of the human and mouse colony-stimulating factor-1 receptor (c-fms) genes.
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C-ETS/PU.1和C-MYB原子能产品在调节人和小鼠菌落刺激因子1受体(C-FMS)基因的巨噬细胞特异性启动子方面的相对作用。

DOI:
10.1084/jem.180.6.2309
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发表时间:
1994-12-01
影响因子:
15.3
通讯作者:
Ostrowski, Michael C.
Ostrowski, Michael C.
中科院分区:
医学1区
文献类型:
--
作者:
Reddy, M. Amarender;Yang, Beom-Seok;Yue, Xie;Barnett, Christopher J. K.;Ross, Ian L.;Sweet, Matthew J.;Hume, David A.;Ostrowski, Michael C.

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巨噬细胞集落刺激因子受体(CSF-1)是c-FMS基因产物,是单核细胞吞噬细胞分化的关键决定因素。对人类和小鼠c-fms近端启动子的剖析揭示了核原癌基因在该基因转录调控中的相反作用。一方面,c-ETS-1、c-ETS-2和巨噬细胞特异性因子PU.1反式激活c-FMS近端启动子,而不是ETS-PEA3。另一方面,c-myb抑制巨噬细胞近端启动子活性,阻断c-ETS-1和c-ETS-2的作用。在高表达c-myb的M1白血病株中几乎检测不到基本的c-fms启动子活性,但当白血病抑制因子诱导分化的细胞表达c-fms mRNA时,c-fms启动子活性被激活。C-myb的抑制功能依赖于该蛋白的COOH-末端结构域。我们认为,Ets因子对于c-fms的组织限制性表达是必需的,c-myb在髓系分化过程中确保c-fms的正确时间表达。
The receptor for macrophage colony stimulating factor (CSF-1), the c- fms gene product, is a key determinant in the differentiation of monocytic phagocytes. Dissection of the human and mouse c-fms proximal promoters revealed opposing roles for nuclear protooncogenes in the transcriptional regulation of this gene. On the one hand, c-ets-1, c- ets-2, and the macrophage-specific factor PU.1, but not the ets-factor PEA3, trans-activated the c-fms proximal promoter. On the other hand c- myb repressed proximal promoter activity in macrophages and blocked the action of c-ets-1 and c-ets-2. Basal c-fms promoter activity was almost undetectable in the M1 leukaemia line, which expressed high levels of c- myb, but was activated as cells differentiated in response to leukemia inhibitory factor and expressed c-fms mRNA. The repressor function of c- myb depended on the COOH-terminal domain of the protein. We propose that ets-factors are necessary for the tissue-restricted expression of c-fms and that c-myb acts to ensure correct temporal expression of c- fms during myeloid differentiation.
DOI: 10.1038/335835a0
发表时间: 1988-10-27
期刊: NATURE
影响因子: 64.8
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发表时间: 1992-02-15
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发表时间: 1988-05-01
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