A factor induced by differentiation signals in cells of the macrophage lineage binds to the gamma interferon activation site

A factor induced by differentiation signals in cells of the macrophage lineage binds to the gamma interferon activation site
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巨噬细胞谱系细胞中分化信号诱导的因子与γ干扰素激活位点结合

DOI:
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发表时间:
1994
影响因子:
5.3
通讯作者:
'. Decker
'. Decker
中科院分区:
生物学2区
文献类型:
--
作者:
Andreas Eilers;Manuela Baccarini;Friedemann Horn;R. Hipskind;C. Schindler;Thomas;'. Decker

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γ干扰素(ifn - γ)应答基因的快速转录诱导是由ifn - γ激活位点(GAS)及其同源蛋白ifn - γ激活因子(GAF)介导的。我们将气体相关的分化诱导因子(DIF)描述为ifn - γ活性与生长和分化因子之间的潜在分子联系。小鼠巨噬细胞中的DIF DNA结合可被集落刺激因子1激活,在髓系U937细胞中,也可在醋酸十四烷醇酚诱导分化或ifn - γ处理时被激活。ifn - γ的激活在单核细胞分化时显著降低。抗磷酸酪氨酸抗体可抑制DIF与DNA的结合,钒酸盐可诱导DIF与U937细胞结合。与GAF不同,DIF-DNA复合物不含有ISGF-3的91-kDa蛋白(p91)。DIF与ifp53 /色氨酸- trna合成酶和Fc γ γ RI基因启动子的GAS具有高亲和力,与Ly6A/E GAS具有中等亲和力,与鸟苷结合蛋白GAS具有低亲和力。DIF可能属于细胞因子或生长因子诱导的因子家族,与GAS相关元件的结合具有不同的亲和力:与不同ifn诱导启动子的GAS相关的白介素-6应答急性期反应因子,但与DIF相比具有不同的结合偏好。c-fos启动子的单链诱导元件结合GAF而不结合DIF。然而,可以通过点突变改变诱导因子来竞争GAF和DIF的结合。我们的数据显示DIF是一种新的dna结合蛋白,它在响应分化信号时被激活。此外,他们认为细胞因子或生长因子调节蛋白家族通过结合gas相关元件整合和协调对细胞因子和生长分化因子的反应。
Rapid transcriptional induction of genes in response to gamma interferon (IFN-gamma) is mediated by the IFN-gamma activation site (GAS) and its cognate protein, the IFN-gamma activation factor (GAF). We describe a GAS-associated, differentiation-induced factor (DIF) as a potential molecular link between the activities of IFN-gamma and of growth and differentiation factors. DIF DNA binding was activated by colony-stimulating factor 1 in murine macrophages and also during tetradecanoyl phorbol acetate-induced differentiation or IFN-gamma treatment in myeloid U937 cells. IFN-gamma activation of DIF decreased significantly upon monocytic differentiation. DIF binding to DNA was inhibited by antiphosphotyrosine antibodies and could be induced by treatment of U937 cells with vanadate. Unlike GAF, DIF-DNA complexes did not contain the 91-kDa protein (p91) from ISGF-3. DIF bound with high affinity to GAS from the promoters of the IFP 53/tryptophanyl-tRNA synthetase and Fc gamma RI genes, intermediate affinity to the Ly6A/E GAS, and low affinity to the guanylate-binding protein GAS. DIF may belong to a family of cytokine- or growth factor-induced factors binding with variable affinities to GAS-related elements: the interleukin-6-responsive acute-phase response factor associated with GAS from different IFN-inducible promoters but with a different preference of binding compared with DIF. The sis-inducible element of the c-fos promoter bound GAF but not DIF. However, the sis-inducible element could be changed by point mutation to compete for GAF and DIF binding. Our data show DIF to be a novel DNA-binding protein which is activated in response to differentiating signals. Moreover, they suggest that a family of cytokine- or growth factor-regulated proteins integrates and coordinates the responses to cytokines and to growth and differentiation factors by binding to GAS-related elements.
DOI: 10.1126/science.7690989
发表时间: 1993-09-24
期刊: SCIENCE
影响因子: 56.9
作者:
SHUAI, K;STARK, GR;DARNELL, JE
通讯作者: DARNELL, JE
DOI: --
发表时间: 1992-09
影响因子: 2.6
作者:
Mu-Ya Liu;Ming-Chi Wu
通讯作者: Mu-Ya Liu;Ming-Chi Wu
DOI: 10.1101/gad.4.10.1753
发表时间: 1990-10-01
影响因子: 10.5
作者:
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通讯作者: LEVY, DE
DOI: 10.1073/pnas.84.18.6394
发表时间: 1987-09-01
影响因子: 11.1
作者:
REICH, N;EVANS, B;DARNELL, JE
通讯作者: DARNELL, JE