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首页> 外文期刊>Molecular and Cellular Biology >Functional and physical associations between NF-kappa B and C/EBP family members: a Rel domain-bZIP interaction.
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Functional and physical associations between NF-kappa B and C/EBP family members: a Rel domain-bZIP interaction.

机译:NF-κB和C / EBP家族成员之间的功能和物理关联:Rel域-bZIP相互作用。

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NF-kappa B and C/EBP represent distinct families of transcription factors that target unique DNA enhancer elements. The heterodimeric NF-kappa B complex is composed of two subunits, a 50- and a 65-kDa protein. All members of the NF-kappa B family, including the product of the proto-oncogene c-rel, are characterized by their highly homologous approximately 300-amino-acid N-terminal region. This Rel homology domain mediates DNA binding, dimerization, and nuclear targeting of these proteins. C/EBP contains the bZIP region, which is characterized by two motifs in the C-terminal half of the protein: a basic region involved in DNA binding and a leucine zipper motif involved in dimerization. The C/EBP family consist of several related proteins, C/EBP alpha, C/EBP beta, C/EBP gamma, and C/EBP delta, that form homodimers and that form heterodimers with each other. We now demonstrated the unexpected cross-coupling of members of the NF-kappa B family three members of the C/EBP family. NF-kappa B p65, p50, and Rel functionally synergize with C/EBP alpha, C/EBP beta, and C/EBP delta. This cross-coupling results in the inhibition of promoters with kappa B enhancer motifs and in the synergistic stimulation of promoters with C/EBP binding sites. These studies demonstrate that NF-kappa B augments gene expression mediated by a multimerized c-fos serum response element in the presence of C/EBP. We show a direct physical association of the bZIP region of C/EBP with the Rel homology domain of NF-kappa B. The cross-coupling of NF-kappa B with C/EBP highlights a mechanism of gene regulation involving an interaction between distinct transcription factor families.
机译:NF-κB和C / EBP代表着独特的DNA增强子元件的转录因子家族。异二聚体NF-κB复合物由两个亚基组成,一个是50 kDa的蛋白质,另一个是65 kDa的蛋白质。 NF-κB家族的所有成员,包括原癌基因c-rel的产物,都具有高度同源的大约300个氨基酸的N端区域。该Rel同源域介导这些蛋白质的DNA结合,二聚化和核靶向。 C / EBP包含bZIP区域,其特征在于蛋白质C端一半的两个基序:一个参与DNA结合的基本区域和一个参与二聚化的亮氨酸拉链基序。 C / EBP家族由几种相关的蛋白质组成,即C / EBPα,C / EBP beta,C / EBPγ和C / EBPδ,它们形成同二聚体并彼此形成异二聚体。现在,我们证明了NF-κB家族成员与C / EBP家族的三个成员之间的意外交叉耦合。 NF-κB p65,p50和Rel在功能上与C / EBP alpha,C / EBP beta和C / EBP delta协同作用。这种交叉偶联导致抑制具有κB增强子基序的启动子,并协同刺激具有C / EBP结合位点的启动子。这些研究表明,在C / EBP存在的情况下,NF-κB增强了由多聚c-fos血清反应元件介导的基因表达。我们显示了C / EBP的bZIP区与NF-κB的Rel同源域的直接物理关联。NF/κB与C / EBP的交叉偶联突出了涉及不同转录之间相互作用的基因调控机制因素家庭。

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